3-Carboxyphenylboronic acid → (6-Biphenyl-4-yl-2-methoxy-pyrimidin-4-yl)-[2-(3,4-dimethoxy-phenyl)-ethyl]-amine

Participants

Reaction Steps

By proceeding in a similar manner as above in Example 35(a) but (i) substituting (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(3,4-dimethoxy-phenyl)-ethyl]-amine [100 mg, Intermediate (42)] for (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxy-phenyl)-ethyl]-amine, and (ii) substituting 4-Biphenylboronic acid (122 mg) for 3-carboxyphenyl boronic acid, and (iii) subjecting the crude reaction product to flash column chromatography on silica (10 g) eluting with 20 to 60% EtOAc in heptane gradient, there is prepared (6-biphenyl-4-yl-2-methoxy-pyrimidin-4-yl)-[2-(3,4-dimethoxy-phenyl)-ethyl]-amine [79.7 mg, 58.6%, Example 35(e)]. LCMS: RT=3.05 minutes, MS: 442 (M+H). 1H NMR (300 MHz, CDCl3), δ 8.36 (1H, d, J=0.027 Hz), 8.09 (2H, d, J=0.027 Hz), 7.84 (1H, d, J=0.027 Hz), 7.78 (1H, d, J=0.027 Hz), 7.68 (9H, m), 7.45 (4H, m), 6.84 (1H, t, J=0.027 Hz), 6.79 (2H, m), 6.44 (1H, s), 4.93 (1H, s), 4.77 (1H, s), 4.07 (3H, s), 3.9 (6H, s), 3.72 (2H, m), 2.94 (2H, t, J=0.022 Hz). IC50=369 nM

Provenance & Evidence