6-Bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one → HCID 178518663, compound

Participants

Reaction Steps

6-(1H-Benzo[d]imidazol-5-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazol-[4,5-b]pyrazin-2(3H)-one hydrochloride. tert-Butyl 5-(trimethylstannyl)-1H-benzo[d]imidazole-2-carboxylate (640 mg, 1.7 mmol), 6-bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (See Example 101.B) (420 mg, 1.3 mmol), dichlorobis(triphenylphosphine)palladium(II) (90 mg, 0.13 mmol) in DMF (25 mL) were reacted for 1.5 h at 90° C. The product was purified by reverse-phase semi-preparatory HPLC (30-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The desired fractions were concentrated, treated with 4N hydrochloric acid in diethyl ether (few drops), and sonicated. This procedure was repeated twice more to provide 6-(1H-benzo[d]imidazol-5-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (48 mg, 10% yield) as the hydrochloride salt. 1H NMR (400 MHz, DMSO-d6) 12.07 (s, 1H), 8.55 (s, 1H), 8.52 (s, 1H), 8.33 (s, 1H), 8.06 (dd, J=8.0, 1.6, 1H), 7.80 (d, J=8.8, 1H), 3.81 (m, 2H), 3.80 (d, J=7.2, 2H), 3.27 (d, J=11.6, 2H), 2.14 (m, 1H), 1.59 (m, 2H), 1.33 (m, 2H); MS (ESI) m/z 351.2 [M+1]+.

Provenance & Evidence