反应详情

To a solution of methyl 1-{5-[({5-[(3,4-difluorophenyl)amino]-1,3,4-oxadiazol-2-yl}carbonyl)amino]pyridin-2-yl}-4-methylpiperidine-4-carboxylate (Example 631; 282 mg, 0.60 mmol) in MeOH (10 mL) was added a 2M solution of NaOH (1.5 mL). The resulting yellow solution was allowed to stir at ambient temperature overnight. The reaction mixture was then heated to 50° C. for 8 hours and allowed to stir at ambient temperature overnight. The volatile organics were removed by evaporation, the aqueous residue was washed with ether (50 mL) and aqueous phase adjusted to pH ˜1 with 2M HCl. The resultant suspension was filtered and dried under vacuum at ambient temperature to give the title compound (230 mg, 0.502 mmol, 84%); 1H NMR δ 1.21 (s, 3H), 1.47-1.54 (m, 2H), 2.03-2.08 (m, 2H), 3.29-3.36 (m, 2H), 3.95-4.00 (m, 2H), 7.30 (d, 1H), 7.37-7.41 (m, 1H), 7.48 (q, 1H), 7.69-7.75 (m, 1H), 8.15 (d, 1H), 8.54 (s, 1H), 11.25 (s, 1H), 11.37 (s, 1H); CO2H not seen; MS m/e MH+ 459.

1. temperatureThe reaction mixture was then heated to 50° C. for 8 hours
2. stirringto stir at ambient temperature overnight
3. customThe volatile organics were removed by evaporation
4. washthe aqueous residue was washed with ether (50 mL) and aqueous phase
5. filtrationThe resultant suspension was filtered
6. customdried under vacuum at ambient temperature