反应详情

A solution of (1-Methyl-3-phenyl-4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridin-6-yloxy)-acetic acid (350 mg, 0.996 mmol), DIC (189 mg, 1.494 mmol) and HOBt (175 mg, 1.295 mmol) in DMF (10 ml) was stirred at rt for 10 min. (S)-(−)-4-methoxy-α-methyl benzyl amine (166 mg, 1.096 mmol) was added to the reaction mixture at rt and stirring was continued for 12 h at rt. After completion of the reaction, the reaction mixture was poured into rapidly stirred ice-cold water to obtain the crude product as a solid. The solid was collected by filtration and dried under vacuum. The product was further purified by flash column chromatography [(eluent: EtOAc/hexane (1:3)] to yield the title compound as a white solid (305 mg, 63%). [1H-NMR (CDCl3, 300 MHz) δ 7.58-7.39 (m, 5H), 7.32-7.21 (m, 2H), 6.99 (s, 1H), 6.85 (d, 2H), 6.51 (d, 1H), 5.31-5.22 (m, 1H), 5.0 (s, 2H), 4.05 (s, 3H), 3.8 (s, 3H), 1.52 (d, 3H); HPLC RtB=5.933 min. (98%); LCMS RtA=1.785, [M+H]+=485.1; Mp=172-174° C.]

1. additionwas added to the reaction mixture at rt
2. customAfter completion of the reaction
3. additionthe reaction mixture was poured into rapidly stirred ice-cold water
4. customto obtain the crude product as a solid
5. filtrationThe solid was collected by filtration
6. customdried under vacuum
7. customThe product was further purified by flash column chromatography [(eluent