Sodium Carbonate → 1-((2-(1H-indol-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,N-dimethylpiperidin-4-amine

Participants

Reaction Conditions

Reaction Steps

A microwave vessel was charged with [1-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-dimethyl-amine (0.500 g, 1.26 mmol), 1-BOC-indole-3-yl-boronic acid (363 mg, 1.39 mmol), 1 N sodium carbonate solution (3 mL), acetonitrile (9 mL) and Pd(dppf)Cl2 (103 mg. 0.126 mmol), then the mixture was degassed, sealed, and heated at 140° C. under microwave irradiation for 20 min. The reaction mixture was diluted with dichloromethane (100 mL) and 1 N sodium carbonate solution (10 mL) then the phases were separated. The organic phase was washed with saturated aqueous sodium bicarbonate solution (15 mL) then dried (MgSO4) and concentrated in vacuo. Purification by chromatography (silica, 0 to 15% of a 9.5:0.5 MeOH:NH4OH solution in dichloromethane) followed by trituration with hot ethanol afforded 101 (161 mg, 27%) as a cream powder. MS m/e 477 [M+H]+. 1H NMR (400 MHz, CHCl3-d) δ ppm 1.53-1.68 (m, 2H) 1.75 (br. s., 1H) 1.83 (d, J=11.6 Hz, 2H) 2.05-2.22 (m, 3H) 2.30 (s, 6H) 3.04 (d, J=12.1 Hz, 2H) 3.81 (s, 2H) 3.88-3.99 (m, 4H) 4.01-4.13 (m, 4H) 7.21-7.32 (m, 2H) 7.37-7.45 (m, 1H) 8.14 (d, J=2.5 Hz, 1H) 8.64-8.70 (m, 1H) 8.76 (br. s., 1H)

Provenance & Evidence