反应详情

A mixture of 2-amino-6-chloropurine (890 mg, 4.2 mmol), diethyl 2-hydroxyethoxymethane-phosphonate 2b (710 mg, 4.2 mmol) and triphenylphosphine (1.65 g, 6.3 mmol) in anhydrous DMF (10 mL) was stirred at ambient temperature under N2 for 30 min. The reaction mixture was then cooled to -10° C. and diethyl azodicarboxylate (0.67 mL, 4.2 mmol) in DMF (2 mL) was added dropwise at such a rate that the reaction temperature was maintained at -10° C. The reaction mixture was stirred at that temperature for 2 h and then allowed to warm to ambient temperature gradually and stirred for 5 h. Any unreacted 2-amino-6-chloropurine was removed by filtration and the solvent removed under vacuum. The crude product was purified by silica gel column chromatography, eluting with CH2Cl2 /MeOH (9:1), to afford 650 mg (42 % yield) of the desired N9 -product 1d. 1H NMR (CDCl3) δ 7.90 (s, 1 H, H-8), 5.20 (s, broad, 2 H, NH2), 4.30 (t, J=4.8 Hz, 2 H, CH2N), 4.12 (dq, J=8.4 Hz, J=7.0 Hz, 4 H, 2 OCH2CH3), 3.92 (t, J=5.0 Hz, 2 H, CH2O), 3.79 (d, J=8.4 Hz, 2 H, CH2O), 1.30 (t, J=7.1 Hz, 6 H, 2 CH3); 13C NMR (CDCl3) δ 159.20, 153.78, 151.20, 143.29, 124.99 (purine ring carbons), 70.82 (d, 2JC,P=10.3 Hz, OCH2CH3), 65.17 (d, 1JC,P=166.0 Hz, CH2P), 62.42 (d, 3JC,P=5.7 Hz, CH2O), 43.19 (CH2N), 16.27 (d, 3J,P=5.7 Hz, CH3); UV (MeOH) λmax 247 (14,600), 310 (18,300) nm; IR (KBr, cm-1) 3327 and 3210 (m, broad, NH2), 1612 and 1562 (vs, purine ring), 1229 (s, P=O), 1026 (s, P--O--C); MS (CI) m/e 366 and 364 (40.5, 100, M+1), 3328 (22.3, M--Cl); Anal. calcd. for C12H19ClN5O4P: C, 39.63; H, 5.26; N, 19.25. Found: C, 39.53; H, 5.48; N, 18.99.

1. temperatureThe reaction mixture was then cooled to -10° C.
2. temperaturewas maintained at -10° C
3. stirringThe reaction mixture was stirred at that temperature for 2 h
4. temperatureto warm to ambient temperature gradually
5. stirringstirred for 5 h
6. customAny unreacted 2-amino-6-chloropurine was removed by filtration
7. customthe solvent removed under vacuum
8. customThe crude product was purified by silica gel column chromatography
9. washeluting with CH2Cl2 /MeOH (9:1)