6,6-difluoro-1,4-diazepane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of methanesulfonic anhydride (114 mg, 3.2 equiv.) in DCM (0.6 mL) was added to a solution of {4-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-yl}-methanol (78 mg, 2 mmole) in dry DCM (1.4 mL) at 0° C. under nitrogen followed by triethylamine (0.140 mL, 5 equiv.). After stirring at 0° C. for 1 hr, 6,6-difluoro-[1,4]diazepane (82 mg, 3 equiv.) and 1,2 dichloroethane (2 mL) were added. The reaction mixture was transferred to a microwave reactor (Personal Chemistry's Smith Creator) and irradiated at 65° C. for 50 min. Removal of the solvent followed by preparative HPLC afforded the title compound as a solid (29 mg, 29%). MS: 507 (M+H+); HPLC Ret Time: 1.47 min (YMC Xterra ODS S7 3.0×50 mm column, 2 min gradient, 5 ml/min). The reaction mixture was transferred to a microwave reactor (Personal Chemistry's Smith Creator) and irradiated at 65° C. for 50 min Removal of the solvent

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of methanesulfonic anhydride (114 mg, 3.2 equiv.) in DCM (0.6 mL) was added to a solution of {4-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-yl}-methanol (78 mg, 2 mmole) in dry DCM (1.4 mL) at 0° C. under nitrogen followed by triethylamine (0.140 mL, 5 equiv.). After stirring at 0° C. for 1 hr, 6,6-difluoro-[1,4]diazepane (82 mg, 3 equiv.) and 1,2 dichloroethane (2 mL) were added. The reaction mixture was transferred to a microwave reactor (Personal Chemistry's Smith Creator) and irradiated at 65° C. for 50 min. Removal of the solvent followed by preparative HPLC afforded the title compound as a solid (29 mg, 29%). MS: 507 (M+H+); HPLC Ret Time: 1.47 min (YMC Xterra ODS S7 3.0×50 mm column, 2 min gradient, 5 ml/min). The reaction mixture was transferred to a microwave reactor (Personal Chemistry's Smith Creator) and irradiated at 65° C. for 50 min Removal of the solvent

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of methanesulfonic anhydride (114 mg, 3.2 equiv.) in DCM (0.6 mL) was added to a solution of {4-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-yl}-methanol (78 mg, 2 mmole) in dry DCM (1.4 mL) at 0° C. under nitrogen followed by triethylamine (0.140 mL, 5 equiv.). After stirring at 0° C. for 1 hr, 6,6-difluoro-[1,4]diazepane (82 mg, 3 equiv.) and 1,2 dichloroethane (2 mL) were added. The reaction mixture was transferred to a microwave reactor (Personal Chemistry's Smith Creator) and irradiated at 65° C. for 50 min. Removal of the solvent followed by preparative HPLC afforded the title compound as a solid (29 mg, 29%). MS: 507 (M+H+); HPLC Ret Time: 1.47 min (YMC Xterra ODS S7 3.0×50 mm column, 2 min gradient, 5 ml/min). The reaction mixture was transferred to a microwave reactor (Personal Chemistry's Smith Creator) and irradiated at 65° C. for 50 min Removal of the solvent