Sodium Carbonate → cis-4-[4-(6-Fluoro-4-methyl-3-pyridinyl)-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]-2,6-dimethylmorpholine hydrochloride

Participants

Reaction Conditions

Reaction Steps

Sodium carbonate (166 mg, 1.568 mmol) in water (2 ml), bis(triphenylphosphine)palladium(II)chloride (11.01 mg, 0.016 mmol) and (6-fluoro-4-methyl-3-pyridinyl)boronic acid (72.9 mg, 0.471 mmol) were added to a solution of cis-4-[4-chloro-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]-2,6-dimethylmorpholine (100 mg, 0.314 mmol) in 1,2-dimethoxyethane (DME) (3 ml). The reaction mixture was heated to 80° C. for 1 hour. After cooling to room temperature the reaction mixture was partitioned between ethyl acetate (20 mL) and water (20 mL). The organic layer was passed through a hydrophobic frit to remove traces of water and then evaporated to dryness to give a brown gum. The residue was subject to MDAP purification in 1 mL of 50:50 DMSO:MeOH. Clean fractions were combined and evaporated to dryness to give a white solid. The free base was generated by partitioning between sodium bicarbonate and dichloromethane. The organic layer was dried by passing through a hydrophobic frit and then the HCl salt was generated by addition of 1M HCl in diethylether (132 ul). The solvent was evaporated and the residue was co-evaporated with ether. The residue was triturated with ether and the resulting solid was collected and dried at 40° C. under vacuum for 1 hour to give the title compound as a cream solid (9 mg, 6%). LC/MS [M+H]+=394. 1H NMR (400 MHz, d6-DMSO): δ 8.74 (1H, s), 8.49 (1H, d), 7.96 (1H, s), 7.65 (1H, s), 7.20 (1H, d), 7.17 (1H, s), 4.67-4.50 (2H, m), 3.70-3.44 (2H, m, hidden under water peak), 2.73-2.63 (2H, m), 2.59 (3H, s), 2.20 (3H, s), 1.17 (6H, d).

Provenance & Evidence