1-chloro-3-methylbutan-2-one

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

Procedure: To a 0° C. solution of example 1, (4-{4-[({3-tert-butyl-1-[3-(hydroxymethyl)phenyl]-1H-pyrazol-5-yl}carbamoyl)amino]-3-fluorophenoxy}-N-methylpyridine-2-carboxamide, (0.10 g, 0.19 mmol) in dichloromethane (1.0 mL)/pyridine (0.3 mL) was added dropwise 3-methylbutanonyl chloride (0.02 mL, 0.23 mmol). The reaction mixture was allowed to warm to room temperature and stir for 72 h. The reaction mixture was diluted with EtOAc and washed with sat. aqueous NaHCO3. The combined organic layer was washed with brine, dried and concentrated. The crude material was purified via column chromatography (CH2Cl2: MeOH, 100% CH2Cl2 to 98.5:1.5) to afford 0.02 g (18%) of the desired product as a white solid. MS m/z 617.3 (M+H)+; Retention time (LC-MS): 3.89 min. washed with sat. aqueous NaHCO3 The combined organic layer was washed with brine dried concentrated The crude material was purified via column chromatography (CH2Cl2: MeOH, 100% CH2Cl2 to 98.5:1.5)

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

Procedure: To a 0° C. solution of example 1, (4-{4-[({3-tert-butyl-1-[3-(hydroxymethyl)phenyl]-1H-pyrazol-5-yl}carbamoyl)amino]-3-fluorophenoxy}-N-methylpyridine-2-carboxamide, (0.10 g, 0.19 mmol) in dichloromethane (1.0 mL)/pyridine (0.3 mL) was added dropwise 3-methylbutanonyl chloride (0.02 mL, 0.23 mmol). The reaction mixture was allowed to warm to room temperature and stir for 72 h. The reaction mixture was diluted with EtOAc and washed with sat. aqueous NaHCO3. The combined organic layer was washed with brine, dried and concentrated. The crude material was purified via column chromatography (CH2Cl2: MeOH, 100% CH2Cl2 to 98.5:1.5) to afford 0.02 g (18%) of the desired product as a white solid. MS m/z 617.3 (M+H)+; Retention time (LC-MS): 3.89 min. washed with sat. aqueous NaHCO3 The combined organic layer was washed with brine dried concentrated The crude material was purified via column chromatography (CH2Cl2: MeOH, 100% CH2Cl2 to 98.5:1.5)

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

Procedure: To a 0° C. solution of example 1, (4-{4-[({3-tert-butyl-1-[3-(hydroxymethyl)phenyl]-1H-pyrazol-5-yl}carbamoyl)amino]-3-fluorophenoxy}-N-methylpyridine-2-carboxamide, (0.10 g, 0.19 mmol) in dichloromethane (1.0 mL)/pyridine (0.3 mL) was added dropwise 3-methylbutanonyl chloride (0.02 mL, 0.23 mmol). The reaction mixture was allowed to warm to room temperature and stir for 72 h. The reaction mixture was diluted with EtOAc and washed with sat. aqueous NaHCO3. The combined organic layer was washed with brine, dried and concentrated. The crude material was purified via column chromatography (CH2Cl2: MeOH, 100% CH2Cl2 to 98.5:1.5) to afford 0.02 g (18%) of the desired product as a white solid. MS m/z 617.3 (M+H)+; Retention time (LC-MS): 3.89 min. washed with sat. aqueous NaHCO3 The combined organic layer was washed with brine dried concentrated The crude material was purified via column chromatography (CH2Cl2: MeOH, 100% CH2Cl2 to 98.5:1.5)

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

Procedure: To a 0° C. solution of example 1, (4-{4-[({3-tert-butyl-1-[3-(hydroxymethyl)phenyl]-1H-pyrazol-5-yl}carbamoyl)amino]-3-fluorophenoxy}-N-methylpyridine-2-carboxamide, (0.10 g, 0.19 mmol) in dichloromethane (1.0 mL)/pyridine (0.3 mL) was added dropwise 3-methylbutanonyl chloride (0.02 mL, 0.23 mmol). The reaction mixture was allowed to warm to room temperature and stir for 72 h. The reaction mixture was diluted with EtOAc and washed with sat. aqueous NaHCO3. The combined organic layer was washed with brine, dried and concentrated. The crude material was purified via column chromatography (CH2Cl2: MeOH, 100% CH2Cl2 to 98.5:1.5) to afford 0.02 g (18%) of the desired product as a white solid. MS m/z 617.3 (M+H)+; Retention time (LC-MS): 3.89 min. washed with sat. aqueous NaHCO3 The combined organic layer was washed with brine dried concentrated The crude material was purified via column chromatography (CH2Cl2: MeOH, 100% CH2Cl2 to 98.5:1.5)