反应详情

To a stirred solution of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(hydroxymethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.70 g, 1.475 mmol) and diphenyl phosphorazidate (0.381 ml, 1.770 mmol) in toluene (10 mL) was added DBU (0.222 ml, 1.475 mmol) at 0° C. After 2 h, cold bath was removed, stirred for 22 h at rt. LCMS at 8 and 22 h is same and incomplete. So, added THF (10 mL) to the turbid reaction mixture and heated at 55° C. for 5 h. Then diluted with Et2O (100 mL), washed with water (2×10 mL), brine (10 mL), dried (MgSO4), filtered, concentrated and purified by flash chromatography using 15 and 20% EtOAc/Hex to provide (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(azidomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.5038 g, 1.008 mmol, 68.4% yield) as colorless viscous oil. 1H NMR (500 MHz, CDCl3) δ 6.51 (s, 1H), 6.00-6.09 (m, 1H), 5.92 (br. s., 1H), 5.46 (d, J=16.6 Hz, 1H), 5.23 (dd, J=1.4, 10.4 Hz, 1H), 4.46-4.53 (m, 2H), 4.15-4.29 (m, 2H), 4.00-4.04 (m, 2H), 2.63 (s, 3H), 1.90-2.04 (m, 3H), 1.67-1.76 (m, 1H), 1.36 (s, 3H), 1.23-1.27 (m, 12H). 4H of piperidine are missing. LCMS (M+H)=500.5.

1. customcold bath was removed
2. customat 8 and 22 h
3. additionSo, added THF (10 mL)
4. customto the turbid reaction mixture
5. temperatureheated at 55° C. for 5 h
6. washwashed with water (2×10 mL), brine (10 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated
10. custompurified by flash chromatography