Reaction Steps
9-Amino-7-fluoro-3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-one (59 mg, 0.30 mmol), 10-Camphorsulfonic acid (11 mg, 0.047 mmol) and N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (0.104 g, 0.306 mmol) in 2-Methoxyethanol (5 mL) were heated at 110° C. under an atmosphere of Nitrogen for 2 days. The mixture was cooled to r.t., neutralized with 100 mg MP-Carbonate and conc. in vacuo. The residue was partially taken up in DCM/MeOH, and the remainder was powdered onto Celite, then chromatographed (2×12 g silica gel, ISCO, 0-100% EtOAc:hexane, then 10% MeOH) to afford N-{(1R,2R)-2-[5-Chloro-2-(7-fluoro-5-oxo-2,3,4,5-tetrahydro-benzo[f][1,4]oxazepin-9-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide as a beige solid (69 mg, 46%). MP=177-181° C.; LCMS: 499 (M+H); 1H-NMR (CDCl3): 8.27 (dd, 1H, J=2.6, 10.9 Hz), 7.98 (1H, s), 7.62 (s, 1H), 7.03 (dd, 1H, J=2.9, 8.6 Hz), 6.95 (m, 1H), 6.85 (m, 1H), 6.02 (d, 1H, J=7.0 Hz), 4.21 (m, 1H), 4.15 (m, 1H), 3.82 (m, 1H), 3.32 (m, 3H), 2.98 (s, 3H), 2.33 (m, 1H), 2.18 (m, 1H), 1.87 (m, 1H), 1.78 (m, 1H), 1.64 (m, 1H), 1.41 (m, 2H), 1.22 (m, 1H).
