1-methoxy-2-methylpropan-2-ol

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

Procedure: 1-Methoxy-2-methyl-2-propanol (3.50 ml, 30 mmol) was treated with 4-nitrophenyl chloroformate according to conditions similar to the ones described above with respect to Intermediate 2, Step 2 to provide, after purification by column chromatography over silica gel (eluting with Hexanes/EtOAc 99:1 to 70:30), 1-methoxy-2-methylpropan-2-yl 4-nitrophenyl carbonate (7.02 g, 87% yield) as a colorless oil. 1H-NMR (300 MHz, CDCl3) δ 8.26 (d, J=9.2 Hz, 2H), 7.36 (d, J=9.2 Hz, 2H), 3.56 (s, 3H), 3.43 (s, 3H), 1.57 (s, 6H). to provide

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

Procedure: A solution of 1-methoxy-2-methyl-2-propanol (91 mg, 0.88 mmol) in THF (1.5 mL) and TEA (0.20 mL, 1.4 mmol) was cooled to 0° C. and allowed to stir. Triphosgene (260 mg, 0.876 mmol) was added and the resulting mixture was allowed to warm to ambient temperature and was stirred for 15 minutes. A solution of 4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-5) (80 mg, 0.18 mmol) and TEA (0.061 mL, 0.44 mmol) in DCM (1.0 mL) was then added to the reaction mixture dropwise. The resulting mixture was heated to 50° C. and allowed to stir for 16 hours. The solution was cooled to ambient temperature, diluted with DCM, washed with water, dried over anhydrous MgSO4, and concentrated in vacuo. The resulting residue was purified by MPLC on silica gel (using a gradient elution of 0-10% MeOH/DCM) to afford the title compound, Example #28. was stirred for 15 minutes The resulting mixture was heated to 50° C. to stir for 16 hours The solution was cooled to ambient temperature washed with water dried over anhydrous MgSO4 concentrated in vacuo The resulting residue was purified by MPLC on silica gel ( a gradient elution of 0-10% MeOH/DCM)

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

Procedure: A solution of 1-methoxy-2-methyl-2-propanol (91 mg, 0.88 mmol) in THF (1.5 mL) and TEA (0.20 mL, 1.4 mmol) was cooled to 0° C. and allowed to stir. Triphosgene (260 mg, 0.876 mmol) was added and the resulting mixture was allowed to warm to ambient temperature and was stirred for 15 minutes. A solution of 4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-5) (80 mg, 0.18 mmol) and TEA (0.061 mL, 0.44 mmol) in DCM (1.0 mL) was then added to the reaction mixture dropwise. The resulting mixture was heated to 50° C. and allowed to stir for 16 hours. The solution was cooled to ambient temperature, diluted with DCM, washed with water, dried over anhydrous MgSO4, and concentrated in vacuo. The resulting residue was purified by MPLC on silica gel (using a gradient elution of 0-10% MeOH/DCM) to afford the title compound, Example #28. was stirred for 15 minutes The resulting mixture was heated to 50° C. to stir for 16 hours The solution was cooled to ambient temperature washed with water dried over anhydrous MgSO4 concentrated in vacuo The resulting residue was purified by MPLC on silica gel ( a gradient elution of 0-10% MeOH/DCM)

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

Procedure: 1-Methoxy-2-methyl-2-propanol (3.50 ml, 30 mmol) was treated with 4-nitrophenyl chloroformate according to conditions similar to the ones described above with respect to Intermediate 2, Step 2 to provide, after purification by column chromatography over silica gel (eluting with Hexanes/EtOAc 99:1 to 70:30), 1-methoxy-2-methylpropan-2-yl 4-nitrophenyl carbonate (7.02 g, 87% yield) as a colorless oil. 1H-NMR (300 MHz, CDCl3) δ 8.26 (d, J=9.2 Hz, 2H), 7.36 (d, J=9.2 Hz, 2H), 3.56 (s, 3H), 3.43 (s, 3H), 1.57 (s, 6H). to provide

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

Procedure: A solution of 1-methoxy-2-methyl-2-propanol (91 mg, 0.88 mmol) in THF (1.5 mL) and TEA (0.20 mL, 1.4 mmol) was cooled to 0° C. and allowed to stir. Triphosgene (260 mg, 0.876 mmol) was added and the resulting mixture was allowed to warm to ambient temperature and was stirred for 15 minutes. A solution of 4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-5) (80 mg, 0.18 mmol) and TEA (0.061 mL, 0.44 mmol) in DCM (1.0 mL) was then added to the reaction mixture dropwise. The resulting mixture was heated to 50° C. and allowed to stir for 16 hours. The solution was cooled to ambient temperature, diluted with DCM, washed with water, dried over anhydrous MgSO4, and concentrated in vacuo. The resulting residue was purified by MPLC on silica gel (using a gradient elution of 0-10% MeOH/DCM) to afford the title compound, Example #28. was stirred for 15 minutes The resulting mixture was heated to 50° C. to stir for 16 hours The solution was cooled to ambient temperature washed with water dried over anhydrous MgSO4 concentrated in vacuo The resulting residue was purified by MPLC on silica gel ( a gradient elution of 0-10% MeOH/DCM)