双[Α,Α-双(三氟甲基)苯甲醇合]二苯硫

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (±)-2-(trans-2-Hydroxycyclohexyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 508, 78 mg, 0.18 mmol) was suspended in dichloromethane (3 mL) and treated with bis[α,α-bis(trifluoromethyl)benzyloxy]diphenylsulfur (Martin's sulfurane, 0.18 g, 0.27 mmol, 1.5 equiv). After stirring for 1 hour, additional Martin's sulfurane (75 mg, 0.18 mmol, 1 equiv) was added and the mixture was stirred at ambient temperature for an additional 16 hours. The mixture was then placed into an oil bath preheated to 45° C. for 6 hours, cooled to ambient temperature, treated with sodium bicarbonate (1.5 mL, aqueous saturated) and stirred vigorously for 30 minutes. The mixture was poured into sodium bicarbonate (50 mL, aqueous saturated) and extracted with dichloromethane (2×75 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 90:10; dichloromethane:methanol), providing partially purified material. The mixture was purified by preparative reverse phase HPLC (80:20 to 25:75; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid). The appropriate fractions were poured into sodium bicarbonate (15 mL, aqueous saturated) and extracted once with ethyl acetate (30 mL). The organic layer was dried with sodium sulfate, filtered and concentrated in vacuo, providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.44 (1H, dd, J=4.6, 2.0 Hz), 8.42 (1H, s), 7.89 (1H, d, J=2.6 Hz), 7.72 (1H, d, J=1.8 Hz), 7.70 (2H, d, J=8.6 Hz), 7.46-7.43 (2H, m), 7.41-7.37 (1H, m), 7.28-7.28 (2H, m), 6.47 (1H, dd, J=2.4, 1.9 Hz), 6.03-5.98 (1H, m), 5.75 (1H, br d, J=9.8 Hz), 5.47 (2H, s), 5.29-5.22 (1H, m), 2.30-2.20 (1H, m), 2.14-1.98 (4H, m), 1.85-1.73 (1H, m) ppm; high resolution mass spectrometry (ES+) m/z 422.1981 [(M+H)+; calculated for C26H24N5O: 422.1975]. the mixture was stirred at ambient temperature for an additional 16 hours The mixture was then placed into an oil bath preheated to 45° C. for 6 hours stirred vigorously for 30 minutes extracted with dichloromethane (2×75 mL) The combined organic extracts were dried with sodium sulfate filtered concentrated in vacuo The residue was purified by silica gel gradient chromatography (100:0 90:10; dichloromethane:methanol) providing partially purified material The mixture was purified by preparative reverse phase HPLC (80:20 to 25:75; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid) The appropriate fractions were poured into sodium bicarbonate (15 mL, aqueous saturated) extracted once with ethyl acetate (30 mL) The organic layer was dried with sodium sulfate filtered concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (±)-2-(trans-2-Hydroxycyclohexyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 508, 78 mg, 0.18 mmol) was suspended in dichloromethane (3 mL) and treated with bis[α,α-bis(trifluoromethyl)benzyloxy]diphenylsulfur (Martin's sulfurane, 0.18 g, 0.27 mmol, 1.5 equiv). After stirring for 1 hour, additional Martin's sulfurane (75 mg, 0.18 mmol, 1 equiv) was added and the mixture was stirred at ambient temperature for an additional 16 hours. The mixture was then placed into an oil bath preheated to 45° C. for 6 hours, cooled to ambient temperature, treated with sodium bicarbonate (1.5 mL, aqueous saturated) and stirred vigorously for 30 minutes. The mixture was poured into sodium bicarbonate (50 mL, aqueous saturated) and extracted with dichloromethane (2×75 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 90:10; dichloromethane:methanol), providing partially purified material. The mixture was purified by preparative reverse phase HPLC (80:20 to 25:75; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid). The appropriate fractions were poured into sodium bicarbonate (15 mL, aqueous saturated) and extracted once with ethyl acetate (30 mL). The organic layer was dried with sodium sulfate, filtered and concentrated in vacuo, providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.44 (1H, dd, J=4.6, 2.0 Hz), 8.42 (1H, s), 7.89 (1H, d, J=2.6 Hz), 7.72 (1H, d, J=1.8 Hz), 7.70 (2H, d, J=8.6 Hz), 7.46-7.43 (2H, m), 7.41-7.37 (1H, m), 7.28-7.28 (2H, m), 6.47 (1H, dd, J=2.4, 1.9 Hz), 6.03-5.98 (1H, m), 5.75 (1H, br d, J=9.8 Hz), 5.47 (2H, s), 5.29-5.22 (1H, m), 2.30-2.20 (1H, m), 2.14-1.98 (4H, m), 1.85-1.73 (1H, m) ppm; high resolution mass spectrometry (ES+) m/z 422.1981 [(M+H)+; calculated for C26H24N5O: 422.1975]. the mixture was stirred at ambient temperature for an additional 16 hours The mixture was then placed into an oil bath preheated to 45° C. for 6 hours stirred vigorously for 30 minutes extracted with dichloromethane (2×75 mL) The combined organic extracts were dried with sodium sulfate filtered concentrated in vacuo The residue was purified by silica gel gradient chromatography (100:0 90:10; dichloromethane:methanol) providing partially purified material The mixture was purified by preparative reverse phase HPLC (80:20 to 25:75; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid) The appropriate fractions were poured into sodium bicarbonate (15 mL, aqueous saturated) extracted once with ethyl acetate (30 mL) The organic layer was dried with sodium sulfate filtered concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3β-benzoyloxy-14α-cyano-4,4-di-methyl-5α-cholestan-7-ol (100 mg, 0.18 mmole) prepared as in Example 13(iv), in dichloromethane (2.5 mL) held at -78° C. was added Martin sulfurane dehydrating agent (bis [α,α-bis(trifluoromethyl)benzenemethanolato]-diphenyl-sulfur) (240 mg, 0.36 mmole) in dichloromethane (2.5 mL). The mixture was warmed to ambient temperature, stirred for an additional 6 hours, concentrated in vacuo and the residue was triturated with methanol to give 3β-benzoyloxy-14α-cyano-4,4-dimethyl-5α-cholest-6-ene (80 mg, 82%); mp 232°-233° C. (from CH2Cl2/MeOH). held at -78° C. concentrated in vacuo the residue was triturated with methanol

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (±)-2-(trans-2-Hydroxycyclohexyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 508, 78 mg, 0.18 mmol) was suspended in dichloromethane (3 mL) and treated with bis[α,α-bis(trifluoromethyl)benzyloxy]diphenylsulfur (Martin's sulfurane, 0.18 g, 0.27 mmol, 1.5 equiv). After stirring for 1 hour, additional Martin's sulfurane (75 mg, 0.18 mmol, 1 equiv) was added and the mixture was stirred at ambient temperature for an additional 16 hours. The mixture was then placed into an oil bath preheated to 45° C. for 6 hours, cooled to ambient temperature, treated with sodium bicarbonate (1.5 mL, aqueous saturated) and stirred vigorously for 30 minutes. The mixture was poured into sodium bicarbonate (50 mL, aqueous saturated) and extracted with dichloromethane (2×75 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 90:10; dichloromethane:methanol), providing partially purified material. The mixture was purified by preparative reverse phase HPLC (80:20 to 25:75; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid). The appropriate fractions were poured into sodium bicarbonate (15 mL, aqueous saturated) and extracted once with ethyl acetate (30 mL). The organic layer was dried with sodium sulfate, filtered and concentrated in vacuo, providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.44 (1H, dd, J=4.6, 2.0 Hz), 8.42 (1H, s), 7.89 (1H, d, J=2.6 Hz), 7.72 (1H, d, J=1.8 Hz), 7.70 (2H, d, J=8.6 Hz), 7.46-7.43 (2H, m), 7.41-7.37 (1H, m), 7.28-7.28 (2H, m), 6.47 (1H, dd, J=2.4, 1.9 Hz), 6.03-5.98 (1H, m), 5.75 (1H, br d, J=9.8 Hz), 5.47 (2H, s), 5.29-5.22 (1H, m), 2.30-2.20 (1H, m), 2.14-1.98 (4H, m), 1.85-1.73 (1H, m) ppm; high resolution mass spectrometry (ES+) m/z 422.1981 [(M+H)+; calculated for C26H24N5O: 422.1975]. the mixture was stirred at ambient temperature for an additional 16 hours The mixture was then placed into an oil bath preheated to 45° C. for 6 hours stirred vigorously for 30 minutes extracted with dichloromethane (2×75 mL) The combined organic extracts were dried with sodium sulfate filtered concentrated in vacuo The residue was purified by silica gel gradient chromatography (100:0 90:10; dichloromethane:methanol) providing partially purified material The mixture was purified by preparative reverse phase HPLC (80:20 to 25:75; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid) The appropriate fractions were poured into sodium bicarbonate (15 mL, aqueous saturated) extracted once with ethyl acetate (30 mL) The organic layer was dried with sodium sulfate filtered concentrated in vacuo