Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 8-{5-Chloro-4-[2-(pyrrolidine-1-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-1,3,4,5-tetrahydro-benzo[b]azepin-2-one

Participants

Reaction Steps

8-Amino-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (0.037 g, 0.21 mmol), (2,5-Dichloro-pyrimidin-4-yl)-[2-(pyrrolidine-1-sulfonyl)-phenyl]-amine (0.072 g, 0.19 mmol) and 10-Camphorsulfonic acid (0.0045 g, 0.019 mmol) in Isopropyl alcohol (1 mL) was irradiated in a CEM microwave (120° C., 30 min). One mL Sodium bicarbonate and 1 mL water were added to the reaction mixture, which was then filtered and the resulting ppt was washed first with water then three times with 1 mL of Isopropyl alcohol. The solid was then purified by silica gel chromatography (ISCO, 0-100% EtOAc) to afford 8-{5-Chloro-4-[2-(pyrrolidine-1-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-1,3,4,5-tetrahydro-benzo[b]azepin-2-one as a white powder (59 mg, 60%). MP 249-251° C.; LCMS: 513 (M+H); 1H-NMR (DMSO): 9.56 (s, 1H), 9.45 (s, 1H), 9.41 (s, 1H), 8.61 (s, 1H), 8.29 (s, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.67 (dd, J=8.0 Hz, 1H), 7.34 (d, J=8.0 Hz, 1H), 7.31 (s, 1H), 7.27 (s, 1H), 7.09 (d, J=8.0 Hz, 1H), 3.14 (t, J=4.0 Hz, 4H), 2.62 (t, J=8.0 Hz, 2H), 2.15 (t, J=8.0 Hz, 2H), 2.07 (m, 2H), 1.68 (m, 4H).

Provenance & Evidence