反应详情

Triphenylphosphine (0.694 g, 2.65 mmol), tetrahydrofuran (2.12 mL), 2-piperidylethanol (0.352 mL, 2.65 mmol) and diethylazodicarboxylate (0.418 mL, 2.65 mmol) were added to 3-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)]-1H-indazol-3-yl}phenol (0.400 g, 0.662 mmol). The mixture was stirred at ambient temperature for 23 h and poured into aqueous 6 N hydrochloric acid (30 mL). After stirring at ambient temperature for 4 h, the mixture was extracted with ether (3×). The aqueous fraction was added to aqueous 6 N sodium hydroxide (30 mL) and the pH adjusted to 11. The solution was extracted with ethyl acetate (3×) and the organic fractions were combined and dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography on silica pretreated with 2% triethylamine/ethyl acetate elution followed by 0–20% methanol/ethyl acetate. The desired fractions were concentrated, dissolved in ethyl acetate, washed with aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and evaporated which gave the title compound (0.124 g, 48% yield). 1H NMR (CD3OD) δ 8.72 (m, 1H), 8.34 (s, 1H), 8.10 (dd, 1H), 7.67 (dd, 1H), 7.62 (dt, 1H), 7.58 (m, 1H), 7.47 (t, 1H), 7.04 (m, 1H), 4.27 (t, 2H), 2.89 (t, 2H), 2.63 (m, 4H), 1.68 (m, 4H), 1.51 (m, 2H). ES-MS (m/z) 389 [M+1]+.

1. stirringAfter stirring at ambient temperature for 4 h
2. extractionthe mixture was extracted with ether (3×)
3. additionThe aqueous fraction was added to aqueous 6 N sodium hydroxide (30 mL)
4. extractionThe solution was extracted with ethyl acetate (3×)
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. customevaporated
8. customThe residue was purified by flash chromatography on silica
9. washpretreated with 2% triethylamine/ethyl acetate elution
10. concentrationThe desired fractions were concentrated
11. dissolutiondissolved in ethyl acetate
12. washwashed with aqueous sodium bicarbonate
13. dry with materialdried over anhydrous sodium sulfate
14. filtrationfiltered
15. customevaporated which