(1-chloro-2-methylpropyl) 2-methylpropanoate

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

Procedure: The title compound was prepared according to the procedure as described in Example 14 Step 2 using N-(3-(5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide (0.3 g, 0.61 mmol) in anhydrous DMF (2.5 mL), KOH (69 mg, 1.23 mmol) and a solution of 1-chloro-2-methylpropyl isobutyrate (108 mg, 0.61 mmol) in anhydrous DMF (0.5 mL). The crude product was purified by a silica gel column chromatography (PE/EtOAc (v/v)=4/1), and recrystallized in methanol to afford the title compound as a white solid (47 mg, 13.4%). The title compound was characterized by LC-MS and 1H NMR as shown below: The title compound was prepared The crude product was purified by a silica gel column chromatography (PE/EtOAc (v/v)=4/1) recrystallized in methanol

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

Procedure: To a mixture of isobutyryl chloride (10 mL, 94.7 mmol) and zinc (II) chloride (25 mg, 186 mmol) was added isobutyraldehyde (10.4 mL, 113.6 mmol) at −20° C. The reaction was stirred at 0° C. for 1 h, then at rt for another 2 h. The mixture was filtered through a short silica gel column (100% PE). The solution was concentrated in vacuo at 40° C. and the resulted oil was distilled at 75° C. under reduced pressure to give the title compound as colorless oil (13.48 g, 79.3%). The title compound was characterized by 1H NMR as shown below: at rt for another 2 h The mixture was filtered through a short silica gel column (100% PE) The solution was concentrated in vacuo at 40° C. the resulted oil was distilled at 75° C. under reduced pressure

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

Procedure: To a mixture of isobutyryl chloride (10 mL, 94.7 mmol) and zinc (II) chloride (25 mg, 186 mmol) was added isobutyraldehyde (10.4 mL, 113.6 mmol) at −20° C. The reaction was stirred at 0° C. for 1 h, then at rt for another 2 h. The mixture was filtered through a short silica gel column (100% PE). The solution was concentrated in vacuo at 40° C. and the resulted oil was distilled at 75° C. under reduced pressure to give the title compound as colorless oil (13.48 g, 79.3%). The title compound was characterized by 1H NMR as shown below: at rt for another 2 h The mixture was filtered through a short silica gel column (100% PE) The solution was concentrated in vacuo at 40° C. the resulted oil was distilled at 75° C. under reduced pressure

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

Procedure: The title compound was prepared according to the procedure as described in Example 14 Step 2 using N-(3-(5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide (0.3 g, 0.61 mmol) in anhydrous DMF (2.5 mL), KOH (69 mg, 1.23 mmol) and a solution of 1-chloro-2-methylpropyl isobutyrate (108 mg, 0.61 mmol) in anhydrous DMF (0.5 mL). The crude product was purified by a silica gel column chromatography (PE/EtOAc (v/v)=4/1), and recrystallized in methanol to afford the title compound as a white solid (47 mg, 13.4%). The title compound was characterized by LC-MS and 1H NMR as shown below: The title compound was prepared The crude product was purified by a silica gel column chromatography (PE/EtOAc (v/v)=4/1) recrystallized in methanol

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

Procedure: To a mixture of isobutyryl chloride (10 mL, 94.7 mmol) and zinc (II) chloride (25 mg, 186 mmol) was added isobutyraldehyde (10.4 mL, 113.6 mmol) at −20° C. The reaction was stirred at 0° C. for 1 h, then at rt for another 2 h. The mixture was filtered through a short silica gel column (100% PE). The solution was concentrated in vacuo at 40° C. and the resulted oil was distilled at 75° C. under reduced pressure to give the title compound as colorless oil (13.48 g, 79.3%). The title compound was characterized by 1H NMR as shown below: at rt for another 2 h The mixture was filtered through a short silica gel column (100% PE) The solution was concentrated in vacuo at 40° C. the resulted oil was distilled at 75° C. under reduced pressure