反应详情

To a solution of 6-isobutyl-4-methoxy-pyridine-2-carboxylic acid (270 mg, 1.10 mmol), 4-benzyloxy-3,5-dimethyl-benzoic acid hydrazide (327 mg, 1.21 mmol) and DIPEA (455 mg, 3.52 mmol) in DCM (15 mL), PyBOP (858 mg, 1.65 mmol) is added at 0° C. The mixture is stirred for 30 min at rt, the reaction is diluted with diethyl ether and washed with 1 N aq. NaOH solution followed by 1 M aq. NaH2PO4 solution. The org. extract is dried over Na2SO4, filtered and concentrated to give the crude hydrazide intermediate; LC-MS: tR=1.00 min, [M+H]+=462.23. This material (1.13 g) is dissolved in DCM (15 mL) and pyridine (1 mL) and the mixture is cooled to 0° C. before trifluoromethanesulfonic anhydride (1.38 g, 4.89 mmol) is added dropwise. The mixture is warmed to rt and stirring is continued for 16 h. The reaction is quenched by adding 3-dimethylamino-1-propylamine (50 mg, 0.49 mmol). The mixture is washed twice with 1 N aq. NaH2PO4 solution followed by water, dried over Na2SO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 4:1 to give 2-[5-(4-benzyloxy-3,5-dimethyl-phenyl)-[1,3,4]oxadiazol-2-yl]-6-isobutyl-4-methoxy-pyridine (414 mg) as a yellow oil; LC-MS: tR=1.15 min, [M+H]+=444.21.

1. washwashed with 1 N aq. NaOH solution
2. extractionextract
3. dry with materialis dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customto give the crude hydrazide intermediate
7. additionis added dropwise
8. temperatureThe mixture is warmed to rt
9. stirringstirring
10. waitis continued for 16 h
11. customThe reaction is quenched
12. washThe mixture is washed twice with 1 N aq. NaH2PO4 solution
13. dry with materialdried over Na2SO4
14. filtrationfiltered
15. concentrationconcentrated
16. customThe crude product is purified by CC on silica gel eluting with heptane:EA 4:1