Potassium Carbonate → 6-(3-(Hydroxyethoxy)thiophen-2-YL)-1-((tetrahydro-2H-pyran-4-YL)methyl)-1H-imidazo[4,5-B]pyrazin-2(3H)-one

Participants

Reaction Conditions

Reaction Steps

6-(3-(Hydroxymethyl)thiophen-2-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one. To a solution of 3-formylthiophen-2-ylboronic acid (0.156 g, 1 mmol) in methanol (2 mL) was added sodium tetrahydroborate (0.378 g, 10.00 mmol). The mixture was stirred at 25° C. for 10 min. 6-Bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (See Example 101.B) (0.157 g, 0.500 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane (0.041 g, 0.050 mmol), potassium carbonate (0.138 g, 1.000 mmol), 1,4-dioxane (2 mL), and water (6.00 ml) were then added. The reaction mixture was heated in a Biotage Emrys Optimizer microwave reactor at 140° C. for 30 min. The reaction mixture was then extracted with ethyl acetate (3×25 mL) and washed with aqueous sodium bicarbonate (3×25 ml). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated. The crude material was subjected to silica gel chromatography (100% ethyl acetate). Concentration of the desired fractions afforded the title compound (0.070 g, 40.4%) as an off white solid. 1H NMR (400 MHz, DMSO-d6) δ 12.09 (s, 1H), 8.20 (s, 1H), 7.54 (d, J=5.2, 1H), 7.21 (d, J=5.2, 1H), 5.30 (t, J=5.4, 1H), 4.67 (d, J=5.6, 2H), 3.85-3.82 (m, 2H), 3.73 (d, J=7.2, 2H), 3.27-3.22 (m, 2H), 2.15-2.07 (m, 1H), 1.57-1.54 (m, 2H), 1.34-1.23 (m, 2H); MS (ESI) m/z 347.1 [M+1]+.

Provenance & Evidence