4-Methylmorpholine → 2-bromo-N-{4-methoxy-7-[methyl-(tetrahydro-pyran-4-yl)-amino]-benzothiazol-2-yl}-isonicotinamide

To a stirred solution of 103 mg (0.51 mmol) 2-bromo-isonicotinic acid in 3 ml THF were added 204 mg (0.53 mmol) HATU and 0.11 ml (1.02 mmol) N-methylmorpholine and stirring continued at 30° C. for 7 h. 75 mg (0.26 mmol) 4-methoxy-N7-methyl-N7-(tetrahydro-pyran-4-yl)-benzothiazole-2,7-diamine was then added and stirring continued at 40° C. for 16 h. The reaction mixture was then diluted with ethyl acetate and washed sequentially with saturated sodium bicarbonate solution and brine. The organic phase was dried over sodium sulfate and concentrated in vacuo. Flash chromatography (methanol/dichloromethane) followed by trituration in ether/pentane afforded 77 mg (63%) 2-bromo-N-{4-methoxy-7-[methyl-(tetrahydro-pyran-4-yl)-amino]-benzothiazol-2-yl}-isonicotinamide as a white crystalline solid. ES-MS m/e (%): 479 (M{81Br}+H+, 100), 477 (M{79Br}+H+, 95).

1. stirringstirring
2. waitcontinued at 40° C. for 16 h
3. washwashed sequentially with saturated sodium bicarbonate solution and brine
4. dry with materialThe organic phase was dried over sodium sulfate
5. concentrationconcentrated in vacuo

ORD record

ord-39592673635c4012b2c39da7b52f706e

Source dataset

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06713499B2