(1-fluorocyclohexyl)methanol

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add triphosgene (246 mg, 0.79 mmol) at room temperature to a solution of (3S,5R)-5-[(1R,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-3-methylmorpholin-2-ol (1 g, 1.75 mmol) and triethylamine (0.99 mL, 7 mmol) in anhydrous dichloromethane (17 mL). Stir for 30 min, cool to 0° C. and add (1-fluorocyclohexyl)-methanol (1.16 g, 8.75 mmol) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) (0.64 mL, 3.5 mmol). Stir at 0° C. for 1 hour and at room temperature for 2 hours. Add more trimethylsilyl trifluoromethanesulfonate (0.16 mL, 0.87 mmol) and stir at room temperature for 30 min. Add 10% aqueous potassium carbonate, separate the organic layer and extract the aqueous layer with dichloromethane. Combine the organic layers, dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 20:80 hexanes:ethyl acetate), to give the title compound as a colorless oil (375 mg). Stir at 0° C. for 1 hour and at room temperature for 2 hours stir at room temperature for 30 min separate the organic layer extract the aqueous layer with dichloromethane dry (sodium sulfate) filter concentrate purify (silica gel chromatography, eluting with 0:100 to 20:80 hexanes:ethyl acetate)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add triphosgene (246 mg, 0.79 mmol) at room temperature to a solution of (3S,5R)-5-[(1R,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-3-methylmorpholin-2-ol (1 g, 1.75 mmol) and triethylamine (0.99 mL, 7 mmol) in anhydrous dichloromethane (17 mL). Stir for 30 min, cool to 0° C. and add (1-fluorocyclohexyl)-methanol (1.16 g, 8.75 mmol) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) (0.64 mL, 3.5 mmol). Stir at 0° C. for 1 hour and at room temperature for 2 hours. Add more trimethylsilyl trifluoromethanesulfonate (0.16 mL, 0.87 mmol) and stir at room temperature for 30 min. Add 10% aqueous potassium carbonate, separate the organic layer and extract the aqueous layer with dichloromethane. Combine the organic layers, dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 20:80 hexanes:ethyl acetate), to give the title compound as a colorless oil (375 mg). Stir at 0° C. for 1 hour and at room temperature for 2 hours stir at room temperature for 30 min separate the organic layer extract the aqueous layer with dichloromethane dry (sodium sulfate) filter concentrate purify (silica gel chromatography, eluting with 0:100 to 20:80 hexanes:ethyl acetate)

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

Procedure: Following the procedure as described in Example 8 and making variations as required to replace 5-chloro-2,4-difluoro-N-(methylsulfonyl)benzamide with 5-chloro-N—(N,N-dimethylsulfamoyl)-2,4-difluorobenzamide and adamantan-1-ylmethanol with (1-fluorocyclohexyl)methanol, the title compound was obtained as a colorless solid (0.08 g, 19%): 1H NMR (300 MHz, DMSO-d6) δ 11.79 (s, 1H), 7.75 (d, J=7.4 Hz, 1H), 7.30 (d, J=12.3 Hz, 1H), 4.24 (d, J=21.2 Hz, 2H), 2.88 (s, 6H), 1.96-1.87 (m, 2H), 1.72-1.50 (m, 7H), 1.37-1.24 (m, 1H); MS (ES−) m/z 409.1, 411.1 (M−1).

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

Procedure: Following the procedure as described in Example 8 and making variations as required to replace 5-chloro-2,4-difluoro-N-(methylsulfonyl)benzamide with 5-chloro-N—(N,N-dimethylsulfamoyl)-2,4-difluorobenzamide and adamantan-1-ylmethanol with (1-fluorocyclohexyl)methanol, the title compound was obtained as a colorless solid (0.08 g, 19%): 1H NMR (300 MHz, DMSO-d6) δ 11.79 (s, 1H), 7.75 (d, J=7.4 Hz, 1H), 7.30 (d, J=12.3 Hz, 1H), 4.24 (d, J=21.2 Hz, 2H), 2.88 (s, 6H), 1.96-1.87 (m, 2H), 1.72-1.50 (m, 7H), 1.37-1.24 (m, 1H); MS (ES−) m/z 409.1, 411.1 (M−1).

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

Procedure: Starting with 4-(2,4-difluorophenyl)-N-{3-[(methylsulfonyl)methyl]phenyl}-1,3,5-triazin-2-amine (80 mg; 0.21 mmol), intermediate 42.1, and (1-fluorocyclohexyl)methanol (117 mg; 0.841 mmol), example 66 was prepared analogously to the procedure for the preparation of example 42. was prepared analogously to the procedure for the preparation of example 42

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add triphosgene (246 mg, 0.79 mmol) at room temperature to a solution of (3S,5R)-5-[(1R,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-3-methylmorpholin-2-ol (1 g, 1.75 mmol) and triethylamine (0.99 mL, 7 mmol) in anhydrous dichloromethane (17 mL). Stir for 30 min, cool to 0° C. and add (1-fluorocyclohexyl)-methanol (1.16 g, 8.75 mmol) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) (0.64 mL, 3.5 mmol). Stir at 0° C. for 1 hour and at room temperature for 2 hours. Add more trimethylsilyl trifluoromethanesulfonate (0.16 mL, 0.87 mmol) and stir at room temperature for 30 min. Add 10% aqueous potassium carbonate, separate the organic layer and extract the aqueous layer with dichloromethane. Combine the organic layers, dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 20:80 hexanes:ethyl acetate), to give the title compound as a colorless oil (375 mg). Stir at 0° C. for 1 hour and at room temperature for 2 hours stir at room temperature for 30 min separate the organic layer extract the aqueous layer with dichloromethane dry (sodium sulfate) filter concentrate purify (silica gel chromatography, eluting with 0:100 to 20:80 hexanes:ethyl acetate)