反应详情

To a solution of isonicotinic acid 4 (150 mg, 0.744 mmol), 4-benzyloxy-3,5-dimethyl-benzoic acid hydrazide (200 mg, 0.740 mmol) and DIPEA (302 mg, 2.34 mmol) in DCM (15 mL) PyBOP (420 mg, 0.807 mmol) is added portionwise at 0° C. The mixture is stirred at 0° C. for 3 h before pyridine (295 mg, 3.73 mmol) followed by trifluoromethanosulfonic acid anhydride (214 mg, 1.17 mmol) is added. The mixture is stirred at rt for 15 h before another portion of pyridine (295 mg, 3.73 mmol) and trifluoromethanosulfonic acid anhydride (214 mg, 1.17 mmol) is added. After stirring for 2 h yet another portion of pyridine (295 mg, 3.73 mmol) and trifluoromethanosulfonic acid anhydride (214 mg, 1.17 mmol) is added and stirring is continued for 2 h. Dimethylaminopropylamine (0.25 mL) is added and the mixture is stirred for 30 min before it is diluted with ether (100 mL), washed with 1 M aq. NaH2PO4 solution (2×30 mL) and sat. aq. Na2CO3 solution. The washings are extracted back with EA (2×75 mL). The combined org. extracts are dried over MgSO4, filtered and evaporated to give crude 4-[5-(4-benzyloxy-3,5-dimethyl-phenyl)-[1,3,4]oxadiazol-2-yl]-2-ethyl-6-methyl-pyridine; LC-MS: tR=1.12 min; [M+1]+=400.22. To a solution of this material in formic acid (0.125 mL), MeOH (5 mL) and THF (10 mL), Pd/C (50 mg, 10% Pd) is added and the mixture is stirred at rt under 1 bar of H2 for 15 h. The catalyst is removed by filtration and the solvent of the filtrate is evaporated. The residue is dissolved in EA (100 mL), washed with sat. aq. NaHCO3 solution, dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with EA to give 4-[5-(2-ethyl-6-methyl-pyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-2,6-dimethyl-phenol (209 mg) as a beige foam; LC-MS: tR=0.74 min; [M+1]+=310.11.

1. additionis added
2. additionis added
3. additionis added
4. stirringthe mixture is stirred for 30 min before it
5. washwashed with 1 M aq. NaH2PO4 solution (2×30 mL) and sat. aq. Na2CO3 solution
6. extractionThe washings are extracted back with EA (2×75 mL)
7. dry with materialextracts are dried over MgSO4
8. filtrationfiltered
9. customevaporated
10. customto give crude 4-[5-(4-benzyloxy-3,5-dimethyl-phenyl)-[1,3,4]oxadiazol-2-yl]-2-ethyl-6-methyl-pyridine
11. stirringthe mixture is stirred at rt under 1 bar of H2 for 15 h
12. customThe catalyst is removed by filtration
13. customthe solvent of the filtrate is evaporated
14. dissolutionThe residue is dissolved in EA (100 mL)
15. washwashed with sat. aq. NaHCO3 solution
16. dry with materialdried over MgSO4
17. filtrationfiltered
18. concentrationconcentrated
19. customThe crude product is purified by CC on silica gel eluting with EA