Hydrochloric Acid → HCID 66780490, compound

Participants

Reaction Steps

3-methoxypropionyl chloride (66.8 mg, 0.545 mmol) in 1,2-Dimethoxyethane (DME) (400 μl) was added to a solution of 4-{[(3-chloro-2-methylphenyl)methyl]amino}-2-(4-morpholinyl)-1,3-thiazole-5-carboxamide (100 mg, 0.273 mmol) in 1,2-Dimethoxyethane (DME) (1000 μl). The mixture was stirred at room temperature overnight, then quenched with methanol and concentrated. To the residue was added methanol (1 mL) followed by 6N NaOH (1 equiv.). The mixture was stirred at room temperature for 3 h, neutralized (pH ˜8) with 6N HCl, and concentrated. The residue was partitioned between dichloromethane and water. The organic layer was dried (sodium sulfate), filtered, and concentrated. The crude product was purified by reversed-phase HPLC and the fractions were neutralized with sat. aq. sodium bicarbonate. The combined fractions were concentrated to remove acetonitrile and the remaining water was extracted with dichloromethane. The organic layer was dried (sodium sulfate), filtered, and concentrated to provide 4-[(3-chloro-2-methylphenyl)methyl]-5-[2-(methyloxy)ethyl]-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one. (14 mg, 12%); LC/MS: MS (ES+) m/e 435 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.44 (s, 3H), 2.80 (t, J=6.7 Hz, 2H), 3.19 (s, 3H), 3.52 (m, 4H), 3.62-3.72 (m, 6H), 5.57 (s, 2H), 6.51 (d, J=7.6 Hz, 1H), 7.16 (m, 1H), 7.39 (d, J=7.8 Hz, 1H).

Provenance & Evidence