2,4-二氯-8-氟喹唑啉的合成

Synthesis of 2,4-dichloro-8-fluoroquinazoline

由7-氟靛红(I)出发,一锅煮进行NaOH酰胺水解、双氧水氧化脱羧、酸化得到2-氨基-3-氟苯甲酸(IV)。然后以水为溶剂,一锅煮进行2-氨基与异氰酸钾成脲、强碱条件下成喹唑啉环、酸化得到8-氟喹唑啉-2,4-二酮(VII)。最后,化合物(VII)羟基氯代,得到了目标化合物2,4-二氯-8-氟喹唑啉(VIII),总收率为60.2%。通过LC-MS测试W(VIII)=98.6%。该方法成本低,反应条件温和、可控,适合于工业化制备该化合物。

Hydrolysis of 7-fluoroindoline-2,3-dione(I)with 3N NaOH,and oxidative decarboxylation with H2O2(30%),acidification with 3M hydrochloric acid were conducted in one-pot synthesis to yield 2-amino-3-fluorobenzoic acid(IV);then 2-amino group was coupled with potassium cynate to form the urea and subsequently cyclized with NaOH to give the momo-sodium of benzolyene urea and acidified with HOAc in one-pot synthesis to yield 8-fluoroquinazoline-2,4(1H,3H)-dione(VII);Fianlly,two-OH groups were chlorated with POCl3.2,4-dichloro-8-fluoroquinazoline(VIII)was obtained in 60.2%overall yield with 98.6%purity.The route is especially suitable for industry production with low cost,mild and controllable reaction conditions.