Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 2-[5-Chloro-2-(1-ethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-ylamino)pyrimidin-4-ylamino]-3-fluoro-N-methyl-benzamide

Participants

Reaction Conditions

Reaction Steps

A microwave vessel was charged with 2-(2,5-dichloro-pyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide (57.5 mg, 0.182 mmol), 8-amino-1-ethyl-1,3,4,5-tetrahydro-1-benzazepin-2-one (44.7 mg, 0.219 mmol), 10-camphorsulfonic acid (5.0 mg, 0.022 mmol) and isopropyl alcohol (2 mL) and heated at 120° C. for 60 minutes in a microwave reactor (sealed vessel). The reaction mixture was quenched with a slurry of saturated, aqueous NaHCO3 and stirred for 2 h. The resulting precipitate was filtered, washed with water (5×2 mL), ether (2×2 mL) and dried under vacuum to afford product 65.7 mg, 69%) as a tan solid that had the following properties: mp: 228-235° C.; LC/MS (ESI+): 483 (M+H); 1H-NMR (DMSO-d6, 400 MHz): δ 9.38-9.35 (m, 2H), 8.53 (m, 1H), 8.19 (s, 1H), 7.48-7.45 (m, 2H), 7.36-7.26 (m, 3H), 6.98 (d, J=8.3, 1H), 3.55 (br s, 2H), 2.74 (d, J=4.1, 3H), 2.50 (m, 2H), 2.10-1.85 (m, 4H), 0.93 (t, J=7.0, 3H).

Provenance & Evidence