2-trimethylsilylethanethiol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-bromo-5-trifluoromethyl-benzoic acid methyl ester (600 mg, 2.12 mmol, CAS RN 187331-46-0) in dioxane (6 mL) and 2-(trimethylsilyl)ethanethiol (285 mg, 335 μL, 2.12 mmol, CAS RN 18143-30-1) was stirred under argon for 5 min., treated with tris(dibenzylideneacetone)dipalladium (0) (48.5 mg, 53.0 μmol, CAS RN 52522-40-4), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (61.3 mg, 106 μmol, xantphos, CAS RN 161265-03-8) and N,N-diisopropylethylamine (548 mg, 740 μL, 4.24 mmol) and stirred at 120° C. in a sealed tube for 4 h. Stirring was continued at room temperature for another 18 hours. The reaction mixture was poured on saturated aqueous ammonium chloride solution and ethyl acetate and the layers were separated. The aqueous layer was extracted twice with ethyl acetate. The organic layers were dried over magnesium sulfate, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 20 g column using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 80:20). Yellow liquid (587 mg, 82%). MS (EI): m/z=336 ([M]). Stirring was continued at room temperature for another 18 hours the layers were separated The aqueous layer was extracted twice with ethyl acetate The organic layers were dried over magnesium sulfate filtered treated with silica gel evaporated The compound was purified by silica gel chromatography on a 20 g column eluting with a gradient of n-heptane:ethyl acetate (100:0 to 80:20)

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-bromo-4-(furan-3-yl)coumarin (Coumarin 4) (1.5 g, 5.15 mmol), 2-(trimethylsilyl)ethanethiol (830 mg, 6.18 mmol), and K2CO3 (1.77 g, 12.9 mmol) in 1-methyl-2-pyrrolidinone (12 mL) was heated at 105° C. for 4 h. After cooling, there was added saturated aqueous NH4Cl (10 mL), then H2O (50 mL) and the mixture was extracted twice with EtOAc. The organic extracts were washed 4 times with H2O, dried over MgSO4 and evaporated to a residue which was chromatographed on silica gel eluting with a 1:3 mixture of EtOAc and hexane, to afford the title compound (963 mg) as a tan solid. After cooling H2O (50 mL) and the mixture was extracted twice with EtOAc The organic extracts were washed 4 times with H2O dried over MgSO4 evaporated to a residue which was chromatographed on silica gel eluting with a 1:3 mixture of EtOAc and hexane

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-bromo-4-(furan-3-yl)coumarin (Coumarin 4) (1.5 g, 5.15 mmol), 2-(trimethylsilyl)ethanethiol (830 mg, 6.18 mmol), and K2CO3 (1.77 g, 12.9 mmol) in 1-methyl-2-pyrrolidinone (12 mL) was heated at 105° C. for 4 h. After cooling, there was added saturated aqueous NH4Cl (10 mL), then H2O (50 mL) and the mixture was extracted twice with EtOAc. The organic extracts were washed 4 times with H2O, dried over MgSO4 and evaporated to a residue which was chromatographed on silica gel eluting with a 1:3 mixture of EtOAc and hexane, to afford the title compound (963 mg) as a tan solid. After cooling H2O (50 mL) and the mixture was extracted twice with EtOAc The organic extracts were washed 4 times with H2O dried over MgSO4 evaporated to a residue which was chromatographed on silica gel eluting with a 1:3 mixture of EtOAc and hexane

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Trimethylsilylethane thiol (2.9 g, 21.9 mmol) was added dropwise to a suspension of NaH (1.8 g, 43.8 mmol) in dry DMF (60 mL) and stirred for 20 min. Then 1,3-difluoro-5-(hexafluoro-2-hydroxyprop-2-yl)benzene (Step 1 ) was added in dry DMF and the resulting reaction mixture was heated at 70° C. for 16 h. The reaction mixture was then added carefully to H2O and extracted with EtOAc. The combined organic phases were washed with brine, dried and evaporated to give a residue which was chromatographed on silica gel, eluting with 95:5 mixture of hexane:EtOAc to afford the title compound (3.2 g, 55%). the resulting reaction mixture extracted with EtOAc The combined organic phases were washed with brine dried evaporated to give a residue which was chromatographed on silica gel eluting with 95:5 mixture of hexane

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Trimethylsilylethane thiol (2.9 g, 21.9 mmol) was added dropwise to a suspension of NaH (1.8 g, 43.8 mmol) in dry DMF (60 mL) and stirred for 20 min. Then 1,3-difluoro-5-(hexafluoro-2-hydroxyprop-2-yl)benzene (Step 1 ) was added in dry DMF and the resulting reaction mixture was heated at 70° C. for 16 h. The reaction mixture was then added carefully to H2O and extracted with EtOAc. The combined organic phases were washed with brine, dried and evaporated to give a residue which was chromatographed on silica gel, eluting with 95:5 mixture of hexane:EtOAc to afford the title compound (3.2 g, 55%). the resulting reaction mixture extracted with EtOAc The combined organic phases were washed with brine dried evaporated to give a residue which was chromatographed on silica gel eluting with 95:5 mixture of hexane

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-bromo-N-(4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)-N-methyl-5-(trifluoromethyl)benzamide (0.59 g, 1.19 mmol) and 2-(trimethylsilyl)ethanethiol (159 mg, 187 μL, 1.19 mmol) in dioxane (5.9 mL) was stirred under argon for 5 minutes in a sealed tube. To the clear, light yellow solution were added tris(dibenzylideneacetone)dipalladium (0) (27.2 mg, 29.7 μmol, CAS RN 52409-22-0), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (34.3 mg, 59.3 μmol, CAS RN 161265-03-8) and DIPEA (307 mg, 414 μL, 2.37 mmol) and the reaction mixture was stirred at 120° C. for 5.5 hours, followed by stirring at room temperature overnight. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified twice by silica gel chromatography on a 20 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 50:50). Off-white solid (0.483 g; 73%). MS (ESI): m/z=551.18 [M+H]+. by stirring at room temperature overnight the layers were separated The aqueous layer was extracted twice with EtOAc The organic layers were dried over MgSO4 filtered treated with silica gel evaporated The compound was purified twice by silica gel chromatography on a 20 g column eluting with a gradient of n-heptane:EtOAc (100:0 to 50:50)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-bromo-N-(4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)-N-methyl-5-(trifluoromethyl)benzamide (0.59 g, 1.19 mmol) and 2-(trimethylsilyl)ethanethiol (159 mg, 187 μL, 1.19 mmol) in dioxane (5.9 mL) was stirred under argon for 5 minutes in a sealed tube. To the clear, light yellow solution were added tris(dibenzylideneacetone)dipalladium (0) (27.2 mg, 29.7 μmol, CAS RN 52409-22-0), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (34.3 mg, 59.3 μmol, CAS RN 161265-03-8) and DIPEA (307 mg, 414 μL, 2.37 mmol) and the reaction mixture was stirred at 120° C. for 5.5 hours, followed by stirring at room temperature overnight. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified twice by silica gel chromatography on a 20 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 50:50). Off-white solid (0.483 g; 73%). MS (ESI): m/z=551.18 [M+H]+. by stirring at room temperature overnight the layers were separated The aqueous layer was extracted twice with EtOAc The organic layers were dried over MgSO4 filtered treated with silica gel evaporated The compound was purified twice by silica gel chromatography on a 20 g column eluting with a gradient of n-heptane:EtOAc (100:0 to 50:50)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-bromo-N-(4-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)-N-methyl-5-(trifluoromethyl)benzamide (0.135 g, 279 μmol) and 2-(trimethylsilyl)ethanethiol (37.5 mg, 44.1 μL, 279 μmol) in dioxane (2 mL) was stirred under argon for 5 minutes in a sealed tube. To the clear light yellow solution were added tris(dibenzylideneacetone)dipalladium(0) (6.4 mg, 6.98 μmol, CAS RN 52409-22-0) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (8.08 mg, 14.0 μmol, CAS RN 161265-03-8) and DIPEA (72.2 mg, 97.6 μL, 559 μmol) and the reaction mixture was stirred at 120° C. After stirring for 4 hours in a sealed tube, heating was stopped. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 20 g column using an MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Colorless solid (0.116 g; 77%). MS (ESI): m/z=537.17 [M+H]+. After stirring for 4 hours in a sealed tube heating the layers were separated The aqueous layer was extracted twice with EtOAc The organic layers were dried over MgSO4 filtered treated with silica gel evaporated The compound was purified by silica gel chromatography on a 20 g column eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-cyano-1-(furan-3-yl)-6-iodonaphthalene (2.5 g, 7.25 mmol), 2-(trimethylsilyl)ethanethiol (974 mg, 7.25 mmol), potassium tert-butoxide (1.624 g, 14.5 mmol) and (Ph3P)4Pd (200 mg, 0.17 mmol) in EtOH (250 mL) was refluxed for 6.5 h. After evaporation of the EtOH, the residue was partitioned between Et2O and H2O. The crude product from the organic phase was chromatographed on silica gel, eluting with a 1:9 mixture of EtOAc and hexane to afford the title product (1.8 g) as an amber oil. was refluxed for 6.5 h After evaporation of the EtOH the residue was partitioned between Et2O and H2O The crude product from the organic phase was chromatographed on silica gel eluting with a 1:9 mixture of EtOAc and hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-cyano-1-(furan-3-yl)-6-iodonaphthalene (2.5 g, 7.25 mmol), 2-(trimethylsilyl)ethanethiol (974 mg, 7.25 mmol), potassium tert-butoxide (1.624 g, 14.5 mmol) and (Ph3P)4Pd (200 mg, 0.17 mmol) in EtOH (250 mL) was refluxed for 6.5 h. After evaporation of the EtOH, the residue was partitioned between Et2O and H2O. The crude product from the organic phase was chromatographed on silica gel, eluting with a 1:9 mixture of EtOAc and hexane to afford the title product (1.8 g) as an amber oil. was refluxed for 6.5 h After evaporation of the EtOH the residue was partitioned between Et2O and H2O The crude product from the organic phase was chromatographed on silica gel eluting with a 1:9 mixture of EtOAc and hexane