tert-butyl 2-(bis(tert-butoxycarbonyl)amino)-5-(trimethylstannyl)-1H-benzo[d]imidazole-1-carboxylate → HCID 178508158, compound

Participants

Reaction Steps

6-(2-Amino-1H-benzo[d]imidazol-5-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one dihydrochloride. A solution of tert-butyl 2-(bis(tert-butoxycarbonyl)amino)-5-(trimethylstannyl)-1H-benzo[d]imidazole-1-carboxylate (120 mg, 0.20 mmol), 6-Bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (See Example 101.B) (63 mg, 0.2 mmol), and dichlorobis(triphenylphosphine)palladium(II) (14 mg, 0.02 mmol) in DMF (5 mL) was reacted for 1.5 h at 90° C. The product was purified by reverse-phase semi-preparatory HPLC (20-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The desired fractions were concentrated, and treated with 4N hydrochloric acid in diethyl ether (few drops), sonicated and concentrated. This procedure was repeated twice more to provide the title compound (10.2 mg, 12.7% yield). 1H NMR (400 MHz, DMSO-d6) 12.54 (d, J=11.2, 2H), 12.09 (s, 1H), 8.53 (s, 1H), 8.49 (s, 1H), 7.97 (s, 1H), 7.90 (d, J=8.4, 1H), 7.44 (d, J=8.4, 1H), 3.84 (d, J=10.8, 2H), 3.79 (d, J=10.8, 2H), 3.26 (t, J=10.8, 2H), 2.13 (m, 1H), 1.58 (m, 2H), 1.35-1.23 (m, 3H); MS (ESI) m/z 366.1 [M+1]+.

Provenance & Evidence