Beige to yellow crystalline powder
An intermediate for the synthesis of a benzimidazole PARP inhibitor I (succinate salt) (ABT-472). Reactions with aminoquinazolinones yield phthalimidoquinazolinones.
4-Nitrophthalic Anhydride is an intermediate for the synthesis of the benzimidazole PARP inhibitor I, ABT-472. It reacts with aminoquinazolinones to yield phthalimidoquinazolinones.
3-Nitrophthalic anhydride can be prepared by heating 3-nitrophthalic acid under various conditions and by the action of acetic anhydride, essentially as in the procedure described. The direct nitration of phthalic anhydride yields 3-nitrophthalic anhydride together with the isomeric 4-nitro compound.
General procedure for the synthesis of 3-nitrophthalic anhydride from 3-nitrophthalic acid: 474.8 g (2.25 mol) of 3-nitrophthalic acid was dissolved in 450 ml of acetic anhydride and the reaction was stirred under reflux conditions for 1 hour. Upon completion of the reaction, the reaction solution was slowly cooled to 80 °C. Subsequently, 1000 ml of methyl tert-butyl ether (MTBE) was quickly added and the mixture was cooled to 15 °C to promote crystallization. The resulting solid product was separated by filtration, washed with methyl tert-butyl ether (MTBE) and finally dried in a vacuum oven at 40 °C. The yield of the reaction was 88.8%.
Crystallise it from *C6H6, *C6H6/pet ether, Me2CO, AcOH, or Ac2O (m 164-165o). Dry it at 100o. [Beilstein 17 III/IV 6149, 17/11 V 266.]
[1] Organic Letters, 2010, vol. 12, # 21, p. 4796 - 4799
[2] Bioorganic Chemistry, 2018, vol. 81, p. 373 - 381
[3] Synthetic Communications, 2016, vol. 46, # 16, p. 1343 - 1348
[4] Patent: WO2007/6566, 2007, A1. Location in patent: Page/Page column 28; 32-33
[5] Tetrahedron Letters, 2017, vol. 58, # 32, p. 3160 - 3163
