7-Amino-3-ethyl-8-methoxy-1,3,4,5-tetrahydro-benzo[d]azepin-2-one → N-{(1R,2R)-2-[5-chloro-2-(3-ethyl-8-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide

Participants

Reaction Steps

Following a procedure similar to 247b, 7-amino-3-ethyl-8-methoxy-1,3,4,5-tetrahydro-benzo[d]azepin-2-one (46 mg, 0.18 mmol) was reacted with N-[(1R,2R)-2-(2,5-dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (60.60 mg, 0.18 mmol), except that the product precipitated from the reaction mixture in the hydrochloride salt form, was collected by filtration, and then free-based by treatment of a solution of the salt in dichloromethane with aqueous saturated NaHCO3. The organic solution was dried (MgSO4), and concentrated to afford N-{(1R,2R)-2-[5-chloro-2-(3-ethyl-8-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide (35 mg, 36%) as a white solid. MP: 139-150° C.; 1H-NMR (CDCl3) δ 8.00 (s, 1H), 7.95 (s, 1H), 7.33 (s, 1H), 6.65 (s, 1H), 5.25-5.40 (m, 2H), 3.95 (m, 1H), 3.88 (s, 3H), 3.84 (s, 2H), 3.73 (t, J=5.8 Hz, 2H), 3.48 (q, J=7.1 Hz, 2H), 3.25 (m, 1H), 3.12 (t, J=5.6 Hz, 2H), 2.80 (s, 3H), 2.20 (m, 2H), 1.80 (br s, 2H), 1.40 (s, 4H), 1.17 (t, J=7.1 Hz, 3H); LC/MS (ESI+): 537.31 (M+H).

Provenance & Evidence