Sodium Hydroxide → HCID 24995282, compound

Participants

Reaction Conditions

Reaction Steps

Ethyl 5-(2-(3-(1-(tert-butoxycarbonyl)piperidin-4-yl)-1,2,4-thiadiazol-5-ylamino)-5-bromopyridin-4-yloxy)-4,6-dimethylnicotinate (0.50 g, 0.79 mmol) was dissolved in EtOH (10 mL). NaOH (1N in H2O, 2.0 ml, 2.0 mmol) was added. The reaction stirred at 60° C. for 3 hours. The solution was cooled and concentrated to give the hydrolyzed product as a yellow salt. This residue was re-dissolved in DMF (2 mL). N1,N1-dimethylethane-1,2-diamine (0.31 ml, 2.8 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.45 g, 2.4 mmol) and HOBT-H2O (0.36 g, 2.4 mmol) were added. The reaction stirred at 50° C. for 2 hours. The solution was cooled, diluted with water (15 mL), extracted with EtOAc, dried, and concentrated. Flash chromatography (DCM-15% MeOH/DCM/0.1-1% NH4OH) gave tert-butyl 4-(5-(4-(5-((2-(dimethylamino)ethyl)carbamoyl)-2,4-dimethylpyridin-3-yloxy)-5-bromopyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidine-1-carboxylate (0.30 g, 56%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 1.45 (s, 9H), 1.70-1.77 (m, 2H), 1.95-1.99 (m, 2H), 2.25 (s, 3H), 2.29 (s, 6H), 2.39 (s, 3H), 2.56-2.62 (m, 2H), 2.85-2.89 (m 3H), 3.52-2.64 (m, 2H), 4.08-4.15 (m, 2H), 5.95 (s, 1H), 7.07 (s, 1H), 8.30 (s, 1H), 8.53 (s, 1H), 10.15 (s, 1H).

Provenance & Evidence