7-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine → 7-chloro-6-{[5-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridin-2-ylmethyl]-amino}-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Participants

Reaction Steps

Use a method similar to the General Procedure 1-2 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (316 mg, 0.74 mmol) with 2-aminomethyl-5-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridine (290 mg, 1.11 mmol) in toluene (8 mL). Filter the crude mixture over Celite®, followed by activated charcoal and wash with dichloromethane. Concentrate the filtrate in vacuo and purify the crude mixture by chromatography on silica gel (12 g) eluting with hexane/(EtOAc with 1% methanol) (20:1 to 3:2 gradient) to obtain 7-chloro-6-{[5-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridin-2-ylmethyl]-amino}-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (120 mg, 30%). MS (ES+) m/z: 536.3 (M+H)+.

Provenance & Evidence