反应详情

Triphenylphosphine (0.694 g, 2.65 mmol), tetrahydrofuran (2.12 mL), 2-(tert-butyloxycarbonyl)piperazinylethanol (0.610 g, 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 6N hydrochloric acid (25 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 (25 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 preparative HPLC (5–70% acetonitrile/water). The desired fractions were concentrated, dissolved in ethyl acetate, washed with aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and evaporated to give the title compound (0.132 g, 52% yield) as the bis-trifluoroacetic acid salt. 1H NMR (D2O) δ 8.26 (s, 1H), 8.12 (s, 1H), 7.61 (d, 1H), 7.37 (d, 1H), 7.31 (m, 2H), 7.19 (m, 1H), 6.90 (m, 1H), 4.35 (m, 2H), 3.62 (m, 6H), 3.52 (m, 4H). ES-MS (m/z) 390 [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 (25 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 preparative HPLC (5–70% acetonitrile/water)
9. concentrationThe desired fractions were concentrated
10. dissolutiondissolved in ethyl acetate
11. washwashed with aqueous sodium bicarbonate
12. dry with materialdried over anhydrous sodium sulfate
13. filtrationfiltered
14. customevaporated