aq: aqueous;; Boc: tert butyloxycarbonyl; DCM: dichloromethane; br: broad; d:

Size: px
Start display at page:

Download "aq: aqueous;; Boc: tert butyloxycarbonyl; DCM: dichloromethane; br: broad; d:"

Transcription

1 SUPPLEMENTARY NOTE Synthetic Procedures Abbreviations and Acronyms aq: aqueous;; Boc: tert butyloxycarbonyl; DCM: dichloromethane; br: broad; d: doublet; DIPEA: diisopropylethylamine; DME: dimethoxyethane; DMF: N,Ndimethylformamide; DMSO: dimethylsulfoxide; EDC: N ( dimethylaminopropyl) N ethylcarbodiimide hydrochloride; EtOAc: ethyl acetate; PE: petroleum ether 0/0; ee: enantiomeric excess; ESI: electrospray ionization; h: hour; HATU: N [(dimethylamino) 1H 1,, triazolo [, b]pyridin 1 ylmethylene] Nmethylmethanaminium hexafluorophosphate N oxide; HPLC: high pressure liquid chromatography; LC: liquid chromatography; LCMS: liquid chromatography mass spectrometry; M: molar; m/z: mass to charge ratio; MeCN: acetonitrile; MeOH: methanol; min: minutes; MS: mass spectrometry; m: multiplet; NMR: nuclear magnetic resonance; q: quartet; quint: quintet; R T : retention time; RT: room temperature; s: singlet; SPhos: dicyclohexylphosphino, dimethoxybiphenyl; TFA: trifluoroacetic acid; THF: tetrahydrofuran; t: triplet; v/v: volume per unit volume; Walphos SL W00 :(S) 1 {(S P ) [ (dicyclohexylphosphino)phenyl]ferrocenyl}ethylbis[, bis(trifluoromethyl)phenyl]phosphine; 1 0 General Experimental Conditions 1 Solvents and reagents Page 1 of 1 Nature Chemical Biology: doi:./nchembio.

2 Common organic solvents that were used in reactions (e.g. THF, DMF, DCM, and methanol) were purchased anhydrous from Sigma Aldrich in Sure/Seal TM bottles and were handled appropriately under nitrogen. Water was deionised using an Elga PURELAB Option Q. All other solvents used (i.e. for work up procedures and purification) were generally HPLC grade and were used as supplied from various commercial sources. Unless otherwise stated, all starting materials used were purchased from commercial suppliers and used as supplied. Microwave synthesis Microwave experiments were carried out using a Biotage Initiator Eight system. Flash chromatography Purification of compounds by flash chromatography was achieved using a Biotage Isolera Four system using the stated cartridges NMR spectroscopy 1 H NMR spectra were recorded at ambient temperature using a Bruker Avance (00 MHz), Bruker Avance III (00 MHz) or Bruker Ascend (00 MHz) spectrometer. All chemical shifts (δ) are expressed in ppm. Residual solvent signals were used as an internal standard and the characteristic solvent peaks were corrected to the reference data outlined in J. Org. Chem., 1,, p ; in other cases, NMR solvents contained tetramethylsilane, which was used as an internal standard. Liquid Chromatography Mass Spectrometry (LCMS) Page of 1 Nature Chemical Biology: doi:./nchembio.

3 Liquid Chromatography Mass Spectrometry (LCMS) experiments to determine retention times (R T ) and associated mass ions were performed using the following methods: Method A: The system consisted of an Agilent Technologies 0 quadrupole mass spectrometer linked to an Agilent Technologies 0 Infinity LC system with UV diode array detector and autosampler. The spectrometer consisted of an electrospray ionization source operating in positive and negative ion mode. LCMS experiments were performed on each sample submitted using the following conditions: LC Column: Agilent Eclipse Plus C1 RRHD, 1. µm, 0 x.1 mm maintained at 0 C. Mobile phases: A) 0.1% (v/v) formic acid in water; B) 0.1% (v/v) formic acid in acetonitrile. Gradient Time (min) Flow (ml/min) %A %B Method B: The system consisted of an Agilent Technologies 0 single quadrupole mass spectrometer linked to an Agilent Technologies 0 Infinity LC system with UV diode array detector and autosampler. The spectrometer consisted of a multimode ionization source (electrospray and atmospheric pressure chemical ionizations) Page of 1 Nature Chemical Biology: doi:./nchembio.

4 operating in positive and negative ion mode. LCMS experiments were performed on each sample submitted using the following conditions: LC Column: Zorbax Eclipse Plus C1 RRHD, 1. µm, 0 x.1 mm maintained at 0 C. Mobile phases: A) 0.1% (v/v) formic acid in water; B) 0.1% (v/v) formic acid in acetonitrile. Gradient Time (min) Flow (ml/min) %A %B Nomenclature Unless otherwise indicated, the nomenclature of structures was determined using the Convert Structure to Name function of ChemBioDraw Ultra.0. (CambridgeSoft/PerkinElmer). Compound 1 Br S O N N OH N O Step 1: 1 ( Phenylpropanoyl)piperidin one ():: Page of 1 Nature Chemical Biology: doi:./nchembio.

5 1 1 1 A solution of tert butyl oxopiperidine 1 carboxylate ( g,.1 mmol) in DCM ( ml) and TFA (. ml, mmol) was stirred at RT for h before the solvent was removed in vacuo and the product dried under high vacuum. To a stirred suspension of the TFA salt in dry DCM ( ml) was added DIPEA (. ml,.0 mmol) before phenylpropanoic acid (. g, 0.1 mmol), EDC (. g,. mmol) and DMAP (0.0 g,.1 mmol) were added. The reaction mixture was stirred at RT for 1 h, diluted with DCM (0 ml) and washed with saturated NaHCO (aq) (0 ml). The aqueous layer was further extracted with DCM ( ml) before the combined organic phases were washed with % HCl (aq) (0 ml) and brine (0 ml). The combined organic phases were passed through a Biotage phase separator, concentrated in vacuo and purified by flash chromatography (Biotage KP Sil 0 g cartridge, 0 0% EtOAc in PE) to give the title compound as pale yellow oil. LCMS (Method A): R T = 0. min, m/z = [M+H] +. 1 H NMR (00 MHz, CDCl ): δ.. (m, H),. (t, J =. Hz, H),. (t, J =. Hz, H),.0 (dd, J =.,. Hz, H),. (dd, J =.,. Hz, H),. (t, J =. Hz, H),. (t, J =. Hz, H). C NMR ( MHz, CDCl ): δ 0., 11., 1.0,.1,.,.1,., 1., 0., 0.,.01, Step : Phenyl 1 (1 oxa azaspiro[.]octan yl)propan 1 one (): 1 Page of 1 Nature Chemical Biology: doi:./nchembio.

6 To a solution of trimethylsulfonium iodide (. g,. mmol) in dry DMSO (0 ml) was added a 0% dispersion of NaH in mineral oil (0. g,. mmol). The resulting mixture was stirred at RT for 1 h before a solution of 1 ( phenylpropanoyl)piperidin one (.0 g,. mmol) in dry DMSO ( ml) was added. The reaction mixture was stirred at 0 C for h before it was allowed to cool to RT and quenched by the addition of water (0 ml). The resulting mixture was extracted with Et O ( x 0 ml), the combined organic extracts were washed with brine, dried over Na SO, concentrated in vacuo, and the product was purified by flash chromatography (Biotage KP Sil 0 g cartridge, 0 0% EtOAc in PE) to give the title compound (1.1 g, %) as a colourless oil. LCMS (Method A): R T = 1.0 min, m/z = [M+H] +. 1 H NMR (00 MHz, CDCl ): δ..0 (m, H),.1.0 (m, 1H),.0. (m, 1H),. (tdd, J =.,.0,. Hz, H),.0. (m, H),.. (m, H), 1.1 (ddd, J =.,.0,. Hz, 1H), 1. (ddd, J =.,.1,. Hz, 1H), (m, H). C NMR ( MHz, CDCl ): δ 10., 1.,.,.,.,.0,.,., 0.,.,.,., Step : Bromo (( hydroxy 1 ( phenylpropanoyl)piperidin yl)methyl)thieno[, d]pyrimidin (H) one (1): A mixture of phenyl 1 (1 oxa azaspiro[.]octan yl)propan 1 one (0 mg, 0.0 mmol), bromothieno[, d]pyrimidin (H) one 1 (1 mg, 0. mmol) and Cs CO ( mg, 0.1 mmol) in DMF ( ml) was heated at 0 C for 1 h. Upon cooling Page of 1 Nature Chemical Biology: doi:./nchembio.

7 to RT, the mixture was diluted with saturated NH Cl (aq) (0 ml) and extracted with DCM ( x 0 ml) using a Biotage phase separator. The combined organic phases were concentrated in vacuo and the residue was purified by flash chromatography (Biotage KP NH g cartridge, 0 0% MeOH in DCM) to give the title compound (0 mg, %) as a colourless solid. LCMS (Method A): R T = 1. min (purity >% at nm), m/z =, [M+H] +. 1 H NMR (00 MHz, DMSO d ): δ. (s, H),.. (m, H),. (s, 1H),..0 (m, 1H),.0. (m, H),.. (m, 1H),..1 (m, 1H),.. (m, 1H),.0 (t, J =. Hz, H),.. (m, H), (m, H). C NMR ( MHz, DMSO d ): δ 1.,.,.0, 1., 1.,.,.,.1,., 1.,.0,.1,., 0.,.,.,.,., 0.. HRMS (TOF MS ES+): m/z [M + H] + Calcd for C 1 H N O SBr.0, found.0. Compound Step 1: tert Butyl (( bromo oxothieno[, d]pyrimidin (H) yl)methyl) hydroxypiperidine 1 carboxylate ():: 1 Page of 1 Nature Chemical Biology: doi:./nchembio.

8 A mixture of tert butyl 1 oxa azaspiro[.]octane carboxylate (0 mg,.00 mmol), bromothieno[, d]pyrimidin (H) one 1 ( mg,.0 mmol) and Cs CO ( mg,.00 mmol) in DMF (. ml) was heated at 0 C for 1 h. Upon cooling to RT, the mixture was diluted with saturated NH Cl (aq) (0 ml) and extracted with DCM ( x 0 ml) using a Biotage phase separator. The combined organic phases were concentrated in vacuo and the residue was purified by flash chromatography (GraceResolv silica 0 g cartridge, 0 0% EtOAc in cyclohexane) to give the title compound ( mg, %) as a pale yellow solid. LCMS (Method A): R T = 1.1 min, m/z =, [M+Na] +. 1 H NMR (00 MHz, DMSO d ): δ.0 (s, H),. (s, 1H),.. (m, H),.. (m, H),..1 (m, H), (m, H), 1. (s, H). C NMR ( MHz, CDCl ): δ.,.,.01,.1, 1.,.,.,.0, 0.,.0,.,.,.. Step : Bromo (( hydroxypiperidin yl)methyl)thieno[, d]pyrimidin (H) one (): A solution of tert butyl (( bromo oxothieno[, d]pyrimidin (H) yl)methyl) hydroxypiperidine 1 carboxylate (0 mg, 0. mmol) was stirred in DCM ( ml) and TFA ( ml) for 0 min before the reaction was purified using a g SCX cartridge (% MeOH in DCM then 0% M NH in MeOH in DCM) to give the title compound (1 mg, %) as a colourless solid. LCMS (Method A): R T = 0. min, m/z =, [M+H] +. 1 H NMR (00 MHz, CDCl ): δ.0 (s, 1H),. (s, 1H),. (s, H),.. Page of 1 Nature Chemical Biology: doi:./nchembio.

9 (m, H), (m, H), (m, H). C NMR (1 MHz, CDCl ): δ.0,.0, 0.0, 1.,.0,., 0.,.0,.0,.0. Step : (R) Bromo (( hydroxy 1 ( phenylbutanoyl)piperidin yl)methyl)thieno[, d]pyrimidin (H) one (): DIPEA (0. ml,.0 mmol) was added to a suspension of bromo (( hydroxypiperidin yl)methyl)thieno[, d]pyrimidin (H) one (1 mg, 0. mmol), (R) phenylbutanoic acid (1 mg, 0.1 mmol) and HATU ( mg, 0.1 mmol) in DCM (. ml). After min, the reaction was quenched by the addition of saturated NaHCO (aq) (0 ml) and the mixture was extracted with DCM ( x 0 ml) using a Biotage phase separator. The combined organic phases were concentrated in vacuo and the residue was purified by flash chromatography (GraceResolv silica 0 g cartridge, 0 0% EtOAc in cyclohexane then 0 0% MeOH in EtOAc) to give the title compound ( mg, %) as a colourless solid. LCMS (Method A): R T = 1. min (purity >% at nm), m/z = 0, [M+H] +. 1 H NMR (00 MHz, DMSO d ): δ..1 (m, H),..0 (m, H),.00. (m, 1H),.. (m, H),.1. (m, 1H),..0 (m, H),.1. (m, 1H),.. (m, H), (m, H). C NMR ( MHz, DMSO d ): δ (conformers),. +. (conformers),., (conformers),. +. (conformers),.,.1 +. (conformers),. +. (conformers),. +. Page of 1 Nature Chemical Biology: doi:./nchembio.

10 (conformers), 1.,.0,.0 +. (conformers),.1, (conformers), (conformers),.,.1 +. (conformers),. +.0 (conformers),. +. (conformers), (conformers). HRMS (TOF MS ES+): m/z [M + H] + Calcd for C H N O SBr 0.000, found 0.0. Compound (ent ) Compound ent was made by an identical method as starting from Bromo (( hydroxypiperidin yl)methyl)thieno[, d]pyrimidin (H) one but using (S) phenylbutanoic acid in the coupling step. Compound Step 1: Bromo methyl H pyrazolo[, d]pyrimidin (H) one (): Bromine (. ml,. mmol) was added to a suspension of methyl H pyrazolo[, d]pyrimidin (H) one (. g, 1. mmol) in AcOH (1. ml) in a reaction tube. The tube was sealed and the mixture was heated at C for 1 h Page of 1 Nature Chemical Biology: doi:./nchembio.

11 before being cooled to RT and 1:1 EtOH/Et O (0 ml) was added. Saturated sodium thiosulfate (aq) (0 ml) was added and once the colour had dissipated, the product was isolated by filtration. The resulting precipitate was washed with water ( x 0 ml) and dried under high vacuum at C to give the title compound (.0 g, %) as a pale yellow solid. LCMS (Method A): R T = 0.0 min, m/z =, 1 [M+H] +. 1 H NMR (00 MHz, DMSO d ): δ.0 (br. s, 1H),. (d, J =. Hz, 1H),.0 (s, H). C NMR ( MHz, DMSO d ): δ.,.,.,.,.0,.. Step : tert Butyl (( bromo methyl oxo H pyrazolo[, d]pyrimidin (H) yl)methyl) hydroxypiperidine 1 carboxylate (): A suspension of tert butyl 1 oxa azaspiro[.]octane carboxylate (. g,. mmol), bromo methyl H pyrazolo[, d]pyrimidin (H) one ( g,.1 mmol) and Cs CO (. g,. mmol) in DMF ( ml) was heated at 0 C for 1 h. Upon cooling to RT, the reaction was quenched by the addition of saturated NH Cl (aq) (00 ml) and the mixture was extracted with EtOAc ( x 0 ml). The combined organic phases were passed through a Biotage phase separator, concentrated in vacuo and the residue was purified by flash chromatography (GraceResolv silica 0 g cartridge, 0 0% EtOAc in cyclohexane then 0 % MeOH in EtOAc) to give the title compound (. g, %) as a pale yellow foam. LCMS (Method A): R T = 1.0 min, m/z =, [M+Na] +. 1 H NMR (00 MHz, CDCl ): δ. (s, 1H),.1. (m, H),. (s, H),.. (m, H),..0 (m, H), (m, H), 1. (s, H). Page of 1 Nature Chemical Biology: doi:./nchembio.

12 C NMR ( MHz, CDCl ): δ.,.,.1,.,.,.,., 0.,.,.,.,.,.. Step : Bromo (( hydroxypiperidin yl)methyl) methyl H pyrazolo[, d]pyrimidin (H) one (): A solution of tert butyl (( bromo methyl oxo H pyrazolo[, d]pyrimidin (H) yl)methyl) hydroxypiperidine 1 carboxylate ( g,. mmol) in DCM ( ml) and TFA (. ml) was stirred for min before the reaction mixture was purified using x 0 g SCX cartridges (1:1 DCM/MeOH then 1:1 DCM/ M in NH in MeOH) to give the title compound (. g, %) as a colourless foam. LCMS (Method A): R T = 0. min, m/z =, [M+H] +. 1 H NMR (00 MHz, DMSO d ): δ.0 (s, 1H),. (s, 1H),.0 (s, H),. (s, H),. (dd, J =.1,. Hz, H), 1.1 (dt, J =.,. Hz, H), 1. (dt, J =.0,. Hz, H). C NMR ( MHz, DMSO d ): δ 1.,.,.1,.,.0,.,.1,.1, 0., Step : (R) Bromo (( hydroxy 1 ( phenylbutanoyl)piperidin yl)methyl) methyl H pyrazolo[, d]pyrimidin (H) one (): 1 Page of 1 Nature Chemical Biology: doi:./nchembio.

13 Using a pressure equalized dropping funnel, DIPEA (0. ml, mmol) was added dropwise over min to a solution of bromo (( hydroxypiperidin yl)methyl) methyl H pyrazolo[, d]pyrimidin (H) one (0 g,. mmol), (R) phenylbutanoic acid (. g,. mmol) and HATU (. g,. mmol) in DCM ( ml). After h, the reaction was quenched by the addition of saturated NaHCO (aq) (1 L) and the mixture was extracted with DCM ( x 0 ml). The combined organic phases were passed through a Biotage phase separator, concentrated in vacuo and the residue was purified by flash chromatography (Biotage KP Sil 0 g cartridge, 0 0% EtOAc in cyclohexane then 0 0% MeOH in EtOAc) to give the title compound (. g, %) as colourless solid. LCMS (Method A): R T = 1.0 min, m/z =, 0 [M+H] +. 1 H NMR (00 MHz, DMSO d ): δ.0. (m, 1H),..0 (m, H),.0.0 (m, 1H),.0 (s, H),.0. (m, H),.. (m, 1H),.. (m, H),.1.1 (m, 1H),.. (m, H), (m, H), 1.0 (d, J =.0 Hz, H). C NMR ( MHz, DMSO d ): δ (conformers),. +. (conformers),.0,. +. (conformers),.,.0,.1 +. (conformers),. +. (conformers),. +. (conformers),.,. +. (conformers),., (conformers), 0.,.1,.,.0 +. (conformers),. +. (conformers), (conformers), (conformers). 0 1 Steps and : (R) ( (Aminomethyl)phenyl) (( hydroxy 1 ( phenylbutanoyl)piperidin yl)methyl) methyl H pyrazolo[, d]pyrimidin (H) one (): Page of 1 Nature Chemical Biology: doi:./nchembio.

14 A 1 L round bottom flask was charged with (R) bromo (( hydroxy 1 ( phenylbutanoyl)piperidin yl)methyl) methyl H pyrazolo[, d]pyrimidin (H) one (. g, 1. mmol), SPhos ( mg, 1. mmol), Pd(OAc) ( mg, 0. mmol), ( (((tert butoxycarbonyl)amino)methyl)phenyl)boronic acid (.0 g,. mmol) and K PO (. g,. mmol) and was degassed by evacuating and refilling the flask with N three times using a Schlenk manifold. Under a N atmosphere, n butanol ( ml) was added before the flask was evacuated and refilled with N three times using a Schlenk manifold. The reaction mixture was heated at 0 C for h before being cooled to RT and concentrated in vacuo. The residue was partitioned between water (0 ml) and EtOAc (0 ml). The phases were separated and the aqueous phase was extracted using EtOAc ( x 0 ml). The combined organic phases were dried over Na SO, concentrated in vacuo and the residue was purified by flash chromatography (Biotage KP Sil 0 g cartridge, 0 0% EtOAc in cyclohexane then 0 0% MeOH in EtOAc), the impure fractions were repurified using a GraceResolv silica 0 g cartridge, 0 0% EtOAc in cyclohexane then 0 0% MeOH in EtOAc) to give (R) tert butyl ( (( hydroxy 1 ( phenylbutanoyl)piperidin yl)methyl) methyl oxo, dihydro H pyrazolo[, d]pyrimidin yl)benzylcarbamate (. g, %) as a colourless foam. LCMS (Method A): R T = 1. min, m/z = [M+H] +. A solution of (R) tert butyl ( (( hydroxy 1 Page of 1 Nature Chemical Biology: doi:./nchembio.

15 ( phenylbutanoyl)piperidin yl)methyl) methyl oxo, dihydro Hpyrazolo[, d]pyrimidin yl)benzylcarbamate (. g,. mmol) in DCM ( ml) and TFA ( ml) was stirred for 0 min before the reaction was purified using x g SCX cartridges in parallel (1: MeOH in DCM then 1: M in NH in MeOH in DCM). The basic phases were combined and concentrated to give the crude product (. g). The DCM/MeOH phases were concentrated and the residue was purified using x g SCX cartridges in parallel (1: MeOH in DCM then 1: M in NH in MeOH in DCM) and the basic phases were combined and concentrated to give the crude product (. g). The combined crude products (.1 g) were purified by flash chromatography (GraceResolve silica 0 g cartridge, 0 0% dilute NH in MeOH in DCM) to give the title compound (. g, %) as a colourless solid after freeze drying. LCMS (Method A): R T = 0.1 min (purity >% at nm), m/z = [M+H] +. 1 H NMR (00 MHz, DMSO d ): δ.0. (m, 1H),.. (m, H),.0.1 (m, H),.1. (m, 1H),. (s, 1H),. (s, H),.0. (m, H),.1 (s, H),.0.1 (m, 1H),.. (m, H),.. (m, 1H),.. (m, H),.1 (br. s, H), (m, H), 1.1 (d, J =. Hz, H). C NMR ( MHz, DMSO d ): δ (conformers),. +.1 (conformers),.,.,.,.0,.00,. +.1 (conformers),.0, (conformers),.,.,. +. (conformers),.1,. +.0 (conformers),.,., (conformers), (conformers),.1,.,.0 +. (conformers), (conformers),. +. (conformers), (conformers). HRMS (TOF MS ES+): m/z [M + H] + Calcd for C H N O.1, found.. Page of 1 Nature Chemical Biology: doi:./nchembio.

16 Compound Step 1: (E),, Trifluoro phenylbut enoic acid (1): 1 LiOH ( mg,. mmol) was added to solution of (E) ethyl,, trifluoro phenylbut enoate (J. Fluorine Chem. 0,, ) (1. g, mmol) in THF ( ml) and water ( ml) at RT. After 1 h, the ph of the reaction mixture was adjusted to ph by the addition of 1 M HCl (aq) and the mixture was extracted with DCM ( x ml) using a Biotage phase separator. The combined organic phases were concentrated and the product was dried in vacuo to give (E),, trifluoro phenylbut enoic acid (1.0 g, %) as a colourless solid. LCMS (Method A): R T = 1. min, m/z = [M H]. 1 H NMR (00 MHz, DMSO d ): δ.1 (s, 1H),.. (m, H),.1 (dd, J =.,. Hz, H),. (q, J = 1. Hz, 1H). 1 F NMR ( MHz, DMSO d ): δ.. C NMR (1 MHz, DMSO d ): δ 1.,. (q, J = 0.0 Hz), 0.0,.,.,.1,. (q, J =. Hz),. (q, J =. Hz). 1 1 Step : (R),, Trifluoro phenylbutanoic acid (1): Page 1 of 1 Nature Chemical Biology: doi:./nchembio.

17 A suspension of bis(norbornadiene)rhodium(i) tetrafluoroborate (0. mg, 1. μmol) and Walphos SL W00 ( mg, 1. μmol) in MeOH (0 ml) in a 00 ml glass reactor autoclave was degassed with N. After 0 min, a solution was obtained and (E),, trifluoro phenylbut enoic acid (00 mg,.1 mmol) was added. The reaction was stirred under. bar H for h before being concentrated in vacuo to give the title compound (1 g, >0%) as a colourless solid. This material was used without further purification. LCMS (Method A): R T = 1. min, m/z = 1 [M H]. 1 H NMR (00 MHz, CDCl ): δ.0. (m, H),. (pd, J =.,. Hz, 1H),.0 (dd, J = 1.,. Hz, 1H),. (dd, J = 1.,. Hz, 1H). Spectral data matches that reported in the literature. A M TMS diazomethane solution in hexanes (0.0 ml, 0.0 mmol) was added to a solution of (R),, trifluoro phenylbutanoic acid ( mg, 0.0 mmol) in MeOH (0 µl) and toluene (0. ml). After 1 hour, the reaction mixture was purified directly by chromatography ( x 0. cm silica plug, 0 0% Et O in pentane) to give (R) methyl,, trifluoro phenylbutanoate ( mg, %) as a pale yellow oil. The Et O/pentane were removed carefully to avoid loss of material. The ee was measured using a Diacel OJ H column (0 x. mm, micron) and 1% iproh in hexane as the mobile phase. The racemic sample gave peaks: R T =.0 min (.01%) and R T =. min (0.0%). This sample gave the same peaks: R T =.01 min (0.%) and R T =.0 min (.%). This corresponds to an ee measurement for the acid that is >%. The acid was assigned as R by comparison Page 1 of 1 Nature Chemical Biology: doi:./nchembio.

18 with literature in which the authors use the same OJ stationary phase under which conditions the (R) enantiomer has the longer retention time. Step : (R) Bromo (( hydroxy 1 (,, trifluoro phenylbutanoyl)piperidin yl)methyl) methyl H pyrazolo[, d]pyrimidin (H) one (1): DIPEA (0. ml, 1. mmol) was added to a suspension of bromo (( hydroxypiperidin yl)methyl) methyl H pyrazolo[, d]pyrimidin (H) one ( mg, 0. mmol), (R),, trifluoro phenylbutanoic acid (0 mg, 0. mmol) and HATU ( mg, 0. mmol) in DCM (0 ml). After 1 h, the reaction was quenched by the addition of saturated NaHCO (aq) (0 ml) and the mixture was extracted with DCM ( x 0 ml) using a Biotage phase separator. The combined organic phases were concentrated in vacuo and the residue was purified by flash chromatography (Biotage KP NH g cartridge, 0 0% EtOAc in cyclohexane then 0 0% MeOH in EtOAc) to give the title compound ( mg, %) as a colourless solid. LCMS (Method B): R T = 1.1 min, m/z, [M+H] +. 1 H NMR (00 MHz, DMSO d ): δ.0. (m, 1H),..0 (m, H),. (s, 1H),..0 (m, 1H),.0 (s, H),.00. (m, H),.0.1 (m, 1H),.. (m, H),.00. (m, H), (m, H). C NMR ( MHz, DMSO d ): δ (conformers),. +. (conformers), (conformers),., (conformers),.1.0 (m, due to conformers and coupling with CF ),.1,. +. (conformers),.0 +. (conformers),.,. + Page 1 of 1 Nature Chemical Biology: doi:./nchembio.

19 . (conformers),. +.0 (conformers),.. (m, due to conformers and coupling with CF ), 0.,. +. (conformers),. +. (conformers),.0 +. (conformers), 1.. Signal for NCH is under DMSO and the CF is not observed. Steps and : (R) ( (Aminomethyl)phenyl) (( hydroxy 1 (,, trifluoro phenylbutanoyl)piperidin yl)methyl) methyl H pyrazolo[, d]pyrimidin (H) one (): A mixture of (R) bromo (( hydroxy 1 (,, trifluoro phenylbutanoyl)piperidin yl)methyl) methyl H pyrazolo[, d]pyrimidin (H) one (0 mg, 0.1 mmol), ( (((tert butoxycarbonyl)amino)methyl)phenyl)boronic acid (1 mg, 0. mmol), Pd(PPh ) ( mg, 0.0 mmol), K PO (1 mg, 1. mmol), 1, dioxane ( ml) and water (1 ml) in a reaction tube was degassed by bubbling N for 0 min. The reaction tube was sealed and the reaction was heated at 0 C under microwave irradiation for 0 min. The reaction mixture was diluted with saturated NH Cl (aq) (0 ml) and extracted with DCM ( x 0 ml) using a Biotage phase separator. The combined organic phases were concentrated in vacuo and the residue was purified by flash chromatography (0 g GraceResolv silica, 0 0% EtOAc in cyclohexane then 0 % MeOH in EtOAc) to give (R) tert butyl ( (( hydroxy 1 Page 1 of 1 Nature Chemical Biology: doi:./nchembio.

20 (,, trifluoro phenylbutanoyl)piperidin yl)methyl) methyl oxo, dihydro H pyrazolo[, d]pyrimidin yl)benzylcarbamate (00 mg, %) as a pale yellow solid. LCMS (Method A): R T = 1. min, m/z [M+H] +. A solution of (R) tert butyl ( (( hydroxy 1 (,, trifluoro phenylbutanoyl)piperidin yl)methyl) methyl oxo, dihydro H pyrazolo[, d]pyrimidin yl)benzylcarbamate (00 mg, 0.00 mmol) in DCM ( ml) and TFA (1 ml) was stirred at RT for min. The reaction mixture was purified using a g SCX cartridge (MeOH then M in NH in MeOH). The basic phases were combined, concentrated in vacuo and the residue was purified by flash chromatography (GraceResolv silica g cartridge, 0 0%, EtOAc in cyclohexane then 0 % MeOH in EtOAc; then Biotage KP NH g cartridge, 0 0%, EtOAc in cyclohexane then 0 % MeOH in EtOAc) to give the title compound (0 mg, %) as a colourless solid after lyophilization. LCMS (Method B): R T = 0.1 min (purity >% at nm), m/z [M+H] +. 1 H NMR (00 MHz, DMSO d ): δ.0. (m, 1H),.0.0 (m, H),.. (m, H),.. (m, H),.. (m, H),. (s, 1H),..0 (m, 1H),. (s, H),.0. (m, H),.1 (s, H),.0.1 (m, 1H),.. (m, H),.0.0 (m, H),. (s, H), 1.1 (td, J =.,.1,. Hz, 0.H), (m,.h), (m, 1H). C NMR ( MHz, DMSO d ): δ (conformers),. +.1 (conformers),. +. (conformers),.,.0,.. (m, due to conformers and coupling with CF ),.1,.1,.,.,.,.,.0,.,.,.,.0,.0,., (conformers),. +. (conformers),..0 (m, due to conformers and coupling with CF ),., 0.,.,. +. (conformers),. +.0 (conformers), (conformers), 1.. Page 0 of 1 Nature Chemical Biology: doi:./nchembio.

21 The signals between 0 ppm are complex due to the conformers and the CF signals. HRMS (TOF MS ES+): m/z [M + H] + Calcd for C H N O F., found.0. Compound (ent ) Compound ent was made by an identical method as starting from Bromo (( hydroxypiperidin yl)methyl) methyl H pyrazolo[, d]pyrimidin (H) one but using (S) phenylbutanoic acid in the coupling step. References 1 Bae, I. H. et al. PCT Int. Appl. (0), WO 00. Oslob, J. D. et al. PCT Int. Appl. (00), WO 000. Dong K. et al. Angew. Chem. Int. Ed. 0,, Page 1 of 1 Nature Chemical Biology: doi:./nchembio.

Identification and Structure-Guided Development of Pyrimidinone Based USP7 Inhibitors

Identification and Structure-Guided Development of Pyrimidinone Based USP7 Inhibitors SUPPORTING INFORMATION Identification and Structure-Guided Development of Pyrimidinone Based USP7 Inhibitors Colin R. O Dowd *, Matthew D. Helm, J. S. Shane Rountree, Jakub T. Flasz, Elias Arkoudis, Hugues

More information

p-toluenesulfonic Acid-Mediated 1,3-Dipolar Cycloaddition of

p-toluenesulfonic Acid-Mediated 1,3-Dipolar Cycloaddition of Supporting Information for: p-toluenesulfonic Acid-Mediated 1,3-Dipolar Cycloaddition of Nitroolefins with NaN 3 for Synthesis of 4-Aryl-NH-1,2,3-triazoles Xue-Jing Quan, Zhi-Hui Ren, Yao-Yu Wang, and

More information

Direct Aerobic Carbonylation of C(sp 2 )-H and C(sp 3 )-H Bonds through Ni/Cu Synergistic Catalysis with DMF as the Carbonyl Source

Direct Aerobic Carbonylation of C(sp 2 )-H and C(sp 3 )-H Bonds through Ni/Cu Synergistic Catalysis with DMF as the Carbonyl Source Direct Aerobic Carbonylation of C(sp 2 )-H and C(sp 3 )-H Bonds through Ni/Cu Synergistic Catalysis with DMF as the Carbonyl Source Xuesong Wu, Yan Zhao, and Haibo Ge* Table of Contents General Information...

More information

mm C3a. 1 mm C3a Time (s) C5a. C3a. Blank. 10 mm Time (s) Time (s)

mm C3a. 1 mm C3a Time (s) C5a. C3a. Blank. 10 mm Time (s) Time (s) 125 I-C5a (cpm) Fluorescnece Em 520nm a 4000 3000 2000 1000 c 0 5000 4000 3000 2000 Blank C5a C3a 6 0.3 mm C3a 7 9 10 11 12 13 15 16 0.3 mm C5a 0 300 600 900 1200 Time (s) 17 Fluorescnece Em 520nm Fluorescnece

More information

Supporting Information. Recyclable hypervalent-iodine-mediated solid-phase peptide

Supporting Information. Recyclable hypervalent-iodine-mediated solid-phase peptide Supporting Information Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis Dan Liu, Ya-Li Guo, Jin Qu and Chi Zhang* for Address: State Key Laboratory of Elemento-Organic

More information

Lewis acid-catalyzed regioselective synthesis of chiral α-fluoroalkyl amines via asymmetric addition of silyl dienolates to fluorinated sulfinylimines

Lewis acid-catalyzed regioselective synthesis of chiral α-fluoroalkyl amines via asymmetric addition of silyl dienolates to fluorinated sulfinylimines Supporting Information for Lewis acid-catalyzed regioselective synthesis of chiral α-fluoroalkyl amines via asymmetric addition of silyl dienolates to fluorinated sulfinylimines Yingle Liu a, Jiawang Liu

More information

Stereoselective Aza-Darzens Reactions of Tert- Butanesulfinimines: Convenient Access to Chiral Aziridines

Stereoselective Aza-Darzens Reactions of Tert- Butanesulfinimines: Convenient Access to Chiral Aziridines Stereoselective Aza-Darzens Reactions of Tert- Butanesulfinimines: Convenient Access to Chiral Aziridines Toni Moragas Solá, a Ian Churcher, b William Lewis a and Robert A. Stockman* a Supplementary Information

More information

Supporting Information. Radical fluorination powered expedient synthesis of 3 fluorobicyclo[1.1.1]pentan 1 amine

Supporting Information. Radical fluorination powered expedient synthesis of 3 fluorobicyclo[1.1.1]pentan 1 amine Electronic Supplementary Material (ESI) for rganic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2015 Supporting Information Radical fluorination powered expedient synthesis

More information

Supporting Information. Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2007

Supporting Information. Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2007 Supporting Information Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2007 Supporting Information General. NMR spectra for identification of intermediates and final compoundswere recorded

More information

An Unusual Glycosylation Product from a Partially Protected Fucosyl Donor. under Silver Triflate activation conditions. Supporting information

An Unusual Glycosylation Product from a Partially Protected Fucosyl Donor. under Silver Triflate activation conditions. Supporting information An Unusual Glycosylation Product from a Partially Protected Fucosyl Donor under Silver Triflate activation conditions Robin Daly a and Eoin M. Scanlan* a e-mail: eoin.scanlan@tcd.ie a Trinity Biomedical

More information

Masatoshi Shibuya,Takahisa Sato, Masaki Tomizawa, and Yoshiharu Iwabuchi* Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences,

Masatoshi Shibuya,Takahisa Sato, Masaki Tomizawa, and Yoshiharu Iwabuchi* Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Oxoammonium ion/naclo 2 : An Expedient, Catalytic System for One-pot Oxidation of Primary Alcohols to Carboxylic Acid with Broad Substrate Applicability Masatoshi Shibuya,Takahisa Sato, Masaki Tomizawa,

More information

Supporting Information

Supporting Information Supporting Information Unconventional Passerini Reaction towards α-aminoxyamides Ajay L. Chandgude, Alexander Dömling* Department of Drug Design, University of Groningen, Antonius Deusinglaan 1, 9713 AV

More information

Supporting Information Synthesis of 2-Aminobenzonitriles through Nitrosation Reaction and Sequential Iron(III)-Catalyzed C C Bond Cleavage of 2-Arylin

Supporting Information Synthesis of 2-Aminobenzonitriles through Nitrosation Reaction and Sequential Iron(III)-Catalyzed C C Bond Cleavage of 2-Arylin Supporting Information Synthesis of 2-Aminobenzonitriles through Nitrosation Reaction and Sequential Iron(III)-Catalyzed C C Bond Cleavage of 2-Arylindoles Wei-Li Chen, Si-Yi Wu, Xue-Ling Mo, Liu-Xu Wei,

More information

Nitro-Grela-type complexes containing iodides. robust and selective catalysts for olefin metathesis

Nitro-Grela-type complexes containing iodides. robust and selective catalysts for olefin metathesis Supporting Information for Nitro-Grela-type complexes containing iodides robust and selective catalysts for olefin metathesis under challenging conditions. Andrzej Tracz, 1,2 Mateusz Matczak, 1 Katarzyna

More information

Regioective Halogenation of 2-Substituted-1,2,3-Triazole via sp 2 C-H Activation

Regioective Halogenation of 2-Substituted-1,2,3-Triazole via sp 2 C-H Activation Regioective Halogenation of 2-Substituted-1,2,3-Triazole via sp 2 C-H Activation Qingshan Tian, Xianmin Chen, Wei Liu, Zechao Wang, Suping Shi, Chunxiang Kuang,* Department of Chemistry, Tongji University,

More information

Supporting Information. for. Synthesis of dye/fluorescent functionalized. dendrons based on cyclotriphosphazene

Supporting Information. for. Synthesis of dye/fluorescent functionalized. dendrons based on cyclotriphosphazene Supporting Information for Synthesis of dye/fluorescent functionalized dendrons based on cyclotriphosphazene Aurélien Hameau 1,2, Sabine Fuchs 1,2, Régis Laurent 1,2, Jean-Pierre Majoral* 1,2 and Anne-Marie

More information

Supporting Information

Supporting Information Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2018 Supporting Information Facile Three-Step Synthesis and Photophysical Properties of [8]-, [9]-,

More information

Direct ortho-c H Functionalization of Aromatic Alcohols Masked by Acetone Oxime Ether via exo-palladacycle

Direct ortho-c H Functionalization of Aromatic Alcohols Masked by Acetone Oxime Ether via exo-palladacycle Direct ortho-c H Functionalization of Aromatic Alcohols Masked by Acetone Oxime Ether via exo-palladacycle Kun Guo, Xiaolan Chen, Mingyu Guan, and Yingsheng Zhao* Key Laboratory of Organic Synthesis of

More information

Supporting information

Supporting information Supporting information Diversity Oriented Asymmetric Catalysis (DOAC): Stereochemically Divergent Synthesis of Thiochromanes Using an Imidazoline-aminophenol aminophenol (IAP)-Ni Catalyzed Michael/Henry

More information

Electronic Supplementary Information

Electronic Supplementary Information Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2015 Electronic Supplementary Information ovel pseudo[2]rotaxanes constructed by selfassembly of dibenzyl

More information

Solid Phase Peptide Synthesis (SPPS) and Solid Phase. Fragment Coupling (SPFC) Mediated by Isonitriles

Solid Phase Peptide Synthesis (SPPS) and Solid Phase. Fragment Coupling (SPFC) Mediated by Isonitriles Solid Phase Peptide Synthesis (SPPS) and Solid Phase Fragment Coupling (SPFC) Mediated by Isonitriles Ting Wang a and Samuel J. Danishefsky a,b,* alaboratory for Bioorganic Chemistry, Sloan- Kettering

More information

Supporting Information. Efficient copper-catalyzed Michael addition of acrylic derivatives with primary alcohols in the presence of base

Supporting Information. Efficient copper-catalyzed Michael addition of acrylic derivatives with primary alcohols in the presence of base Supporting Information Efficient copper-catalyzed Michael addition of acrylic derivatives with primary alcohols in the presence of base Feng Wang, a Haijun Yang, b Hua Fu, b,c * and Zhichao Pei a * a College

More information

Supplemental Material

Supplemental Material Supplemental Material General Methods Unless otherwise indicated, all anhydrous solvents were commercially obtained and stored under nitrogen. Reactions were performed under an atmosphere of dry nitrogen

More information

ph Switchable and Fluorescent Ratiometric Squarylium Indocyanine Dyes as Extremely Alkaline Sensors

ph Switchable and Fluorescent Ratiometric Squarylium Indocyanine Dyes as Extremely Alkaline Sensors ph Switchable and Fluorescent Ratiometric Squarylium Indocyanine Dyes as Extremely Alkaline Sensors Jie Li, Chendong Ji, Wantai Yang, Meizhen Yin* State Key Laboratory of Chemical Resource Engineering,

More information

Supplementary Materials Contents

Supplementary Materials Contents Supplementary Materials Contents Supporting information... S1 1. General Information & Materials... S2 2. General Procedure for ptimization of Amidation of Aryl Bromides with Copper/,-Dimethylglycine Catalytic

More information

Supporting Information. for. Access to pyrrolo-pyridines by gold-catalyzed. hydroarylation of pyrroles tethered to terminal alkynes

Supporting Information. for. Access to pyrrolo-pyridines by gold-catalyzed. hydroarylation of pyrroles tethered to terminal alkynes Supporting Information for Access to pyrrolo-pyridines by gold-catalyzed hydroarylation of pyrroles tethered to terminal alkynes Elena Borsini 1, Gianluigi Broggini* 1, Andrea Fasana 1, Chiara Baldassarri

More information

Ethyl 2-hydroxy-4-methyl-1-((prop-2-yn-1-yloxy)methyl)cyclohex-3-enecarboxylate (16):

Ethyl 2-hydroxy-4-methyl-1-((prop-2-yn-1-yloxy)methyl)cyclohex-3-enecarboxylate (16): General methods: 1 H NMR and 13 C NMR spectra were recorded in CDCl 3 or CDCl3 and CCl 4 as solvent on 300 MHz or 500 MHz spectrometer at ambient temperature. The coupling constant J is given in Hz. The

More information

Supporting Information

Supporting Information Investigation of self-immolative linkers in the design of hydrogen peroxide metalloprotein inhibitors Jody L. Major Jourden, Kevin B. Daniel, and Seth M. Cohen* Department of Chemistry and Biochemistry,

More information

Supporting Information. Design and Synthesis of Bicyclic Pyrimidinones as Potent and Orally. Bioavailable HIV-1 Integrase Inhibitors.

Supporting Information. Design and Synthesis of Bicyclic Pyrimidinones as Potent and Orally. Bioavailable HIV-1 Integrase Inhibitors. Supporting Information Design and Synthesis of Bicyclic Pyrimidinones as Potent and Orally Bioavailable HIV-1 Integrase Inhibitors. Ester Muraglia, * Olaf Kinzel, Cristina Gardelli, Benedetta Crescenzi,

More information

Preparation of Fluorinated Tetrahydropyrans and Piperidines using a New Nucleophilic Fluorination Reagent DMPU/HF

Preparation of Fluorinated Tetrahydropyrans and Piperidines using a New Nucleophilic Fluorination Reagent DMPU/HF Supporting information Preparation of Fluorinated Tetrahydropyrans and Piperidines using a New Nucleophilic Fluorination Reagent DMPU/HF Otome E. Okoromoba, a Gerald B. Hammond, a, * Bo Xu b, * a Department

More information

Supporting Information. for. Pd-catalyzed decarboxylative Heck vinylation of. 2-nitro-benzoates in the presence of CuF 2

Supporting Information. for. Pd-catalyzed decarboxylative Heck vinylation of. 2-nitro-benzoates in the presence of CuF 2 Supporting Information for Pd-catalyzed decarboxylative Heck vinylation of 2-nitro-benzoates in the presence of CuF 2 Lukas J. Gooßen*, Bettina Zimmermann, Thomas Knauber Address: Department of Chemistry,

More information

Preparation of Stable Aziridinium Ions and Their Ring Openings

Preparation of Stable Aziridinium Ions and Their Ring Openings Supplementary Information Preparation of Stable Aziridinium Ions and Their Ring Openings Yongeun Kim a Hyun-Joon Ha*, a Sae Young Yun b and Won Koo Lee,*,b a Department of Chemistry and Protein Research

More information

Cu-Catalyzed Direct C6-Arylation of Indoles

Cu-Catalyzed Direct C6-Arylation of Indoles Cu-Catalyzed Direct C6-Arylation of Indoles (Supporting Information) Youqing Yang, Ruirui Li, Yue Zhao, Dongbing Zhao, and Zhuangzhi Shi*, State Key Laboratory of Coordination Chemistry, Collaborative

More information

Pyridazine N-Oxides as Precursors of Metallocarbenes: Rhodium-Catalyzed Transannulation with Pyrroles. Supporting Information

Pyridazine N-Oxides as Precursors of Metallocarbenes: Rhodium-Catalyzed Transannulation with Pyrroles. Supporting Information Pyridazine N-Oxides as Precursors of Metallocarbenes: Rhodium-Catalyzed Transannulation with Pyrroles Vinaykumar Kanchupalli, Desna Joseph and Sreenivas Katukojvala* Department of Chemistry, Indian Institute

More information

Enantioselective synthesis of anti- and syn-β-hydroxy-α-phenyl carboxylates via boron-mediated asymmetric aldol reaction

Enantioselective synthesis of anti- and syn-β-hydroxy-α-phenyl carboxylates via boron-mediated asymmetric aldol reaction Enantioselective synthesis of anti- and syn-β-hydroxy-α-phenyl carboxylates via boron-mediated asymmetric aldol reaction P. Veeraraghavan Ramachandran* and Prem B. Chanda Department of Chemistry, Purdue

More information

Supporting Information

Supporting Information Supporting Information for Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5- tetrafluorocyclohexane Mohammed Salah Ayoup 1,2, David B. Cordes 1,

More information

Palladium-catalyzed Decarbonylative Alkynylation of Aromatic Esters

Palladium-catalyzed Decarbonylative Alkynylation of Aromatic Esters Palladium-catalyzed Decarbonylative Alkynylation of Aromatic Esters Toshimasa Okita, 1 Kazushi Kumazawa, 2 Ryosuke Takise, 2 Kei Muto, 1 Kenichiro Itami,* 2,3 and Junichiro Yamaguchi* 1 1 Department of

More information

Manganese powder promoted highly efficient and selective synthesis of fullerene mono- and biscycloadducts at room temperature

Manganese powder promoted highly efficient and selective synthesis of fullerene mono- and biscycloadducts at room temperature Supplementary Information Manganese powder promoted highly efficient and selective synthesis of fullerene mono- and biscycloadducts at room temperature Weili Si 1, Xuan Zhang 1, Shirong Lu 1, Takeshi Yasuda

More information

Allenylphosphine oxides as simple scaffolds for. phosphinoylindoles and phosphinoylisocoumarins

Allenylphosphine oxides as simple scaffolds for. phosphinoylindoles and phosphinoylisocoumarins Supporting Information for Allenylphosphine oxides as simple scaffolds for phosphinoylindoles and phosphinoylisocoumarins G. Gangadhararao, Ramesh Kotikalapudi, M. Nagarjuna Reddy and K. C. Kumara Swamy*

More information

Supporting Information

Supporting Information Supporting Information Direct Synthesis of Benzimidazoles by Dehydrogenative Coupling of Aromatic Diamines and Alcohols Catalyzed by Cobalt Prosenjit Daw, Yehoshoa Ben-David, and David Milstein* Department

More information

Supporting Information for. Use of the Curtius Rearrangement of Acryloyl Azides in the Synthesis of. 3,5-Disubstituted Pyridines: Mechanistic Studies

Supporting Information for. Use of the Curtius Rearrangement of Acryloyl Azides in the Synthesis of. 3,5-Disubstituted Pyridines: Mechanistic Studies Supporting Information for Use of the Curtius Rearrangement of Acryloyl Azides in the Synthesis of 3,5-Disubstituted Pyridines: Mechanistic Studies Ta-Hsien Chuang* a, Yu-Chi Chen b and Someshwar Pola

More information

Supporting Information. Nitrodibenzofuran: a One- and Two-Photon Sensitive Protecting Group that is Superior to

Supporting Information. Nitrodibenzofuran: a One- and Two-Photon Sensitive Protecting Group that is Superior to Supporting Information Nitrodibenzofuran: a One- and Two-Photon Sensitive Protecting Group that is Superior to Brominated Hydroxycoumarin for Thiol Caging in Peptides M. Mohsen Mahmoodi, Daniel Abate-Pella,

More information

Triptycene-Based Small Molecules Modulate (CAG) (CTG) Repeat Junctions

Triptycene-Based Small Molecules Modulate (CAG) (CTG) Repeat Junctions Electronic Supplementary Material (ESI) for Chemical Science. This journal is The Royal Society of Chemistry 2015 Triptycene-Based Small Molecules Modulate (CAG) (CTG) Repeat Junctions Stephanie A. Barros

More information

Supporting Information for. Boronic Acid Functionalized Aza-Bodipy (azabdpba) based Fluorescence Optodes for the. analysis of Glucose in Whole Blood

Supporting Information for. Boronic Acid Functionalized Aza-Bodipy (azabdpba) based Fluorescence Optodes for the. analysis of Glucose in Whole Blood Supporting Information for Boronic Acid Functionalized Aza-Bodipy (azabdpba) based Fluorescence Optodes for the analysis of Glucose in Whole Blood Yueling Liu, Jingwei Zhu, Yanmei Xu, Yu Qin*, Dechen Jiang*

More information

Supporting Information

Supporting Information Supporting Information Wiley-VCH 2008 69451 Weinheim, Germany Enantioselective Rhodium-catalyzed Addition of Arylboronic Acids to α-ketoesters Hai-Feng Duan, Jian-Hua Xie, Xiang-Chen Qiao, Li-Xin Wang,

More information

Structure Enabled Design of BAZ2-ICR, a Chemical Probe Targeting the Bromodomains of BAZ2A and BAZ2B. Table of Contents

Structure Enabled Design of BAZ2-ICR, a Chemical Probe Targeting the Bromodomains of BAZ2A and BAZ2B. Table of Contents Supporting information For Structure Enabled Design of BAZ2-ICR, a Chemical Probe Targeting the Bromodomains of BAZ2A and BAZ2B Ludovic Drouin, # Sally McGrath, # Lewis R. Vidler, # Apirat Chaikuad, Octavio

More information

Efficient Metal-Free Pathway to Vinyl Thioesters with Calcium Carbide as the Acetylene Source

Efficient Metal-Free Pathway to Vinyl Thioesters with Calcium Carbide as the Acetylene Source Electronic Supplementary Material (ESI) for Green Chemistry. This journal is The Royal Society of Chemistry 2015 Supporting Information Efficient Metal-Free Pathway to Vinyl Thioesters with Calcium Carbide

More information

Supporting Materials. Experimental Section. internal standard TMS (0 ppm). The peak patterns are indicated as follows: s, singlet; d,

Supporting Materials. Experimental Section. internal standard TMS (0 ppm). The peak patterns are indicated as follows: s, singlet; d, CuBr-Catalyzed Efficient Alkynylation of sp 3 C-H Bonds Adjacent to a itrogen Atom Zhiping Li and Chao-Jun Li* Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, Quebec H3A

More information

Supporting Information

Supporting Information Electronic Supplementary Material (ESI) for rganic Chemistry Frontiers. This journal is the Partner rganisations 2016 Supporting Information Fangyi Li, Changgui Zhao, and Jian Wang* Department of Pharmacology

More information

Analysis of fatty acid metabolism using Click-Chemistry and HPLC-MS

Analysis of fatty acid metabolism using Click-Chemistry and HPLC-MS Analysis of fatty acid metabolism using Click-Chemistry and HPLC-MS Alexander J. Pérez and Helge B. Bode -Supporting Information- Contents Experimental section Supplementary figures NMR spectra Page S2

More information

Electronic Supplementary Material

Electronic Supplementary Material Electronic Supplementary Material PAMAM Dendrimers Bearing Electron-Donating Chromophores: Fluorescence and Electrochemical Properties Bing-BingWang a, Xin Zhang a, Ling Yang a, Xin-Ru Jia* a, Yan Ji a,

More information

CDI Mediated Monoacylation of Symmetrical Diamines and Selective Acylation of Primary Amines of Unsymmetrical Diamines

CDI Mediated Monoacylation of Symmetrical Diamines and Selective Acylation of Primary Amines of Unsymmetrical Diamines Supporting information: CDI Mediated Monoacylation of Symmetrical Diamines and Selective Acylation of Primary Amines of Unsymmetrical Diamines Sanjeev K. Verma*, Ramarao Ghorpade, Ajay Pratap and M. P.

More information

Iodide as an Activating Agent for Acid Chlorides in Acylation Reactions.

Iodide as an Activating Agent for Acid Chlorides in Acylation Reactions. Iodide as an Activating Agent for Acid Chlorides in Acylation Reactions. Russell J. Wakeham a, James E. Taylor a, Steven D. Bull a, James A. Morris b and Jonathan M. J. Williams a a Department of Chemistry,

More information

Supporting Information

Supporting Information Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2011 Supporting Information Potassium tert-butoxide Mediated Heck-Type Cyclization/Isomerization

More information

Preparation, isolation and characterization of N α -Fmoc-peptide isocyanates: Solution synthesis of oligo-α-peptidyl ureas

Preparation, isolation and characterization of N α -Fmoc-peptide isocyanates: Solution synthesis of oligo-α-peptidyl ureas SUPPORTING INFORMATION Preparation, isolation and characterization of N α -Fmoc-peptide isocyanates: Solution synthesis of oligo-α-peptidyl ureas Vommina V. Suresh Babu*, Basanagoud S. Patil, and Rao Venkataramanarao

More information

Zinc Chloride Promoted Formal Oxidative Coupling of Aromatic Aldehydes and Isocyanides to α- Ketoamides

Zinc Chloride Promoted Formal Oxidative Coupling of Aromatic Aldehydes and Isocyanides to α- Ketoamides Supporting information for Zinc Chloride Promoted Formal xidative Coupling of Aromatic Aldehydes and Isocyanides to α- Ketoamides Marinus Bouma, Géraldine Masson* and Jieping Zhu* Institut de Chimie des

More information

Facile Cu(II) mediated conjugation of thioesters and thioacids to peptides and proteins under mild conditions

Facile Cu(II) mediated conjugation of thioesters and thioacids to peptides and proteins under mild conditions Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2018 Facile Cu(II) mediated conjugation of thioesters and thioacids to peptides

More information

Orvinols with Mixed Kappa/Mu Opioid Receptor Agonist Activity

Orvinols with Mixed Kappa/Mu Opioid Receptor Agonist Activity Supporting Information Orvinols with Mixed Kappa/Mu Opioid Receptor Agonist Activity Greedy, Benjamin M.; Bradbury, Faye.; Thomas, Mark P.; Grivas, Konstantinos; Cami-Kobeci, Gerta; Archambeau, Ashley.;

More information

Copyright Wiley-VCH Verlag GmbH, D Weinheim, Angew. Chem

Copyright Wiley-VCH Verlag GmbH, D Weinheim, Angew. Chem Copyright Wiley-VCH Verlag GmbH, D-69451 Weinheim, 2000. Angew. Chem. 2000. Supporting Information for Salen as Chiral Activator : Anti vs Syn Switchable Diastereoselection in the Enantioselective Addition

More information

Supporting Information

Supporting Information Supporting Information Wiley-VCH 2008 69451 Weinheim, Germany Supporting Information Enantioselective Cu-catalyzed 1,4-Addition of Various Grignard Reagents to Cyclohexenone using Taddol-derived Phosphine-Phosphite

More information

Supporting Information

Supporting Information Supporting Information De Novo Synthesis of Polysubstituted Naphthols and Furans Using Photoredox Neutral Coupling of Alkynes with 2-Bromo-1,3-Dicarbonyl Compounds Heng Jiang, Yuanzheng Cheng, Yan Zhang,*

More information

SUPPORTING INFORMATION FOR. Regioselective Ring-opening and Isomerization Reactions of 3,4-Epoxyesters Catalyzed by Boron Trifluoride

SUPPORTING INFORMATION FOR. Regioselective Ring-opening and Isomerization Reactions of 3,4-Epoxyesters Catalyzed by Boron Trifluoride S1 SUPPORTING INFORMATION FOR Regioselective Ring-opening and Isomerization Reactions of 3,4-Epoxyesters Catalyzed by Boron Trifluoride Javier Izquierdo, Santiago Rodríguez and Florenci V. González* Departament

More information

Supporting Information

Supporting Information Supporting Information Asymmetric Catalysis of the Carbonyl-Amine Condensation: Kinetic Resolution of Primary Amines Sayantani Das, Nilanjana Majumdar, Chandra Kanta De, Dipti Sankar Kundu, Arno Döhring,

More information

A Facile Route to Triazolopyrimidines Using Continuous Flow Chemistry. Table of Contents

A Facile Route to Triazolopyrimidines Using Continuous Flow Chemistry. Table of Contents Supporting Information 1 A Facile Route to Triazolopyrimidines Using Continuous Flow Chemistry Sara Sadler a, Meaghan M. Sebeika a, Nicholas L. Kern a, David E. Bell a, Chloe A. Laverack a, Devan J. Wilkins

More information

SUPPORTING INFORMATION. Transition metal-promoted synthesis of 2-aryl/heteroaryl-thioquinazoline: C-S

SUPPORTING INFORMATION. Transition metal-promoted synthesis of 2-aryl/heteroaryl-thioquinazoline: C-S 1 SUPPORTING INFORMATION Transition metal-promoted synthesis of 2-aryl/heteroaryl-thioquinazoline: C-S Bond formation by Chan-Lam Cross-Coupling Reaction SATYA KARUNA PULAKHANDAM a, NARESH KUMAR KATARI

More information

Supporting Information

Supporting Information Supporting Information B(C 6 F 5 ) 3 -catalyzed Regioselective Deuteration of Electronrich Aromatic and Heteroaromatic compounds Wu Li, Ming-Ming Wang, Yuya Hu and Thomas Werner* Leibniz-Institute of Catalysis

More information

Schwartz s reagent-mediated regiospecific synthesis of 2,3-disubstituted indoles from isatins

Schwartz s reagent-mediated regiospecific synthesis of 2,3-disubstituted indoles from isatins Electronic Supplementary Information (ESI) Schwartz s reagent-mediated regiospecific synthesis of 2,3-disubstituted indoles from isatins A. Ulikowski and B. Furman* Institute of Organic Chemistry, Polish

More information

SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION doi:10.1038/nature19056 Metallaphotoredox-Catalyzed sp 3 sp 3 Cross- Coupling of Carboxylic Acids with Alkyl Halides Craig P. Johnston, Russell T. Smith, Simon Allmendinger, and David W. C. MacMillan WWW.NATURE.COM/NATURE

More information

Supporting Information. Palladium-Catalyzed Formylation of Aryl Iodides with HCOOH as

Supporting Information. Palladium-Catalyzed Formylation of Aryl Iodides with HCOOH as Supporting Information Palladium-Catalyzed Formylation of Aryl Iodides with HCOOH as CO Source Guanglong Sun,,, Xue Lv,,, Yinan Zhang, Min Lei,*,, and Lihong Hu*, Jiangsu Key Laboratory for Functional

More information

Ynamides as racemization-free coupling reagents for amide and peptide synthesis

Ynamides as racemization-free coupling reagents for amide and peptide synthesis Ynamides as racemization-free coupling reagents for amide and peptide synthesis Long Hu, Silin Xu, Zhenguang Zhao, Yang Yang, Zhiyuan Peng, Ming Yang, Changliu Wang, Junfeng Zhao* Key Laboratory of Chemical

More information

Asymmetric organocatalytic diboration of alkenes

Asymmetric organocatalytic diboration of alkenes Asymmetric organocatalytic diboration of alkenes Amadeu Bonet, a Cristina Solé, Henrik Gulyás,* Elena Fernández* a Dept. Química Física i Inorgànica, University Rovira i Virgili, C/Marcel lí Domingo s/n,

More information

Fluorescent probes for detecting monoamine oxidase activity and cell imaging

Fluorescent probes for detecting monoamine oxidase activity and cell imaging Fluorescent probes for detecting monoamine oxidase activity and cell imaging Xuefeng Li, Huatang Zhang, Yusheng Xie, Yi Hu, Hongyan Sun *, Qing Zhu * Supporting Information Table of Contents 1. General

More information

Electronic Supplementary Information

Electronic Supplementary Information Electronic Supplementary Information A Novel and Facile Zn-mediated Intramolecular Five-membered Cyclization of β-tetraarylporphyrin Radicals from β-bromotetraarylporphyrins Dong-Mei Shen, Chao Liu, Qing-Yun

More information

Synthesis of cationic porphyrin modified amino. acids

Synthesis of cationic porphyrin modified amino. acids Synthesis of cationic porphyrin modified amino acids Eric Biron and Normand Voyer* Département de chimie and CREFSIP, Faculté des sciences et de génie, Université Laval, Québec, Québec, Canada G1K 7P4

More information

Rameshwar Prasad Pandit and Yong Rok Lee * School of Chemical Engineering, Yeungnam University, Gyeongsan , Korea

Rameshwar Prasad Pandit and Yong Rok Lee * School of Chemical Engineering, Yeungnam University, Gyeongsan , Korea Electronic Supplementary Material (ESI) for rganic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2014 Novel ne-pot Synthesis of Diverse γ,δ-unsaturated β-ketoesters by Thermal

More information

by Donor-Acceptor Complex

by Donor-Acceptor Complex Metal-Free C(sp 3 )-H Allylation via Aryl Carboxyl Radicals Enabled by Donor-Acceptor Complex Yang Li 1+, Jing Zhang 1+, Defang Li 1,2, and Yiyun Chen 1,2 * Supplementary Information I. General Procedures...

More information

Supporting Information

Supporting Information Supporting Information Wiley-VCH 2008 69451 Weinheim, Germany Chemoselective Peptide Cyclization via Induced Traceless Staudinger Ligation Rolf Kleineweischede, Christian P.R. Hackenberger* Institute for

More information

An efficient methodology to introduce o-(aminomethyl) phenyl-boronic acids into peptides: alkylation of secondary amines

An efficient methodology to introduce o-(aminomethyl) phenyl-boronic acids into peptides: alkylation of secondary amines Electronic Supplementary Material (ESI) for ew Journal of Chemistry. This journal is The Royal Society of Chemistry and the Centre ational de la Recherche Scientifique 2016 An efficient methodology to

More information

Highly enantioselective tandem enzyme-organocatalyst crossed aldol reactions. with acetaldehyde in deep-eutectic-solvents.

Highly enantioselective tandem enzyme-organocatalyst crossed aldol reactions. with acetaldehyde in deep-eutectic-solvents. Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 2014 Highly enantioselective tandem enzyme-organocatalyst crossed aldol reactions with acetaldehyde

More information

Supporting Information

Supporting Information Supporting Information Synthesis of N-Heteropolycyclic Compounds Including Quinazolinone Skeletons by Using Friedel-Crafts Alkylation Bu Keun Oh, Eun Bi Ko, Jin Wook Han* and Chang Ho Oh* Department of

More information

Supporting Information. Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2007

Supporting Information. Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2007 Supporting Information Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2007 Organocatalytic Asymmetric Sulfa-Michael Addition to α,β- Unsaturated Ketones Paolo Ricci, Armando Carlone, Giuseppe

More information

Chemo- and Enantioselective Rh-Catalyzed Hydrogenation of 3-Methylene-1,2-diazetidines: Application to Vicinal Diamine Synthesis

Chemo- and Enantioselective Rh-Catalyzed Hydrogenation of 3-Methylene-1,2-diazetidines: Application to Vicinal Diamine Synthesis Chemo- and Enantioselective Rh-Catalyzed Hydrogenation of 3-Methylene-1,2-diazetidines: Application to Vicinal Diamine Synthesis Greg P. Iacobini, a David W. Porter, b and Michael Shipman* a a Department

More information

Supporting information to Amino-functional polyester dendrimers based on bis-mpa as nonviral vectors for sirna delivery

Supporting information to Amino-functional polyester dendrimers based on bis-mpa as nonviral vectors for sirna delivery Supporting information to Amino-functional polyester dendrimers based on bis-mpa as nonviral vectors for sirna delivery P. Stenström, D. Manzanares, Y. Zhang, V. Ceña and M. Malkoch* * To whom correspondence

More information

Electronic Supplementary Information

Electronic Supplementary Information Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2014 Electronic Supplementary Information [Fe III (TF4DMAP)OTf] Catalysed Anti-Markovnikov Oxidation

More information

Naoya Takahashi, Keiya Hirota and Yoshitaka Saga* Supplementary material

Naoya Takahashi, Keiya Hirota and Yoshitaka Saga* Supplementary material Supplementary material Facile transformation of the five-membered exocyclic E-ring in 13 2 -demethoxycarbonyl chlorophyll derivatives by molecular oxygen with titanium oxide in the dark Naoya Takahashi,

More information

Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2008

Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2008 Experimental Details Unless otherwise noted, all chemicals were purchased from Sigma-Aldrich Chemical Company and were used as received. 2-DOS and neamine were kindly provided by Dr. F. Huang. Paromamine

More information

Supporting Information

Supporting Information Supporting Information Developing novel activity-based fluorescent probes that target different classes of proteases Qing Zhu, Aparna Girish, Souvik Chattopadhaya and Shao Q Yao * Departments of Chemistry

More information

A bidirectional synthesis of spiroacetals via Rh(II)-catalysed C H insertion

A bidirectional synthesis of spiroacetals via Rh(II)-catalysed C H insertion Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2017 Supporting Information A bidirectional synthesis of spiroacetals via Rh(II)-catalysed C H insertion

More information

Novel D-erythro N-Octanoyl Sphingosine Analogs As Chemo- and Endocrine. Resistant Breast Cancer Therapeutics

Novel D-erythro N-Octanoyl Sphingosine Analogs As Chemo- and Endocrine. Resistant Breast Cancer Therapeutics Page 11 of 32 Cancer Chemotherapy and Pharmacology Novel D-erythro N-Octanoyl Sphingosine Analogs As Chemo- and Endocrine Resistant Breast Cancer Therapeutics James W. Antoon, Jiawang Liu, Adharsh P. Ponnapakkam,

More information

Christophe Lincheneau, Bernard Jean-Denis and Thorfinnur Gunnlaugsson* Electronic Supplementary Information

Christophe Lincheneau, Bernard Jean-Denis and Thorfinnur Gunnlaugsson* Electronic Supplementary Information Self-assembly formation of mechanically interlocked [2]- and [3]catenanes using lanthanide ion [Eu(III)] templation and ring closing metathesis reactions Christophe Lincheneau, Bernard Jean-Denis and Thorfinnur

More information

Easily removable olefin metathesis catalysts

Easily removable olefin metathesis catalysts Easily removable olefin metathesis catalysts Krzysztof Skowerski,*a Celina Wierzbicka,a Grzegorz Szczepaniak,b Łukasz Gułajski, a Michał Bieniek, a and Karol Grela*b a Apeiron Synthesis Sp. z o.o., Klecińska

More information

Thermal shift binding experiments were carried out using Thermofluor 384 ELS system. Protein

Thermal shift binding experiments were carried out using Thermofluor 384 ELS system. Protein Supplementary Methods Thermal shift assays Thermal shift binding experiments were carried out using Thermofluor 384 ELS system. Protein unfolding was examined by monitoring the fluorescence of ANS (1-anilinonaphthalene-8-

More information

Supporting Information

Supporting Information Supporting Information Cobalt-Catalyzed Carbonylation of C(sp 2 )-H Bonds with Azodicarboxylate as the Carbonyl Source Jiabin Ni,, Jie Li,,š Zhoulong Fan,, and Ao Zhang *,,,š CAS Key Laboratory of Receptor

More information

Supporting Information

Supporting Information Palladium-Catalyzed Cascade Oxidantion/sp 2 C-H Acylation of Azoarenes with Aryl Methanes Feng Xiong, a Cheng Qian, b Dongen Lin, b Wei Zeng b,* and Xiaoxia Lu a,* a Chengdu Institute of Biology,CAS, Chengdu

More information

Supporting Information. for. Synthesis of 2,1-benzisoxazole-3(1H)-ones by basemediated. photochemical N O bond-forming

Supporting Information. for. Synthesis of 2,1-benzisoxazole-3(1H)-ones by basemediated. photochemical N O bond-forming Supporting Information for Synthesis of 2,1-benzisoxazole-3(1H)-ones by basemediated photochemical N O bond-forming cyclization of 2-azidobenzoic acids Daria Yu. Dzhons and Andrei V. Budruev* Address:

More information

A pillar[2]arene[3]hydroquinone which can self-assemble to a molecular zipper in the solid state

A pillar[2]arene[3]hydroquinone which can self-assemble to a molecular zipper in the solid state A pillar[2]arene[3]hydroquinone which can self-assemble to a molecular zipper in the solid state Mingguang Pan, Min Xue* Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China Fax:

More information

A multicomponent CuAAC click approach. to a library of hybrid polydentate 2-pyridyl- the generation of metallosupramolecular. architectures.

A multicomponent CuAAC click approach. to a library of hybrid polydentate 2-pyridyl- the generation of metallosupramolecular. architectures. Supporting information A multicomponent CuAAC click approach to a library of hybrid polydentate 2-pyridyl- 1,2,3-triazole ligands: New building blocks for the generation of metallosupramolecular architectures.

More information

Benzoylureas as Removable Cis Amide Inducers: Synthesis of Cyclic Amides via Ring Closing Metathesis (RCM).

Benzoylureas as Removable Cis Amide Inducers: Synthesis of Cyclic Amides via Ring Closing Metathesis (RCM). Supplementary Material (ESI) for rganic & Biomolecular Chemistry Benzoylureas as Removable Cis Amide Inducers: Synthesis of Cyclic Amides via Ring Closing Metathesis (RCM). Ryan M. Brady, Yelena Khakham,

More information

Supporting Information for

Supporting Information for Supporting Information for Ligand-directed chemistry of AMPA receptors confers live-cell fluorescent biosensors under natural habitat Shigeki Kiyonaka*, Seiji Sakamoto, Sho Wakayama, Yuma Morikawa, Muneo

More information

All chemicals were obtained from Aldrich, Acros, Fisher, or Fluka and were used without

All chemicals were obtained from Aldrich, Acros, Fisher, or Fluka and were used without Supplemental Data Alexander et al. Experimental Procedures General Methods for Inhibitor Synthesis All chemicals were obtained from Aldrich, Acros, Fisher, or Fluka and were used without further purification,

More information