反应详情

A suspension of the 9-[(3aR,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d][1,3]dioxol-4-yl]-9H-purin-6-amine (1.45 g, 4.736 mmol), benzyl 3-(3-oxocyclobutyl)propanoate (1.21 g, 5.209 mmol) and acetic acid (246.45 μl, 4.31 mmol) in DCE:iPrOH (4:1, 50 ml) was stirred at RT for 1 h. A further aliquot of DCE (40 ml) and iPrOH (5 ml) was added to the reaction mixture and continued for 1 hour. STAB (1.28 g, 6.03 mmol) was then added and the reaction mixture was stirred for 18 hours. The reaction mixture was quenched with 1N Na2CO3 (10 ml), and the product was extracted with DCM (2×30 ml). This was dried over Na2SO4, filtered and evaporated to dryness. Purification by silica gel column chromatography, eluting with 7N NH3 in MeOH:DCM (1:99-3:97) gave the desired product as a colourless oil, 1.51 g (58%); MS (ESI+) for C27H34N6O5 m/z 523.65 [M+H]+; HPLC purity 97% (ret. time, 1.43 min); 1H NMR (500 MHz, CHLOROFORM-d) δH ppm 8.35 (d, J=5.3 Hz, 1H), 7.87 (d, J=33.8 Hz, 1H), 7.40-7.29 (m, 5H), 6.08-5.94 (m, 1H), 5.59-5.42 (m, 3H), 5.10 (d, J=4.0 Hz, 2H), 5.03-4.96 (m, 1H), 4.33 (dq, J=7.3, 3.9 Hz, 1H), 3.12 (ddd, J=23.0, 14.6, 7.5 Hz, 1H), 2.85-2.77 (m, 1H), 2.74 (dd, J=12.5, 6.6 Hz, 1H), 2.39-2.07 (m, 4H), 1.90-1.64 (m, 5H), 1.61 (s, 4H), 1.38 (s, 3H), 1.28-1.06 (m, 1H).

1. waitcontinued for 1 hour
2. additionSTAB (1.28 g, 6.03 mmol) was then added
3. stirringthe reaction mixture was stirred for 18 hours
4. customThe reaction mixture was quenched with 1N Na2CO3 (10 ml)
5. extractionthe product was extracted with DCM (2×30 ml)
6. dry with materialThis was dried over Na2SO4
7. filtrationfiltered
8. customevaporated to dryness
9. customPurification by silica gel column chromatography
10. washeluting with 7N NH3 in MeOH:DCM (1:99-3:97)