1-(dimethylamino)propan-2-one

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

Procedure: (4Z)-6-Iodo-4-{[(4-piperazin-1-ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione (47.4 mg, 0.1 mmol) is dissolved in N-methylpyrrolidinone (1 mL) and methylene chloride (0.3 mL), followed by addition of sodium triacetoxyborohydride (244 mg, 1.15 mmol), 1-dimethylamino-propan-2-one (0.296 mL, 2.58 mmol) and acetic acid (0.15 mL, 2.6 mmol). After stirring at room temperature for 40 min, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 32 mg (57%) of the title compound as a yellow solid. MS (ESI) m/z 560.4 (M+H)+1. The organic layer is separated dried

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

Procedure: (4Z)-6-Iodo-4-{[(4-piperazin-1-ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione (47.4 mg, 0.1 mmol) is dissolved in N-methylpyrrolidinone (1 mL) and methylene chloride (0.3 mL), followed by addition of sodium triacetoxyborohydride (244 mg, 1.15 mmol), 1-dimethylamino-propan-2-one (0.296 mL, 2.58 mmol) and acetic acid (0.15 mL, 2.6 mmol). After stirring at room temperature for 40 min, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 32 mg (57%) of the title compound as a yellow solid. MS (ESI) m/z 560.4 (M+H)+1. The organic layer is separated dried

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

Procedure: To a solution of 4-amino-N-[5-(3,5-difluoro-benzenesulfonyl)-1-trityl-1H-indazol-3-yl]-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzamide (1.56 g, 1.8 mmol) in dichloromethane (30 mL) was added trifluoroacetic acid (2.78 mL, 36 mmol), tetramethylammonium triacetoxyborohydride (710 mg, 2.7 mmol) and 1-dimethylamino-propan-2-one (316 microL, 2.7 mmol). The mixture was stirred at room temperature overnight then additional tetramethylammonium triacetoxyborohydride (710 mg, 2.7 mmol) and 1-dimethylamino-propan-2-one (316 microL, 2.7 mmol) were added. The mixture was heated at reflux and stirred for additional 6 hours. After evaporation of the volatiles, the residue was chromatographed on silica gel eluting with dichloromethane/methanol/triethylamine 90:10:0.1 affording 845 mg of N-[5-(3,5-difluoro-benzenesulfonyl)-1H-indazol-3-yl]-4-(2-dimethylamino-1-methyl-ethylamino)-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzamide that was dissolved in methanol (5 mL) and triethylamine (2 mL) and stirred at 50° C. for 6 hours. The mixture was then evaporated to dryness and the residue purified by flash chromatography on silica gel eluting with dichloromethane/methanol/30% NH4OH 92:8:0.5 affording 416 mg of the title compound as pale yellow solid. The mixture was heated at reflux stirred for additional 6 hours After evaporation of the volatiles the residue was chromatographed on silica gel eluting with dichloromethane/methanol/triethylamine 90:10:0.1 affording 845 mg of N-[5-(3,5-difluoro-benzenesulfonyl)-1H-indazol-3-yl]-4-(2-dimethylamino-1-methyl-ethylamino)-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzamide that was dissolved in methanol (5 mL) triethylamine (2 mL) and stirred at 50° C. for 6 hours The mixture was then evaporated to dryness the residue purified by flash chromatography on silica gel eluting with dichloromethane/methanol/30% NH4OH 92:8:0.5 affording 416 mg of the title compound as pale yellow solid