Potassium tert-butoxide → HCID 56971111, compound

Participants

Reaction Steps

A mixture of 3-(dimethylamino)-1-(2-methyl-3-f uranyl)-2-(2-methyl-4-pyridinyl)-2-propen-1-one (1352 mg, 5 mmol) and 2,6-dimethyl-4-morpholinecarboximidamide hydrochloride (1453 mg, 7.50 mmol) (ca. 2.3:1 mixture of cis:trans isomers) in ethanol (10 ml) was stirred at room temperature. Potassium tert-butoxide (1122 mg, 10.00 mmol) was added and the mixture was heated at reflux for 3 hours. After cooling to room temperature the solvent was evaporated and the residue was diluted with water and extracted with ethyl acetate. The organic extracts were combined, washed with water and brine, dried and evaporated. The residue was purified by silica gel chromatography eluting with 50% ethyl acetate in isohexane to give cis-2,6-dimethyl-4-[4-(2-methyl-3-furanyl)-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]morpholine as an oil (200 mg). The cross-over fractions from the column (˜800 mg) were purified by mass-directed automated HPLC to give additional cis-2,6-dimethyl-4-[4-(2-methyl-3-furanyl)-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]morpholine (200 mg) and trans-2,6-dimethyl-4-[4-(2-methyl-3-furanyl)-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]morpholine (49 mg). A solution of cis-2,6-dimethyl-4-[4-(2-methyl-3-furanyl)-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]morpholine (200 mg, 0.55 mmol) was dissolved in dichloromethane (2 ml) and hydrogen chloride (1M in ether, 0.6 ml) was added. The solvent was evaporated and the residue was evaporated with ether (×2) and then triturated with ether. The solid was collected, washed with ether and dried to give the title compound (178 mg). LC/MS [M+H]+=365. 1H NMR (400 MHz, d6-DMSO): δ 8.61 (1H, d), 8.56 (1H, s), 7.82 (1H, b), 7.58-7.53 (1H, m), 7.52 (1H, d), 6.04 (1H, d), 4.65-4.58 (2H, m), 3.64-3.55 (2H, m), 2.72-2.63 (2H, m), 2.66 (3H, s), 2.36 (3H, s), 1.18 (6H, d).

Provenance & Evidence