Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → cis-2-[5-Chloro-2-(3-dimethylcarbamoylmethyl-8-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclopentanecarboxylic acid methylamide

Participants

Reaction Conditions

Reaction Steps

cis-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclopentanecarboxylic acid methylamide (46 mg, 0.160 mmol), 2-(7-amino-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N,N-dimethyl-acetamide (44 mg, 0.160 mmol) and camphorsulfonic acid (56 mg, 0.240 mmol) were combined in 3 mL isopropanol and heated at 120° C. in microwave for a total of 90 min. The reaction was concentrated to be taken up in dichloromethane and washed with saturated sodium bicarbonate solution (2×30 mL). The organic layer was dried over MgSO4 and filtered. The filtrate was chromatographed on a 4 g amine capped ISCO flash column from 0-100% ethyl acetate in hexanes. The product was collected as a foam after concentrating to afford 43 mg (51%) of a white foam. Compound 5: mp 240° C.; MS (ES+ calculated—529; found—530 M+H). 1H NMR (400 MHz, CDCl3) δ 8.22 (s, 1H), 7.89 (s, 1H), 7.40 (s, 1H), 6.65 (s, 1H), 6.14 (d, J=7 Hz, 1H), 5.57 (br s, 1H), 4.61 (t, J=7 Hz, 1H), 3.88 (s, 3H), 3.29 (s, 2H), 3.15 (s, 3H), 2.99 (s, 3H), 2.89 (s, 4H), 2.71 (d, J=4 Hz, 6H), 2.17 (m, 1H), 2.08 (m, 1H), 1.98 (br s, 2H), 1.65 (m, 1H) ppm.

Provenance & Evidence