Methyl iodide → HCID 86686141, compound

Participants

Reaction Conditions

Reaction Steps

To a stirring solution of ethyl 2-(6-(t-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-hydroxy-2,5-dihydrothiazole-5-carboxylate (350 mg, 0.7 mmol) in DMF (4 mL) was added methyl iodide (200 μL, 3.3 mmol) and sodium hydride (60% dispersion in mineral oil, 40 mg, 1 mmol). The reaction was stirred at rt for 1 h and at 40° C. for 45 min. The reaction was then concentrated and quenched with water (5 mL), poured into ethyl acetate (150 mL), and washed with 0.1M HCl (50 mL, aq) and brine (50 mL). The organic layer was separated, dried over Na2SO4, filtered, concentrated and purified by silica gel column chromatography (EtOAC/hexanes) to afford 205 mg of ethyl 2-(6-(tert-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-methoxy-2,5-dihydrothiazole-5-carboxylate. This compound was dissolved in methanol (4 mL) and 1M KOH (aq, 2 mL). The reaction mixture was heated to 75° C. and stirred for 45 min. The reaction was cooled and the pH was adjusted to 4 using 1M HCl. The reaction was then poured into ethyl acetate (50 mL), washed with brine (15 mL), dried over Na2SO4, filtered, and concentrated to give 175 mg of 2-(6-(t-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-methoxy-2,5-dihydrothiazole-5-carboxylic acid as a white foam.

Provenance & Evidence