CAJ | 학술논문

2-氨基苄腈依次经碘代、与N,N-二甲基甲酰胺二甲缩醛缩合后,与3-氯-4-(3-氟苯甲氧基)苯胺进行Dimroth重排,得到关键中间体N-[3-氯-4-[(3-氟苯基)甲氧基]苯基]-6-碘-4-喹唑啉胺,再经Suzuki偶联、还原胺化和成盐等反应制得酪氨酸激酶抑制剂拉帕替尼二(对甲苯磺酸盐)一水合物,总收率约10%.
2-안기변정의차경전대、여N,N-이갑기갑선알이갑축철축합후,여3-록-4-(3-불분갑양기)분알진행Dimroth중배,득도관건중간체N-[3-록-4-[(3-불분기)갑양기]분기]-6-전-4-규서람알,재경Suzuki우련、환원알화화성염등반응제득락안산격매억제제랍파체니이(대갑분광산염)일수합물,총수솔약10%.
Lapatinib di-p-tosylate monohydrate, a tyrosine kinase inhibitor was synthesized from 2-aminobenzonitrile by iodination, condensation with N,N-dimethylformamide dimethyl acetal and Dimroth rearrangement with 3-chloro-4-[(3-fluorophenyl)methoxy] aniline to give the key intermediate N-[3-chloro-4-[(3-fluorophenyl) methoxy] phenyl]-6-iodoquinazolin-4-amine, which was subjected to Suzuki coupling reaction, reductive amination and salt formation with an overall yield of about 10 %.