反应详情

温度

100 °C

3-(4-Oxo-3,4-dihydrophthalazin-1-ylmethyl)benzoic acid (A)(5.0 g, 0.17 mol), tert-butyl 1-piperazinecarboxylate (3.9 g, 0.21 mol), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) (8.6 g, 0.22 mol) and N,N,-diisopropylethylamine (6.7 ml, 0.38 mol) were added to dimethylacetamide (40 ml) and stirred for 18 hours. Water (100 ml) was added and the reaction mixture was heated to 100° C. for 1 hour. The suspension was cooled to room temperature, filtered and dried to yield a white solid. The solid was dissolved in a solution of 6M HCl and ethanol (2:1, 50 ml) and stirred for 1 hour. The reaction was concentrated, basified with ammonia to pH 9, and the product was extracted into dichloromethane (2×50 ml). The combined organic layers were washed with water (2×50 ml), dried over MgSO4, and evaporated in vacuo to yield 4-[3-(piperazine-1-carbonyl)benzyl]-2H-phthalazin-1-one (1) as a yellow crystalline solid (4.0 g, 77%); m/z [M+1]+ 349 (97% purity), δH 2.6-3.8 (8H, m), 4.4 (2H, s), 7.2-7.5 (4H, m), 7.7 -8.0 (3H, m), 8.2-8.3 (1H, m), 12.6 (1H, s)

1. temperatureThe suspension was cooled to room temperature
2. filtrationfiltered
3. customdried
4. customto yield a white solid
5. stirringstirred for 1 hour
6. concentrationThe reaction was concentrated
7. extractionthe product was extracted into dichloromethane (2×50 ml)
8. washThe combined organic layers were washed with water (2×50 ml)
9. dry with materialdried over MgSO4
10. customevaporated in vacuo