D-Camphorsulfonic Acid → 3-Chloro-2-[5-chloro-2-(1-ethyl-5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide

Participants

Reaction Steps

Combined 3-Chloro-2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (91 mg, 0.275 mmol), 7-Amino-1-ethyl-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (64 mg, 0.275 mmol), DL-10-Camphorsulfonic acid (82 mg, 0.353 mmol) and 2-methoxyethanol (3 mL). Heated reaction to 120° C. for 2.5 hours. Evaporated off solvent, dissolved residue in methylene chloride and washed with saturated sodium bicarbonate solution, then brine. Dried with magnesium sulfate, filtered and purified with normal phase chromatography using basic alumina silica gel to yield a yellow solid, 3-Chloro-2-[5-chloro-2-(1-ethyl-5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide (15 mg, 10%). LCMS: m/z=527.54 (M+H+), 1H NMR (400 MHz, CDCl3) δ 8.12 (d, 1H, J=1.0 Hz), 8.02 (br s, 1H), 7.59 (d, 1H, J=8.1 Hz), 7.51 (m, 2H), 7.28 (m, 1H), 7.21 (m, 2H), 7.02 (d, 1H, J=8.6 Hz), 6.25 (d, 1H, J=4.6 Hz), 4.13 (m, 2H), 3.76 (m, 2H), 2.82 (d, 3H, J=4.3 Hz), 2.22 (m, 2H), 1.27 (m, 9H).

Provenance & Evidence