(R)-1-(2-氯苯基)乙醇

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

实验步骤: In analogy to the procedure described for the synthesis of 5-tert-butyl-2-[(R)-1-(2-chloro-phenyl)-ethyl]-7-(3,3-difluoro-pyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 87), the title compound was prepared from 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and (R)-1-(2-chlorophenyl)ethanol and isolated as light-yellow gum (3.8 mg, 21%). MS (m/e): 421.4 (MH+).

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (10 g, 35 mmol), (R)-1-(2-chloro-phenyl)-ethanol (6.6 g, 42 mmol), triethylamine (10 mL, 70 mmol), and diphenylphosphoryl azide (11.5 g, 42 mmol) were combined in toluene (100 mL) and stirred at 90° C. for 1 hour. The mixture was concentrated, and the residue was purified by silica gel chromatography (0-30% EtOAc in hexanes). The isolated product was recrystallized in 5:1 hexanes:acetone to give the title compound in >99% e.e (by chiral HPLC. Chiracel OD 98.4% hexanes/1.6% Ethanol. Major isomer 27.9 min minor isomer 32.7 min). The mixture was concentrated the residue was purified by silica gel chromatography (0-30% EtOAc in hexanes) The isolated product was recrystallized in 5:1 hexanes

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

实验步骤: 2′-Chloroacetophenone (8.4 mL, 65 mmol) and (S)-(−)-2-methyl-CBS-oxazaborolidine (0.90 g, 0.32 mmol) were combined in THF (75 mL). Borane methyl sulfide complex (2M in THF; 21.5 mL, 43 mmol) was added over 20 minutes, and the reaction was stirred at room temperature for 30 minutes. MeOH was added, and the mixture was worked-up with CH2Cl2 and H2O. The organic layer was concentrated to give the title compound. The organic layer was concentrated

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

实验步骤: 2′-Chloroacetophenone (8.4 mL, 65 mmol) and (S)-(−)-2-methyl-CBS-oxazaborolidine (0.90 g, 0.32 mmol) were combined in THF (75 mL). Borane methyl sulfide complex (2M in THF; 21.5 mL, 43 mmol) was added over 20 minutes, and the reaction was stirred at room temperature for 30 minutes. MeOH was added, and the mixture was worked-up with CH2Cl2 and H2O. The organic layer was concentrated to give the title compound. The organic layer was concentrated

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

实验步骤: In analogy to the procedure described for the synthesis of 5-tert-butyl-2-[(R)-1-(2-chloro-phenyl)-ethyl]-7-(3,3-difluoro-pyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 87), the title compound was prepared from 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and (R)-1-(2-chlorophenyl)ethanol and isolated as light-yellow gum (3.8 mg, 21%). MS (m/e): 421.4 (MH+).

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

实验步骤: In analogy to the procedure described for the synthesis of 5-tert-butyl-2-[(R)-1-(2-chloro-phenyl)-ethyl]-7-(3,3-difluoro-pyrrolidin-1-yl)-2H-[1,2,3]triazolo[4,5-d]pyrimidine (example 28), the title compound was prepared from 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and (R)-1-(2-chlorophenyl)ethanol and isolated as white solid (3.7 mg, 21%). MS (m/e): 421.4 (MH+).

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

实验步骤: In analogy to the procedure described for the synthesis of 5-tert-butyl-2-[(R)-1-(2-chloro-phenyl)-ethyl]-7-(3,3-difluoro-pyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 87), the title compound was prepared from 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and (R)-1-(2-chlorophenyl)ethanol and isolated as light-yellow gum (3.8 mg, 21%). MS(m/e): 421.4 (MH+).

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

实验步骤: According to methods similar to those of Step 5 and Step 6 of Example 19 using 3-(4-iodophenyl)isoxazole-4-carboxylic acid and (R)-2-chloro-α-methylbenzyl alcohol, methyl 5-(4-{4-[(1R)-1-(2-chlorophenyl)ethoxycarbonylamino]-3-isoxazolyl}phenyl)-4-pentenoate was synthesized, which was reacted in the same manner as in Example 2 to give the title compound. was synthesized which was reacted in the same manner as in Example 2

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

实验步骤: Reaction was carried out using 2′-chloroacetophenone (11.90 g, 76.77 mmol) and (+)-B-chlorodiisopinocamphenylborane ((+)-DIP-C1) (25.00 g, 77.88 mmol) and according to J. Org. Chem., 1985, vol. 50, p. 5446; and 1988, vol. 53, p. 2916, to give the title compound (8.81 g, 72%). The optical purity was determined by HPLC analysis using an optically active column after conversion to the acetate (using acetic anhydride and triethylamine in dichloromethane). Reaction

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (10 g, 35 mmol), (R)-1-(2-chloro-phenyl)-ethanol (6.6 g, 42 mmol), triethylamine (10 mL, 70 mmol), and diphenylphosphoryl azide (11.5 g, 42 mmol) were combined in toluene (100 mL) and stirred at 90° C. for 1 hour. The mixture was concentrated, and the residue was purified by silica gel chromatography (0-30% EtOAc in hexanes). The isolated product was recrystallized in 5:1 hexanes:acetone to give the title compound in >99% e.e (by chiral HPLC. Chiracel OD 98.4% hexanes/1.6% Ethanol. Major isomer 27.9 min minor isomer 32.7 min) The mixture was concentrated the residue was purified by silica gel chromatography (0-30% EtOAc in hexanes) The isolated product was recrystallized in 5:1 hexanes

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

实验步骤: 2′-Chloroacetophenone (8.4 mL, 65 mmol) and (S)-(−)-2-methyl-CBS-oxazaborolidine (0.90 g, 0.32 mmol) were combined in THF (75 mL). Borane methyl sulfide complex (2M in THF; 21.5 mL, 43 mmol) was added over 20 minutes, and the reaction was stirred at room temperature for 30 minutes. MeOH was added, and the mixture was worked-up with CH2Cl2 and H2O. The organic layer was concentrated to give the title compound. The organic layer was concentrated

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (10 g, 35 mmol), (R)-1-(2-chloro-phenyl)-ethanol (6.6 g, 42 mmol), triethylamine (10 mL, 70 mmol), and diphenylphosphoryl azide (11.5 g, 42 mmol) were combined in toluene (100 mL) and stirred at 90° C. for 1 hour. The mixture was concentrated, and the residue was purified by silica gel chromatography (0-30% EtOAc in hexanes). The isolated product was recrystallized in 5:1 hexanes:acetone to give the title compound in >99% e.e (by chiral HPLC. Chiracel OD 98.4% hexanes/1.6% Ethanol. Major isomer 27.9 min minor isomer 32.7 min). The mixture was concentrated the residue was purified by silica gel chromatography (0-30% EtOAc in hexanes) The isolated product was recrystallized in 5:1 hexanes