2-methylbutanedioyl dichloride

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

Procedure: To a solution of 2,6-difluoroaniline (3.2 mL) in N,N-dimethylformamide (20 mL) was added methyl succinyl chloride (3.7 mL) at room temperature and the mixture was stirred for an hour. To the reaction mixture was added water and the mixture was extracted with ethyl acetate. The obtained organic layer was dried and concentrated. The obtained residue was purified by column chromatography on silica gel (hexane:ethyl acetate=7:3→3:2) to give the title compound (1.7 g) having the following physical data. the mixture was extracted with ethyl acetate The obtained organic layer was dried concentrated The obtained residue was purified by column chromatography on silica gel (hexane:ethyl acetate=7:3→3:2)

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

Procedure: To a solution of 2,6-difluoroaniline (3.2 mL) in N,N-dimethylformamide (20 mL) was added methyl succinyl chloride (3.7 mL) at room temperature and the mixture was stirred for an hour. To the reaction mixture was added water and the mixture was extracted with ethyl acetate. The obtained organic layer was dried and concentrated. The obtained residue was purified by column chromatography on silica gel (hexane:ethyl acetate=7:3→3:2) to give the title compound (1.7 g) having the following physical data. the mixture was extracted with ethyl acetate The obtained organic layer was dried concentrated The obtained residue was purified by column chromatography on silica gel (hexane:ethyl acetate=7:3→3:2)

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

Procedure: To a solution of 2,6-difluoroaniline (3.2 mL) in N,N-dimethylformamide (20 mL) was added methyl succinyl chloride (3.7 mL) at room temperature and the mixture was stirred for an hour. To the reaction mixture was added water and the mixture was extracted with ethyl acetate. The obtained organic layer was dried and concentrated. The obtained residue was purified by column chromatography on silica gel (hexane:ethyl acetate=7:3→3:2) to give the title compound (1.7 g) having the following physical data. the mixture was extracted with ethyl acetate The obtained organic layer was dried concentrated The obtained residue was purified by column chromatography on silica gel (hexane:ethyl acetate=7:3→3:2)

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

Procedure: To a stirred suspension of 271 (150 mg, 0.302 mmol) and DIPEA (123 μL, 0.707 mmol) in DMF (10 mL) was added methyl succinyl chloride (65 μl, 0.53 mmol). The reaction mixture was stirred at RT for 2.5 days. Water was added and the reaction mixture was extracted with DCM. The organic layer was successively washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by Biotage (SNAP 80 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV), to afford the title compound 272 (120 mg, 0.223 mmol, 63% yield) as an off-white solid. MS (m/z): 539.5 (M+H). the reaction mixture was extracted with DCM The organic layer was successively washed with brine dried over anhydrous sodium sulfate filtered concentrated The residue was purified by Biotage (SNAP 80 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV)