Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 2-[5-Chloro-2-(6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-3-ylamino)-pyrimidin-4-ylamino]-3-fluoro-N-methyl-benzamide

Participants

Reaction Steps

6,7,8,9-Tetrahydro-5-oxa-9-aza-benzocyclohepten-3-ylamine (0.115 g, 0.700 mmol), 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide (0.243 g, 0.770 mmol), and 10-Camphorsulfonic acid (251 mg, 1.08 mmol) in Isopropyl alcohol (4.00 mL) was irradiated in a CEM microwave (120° C., 30 min). The mixture was filtered and purified directly by HPLC to give enriched product, which was conc. and repurified. The fractions were concentrated and neutralized with MP-carbonate resin to afford 2-[5-Chloro-2-(6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-3-ylamino)-pyrimidin-4-ylamino]-3-fluoro-N-methyl-benzamide as a yellow foam (29 mg, 9%). LCMS: 443; 1H-NMR (CDCl3): 8.65 (s, 1H), 8.04 (m, 2H), 7.45 (m, 1H), 7.30 (m, 3H), 7.12 (s, 1H), 6.82 (m, 1H), 6.69 (m, 1H), 6.55 (d, 1H, J=8.4 Hz), 6.10 (q, 1H, J=4.0 Hz), 4.00 (t, 2H, J=5.2 Hz), 3.15 (t, 2H, J=5.5 Hz), 2.91 (d, 3H, J=4.8 Hz), 1.98 (m, 2H).

Provenance & Evidence