267243-68-5
267243-68-5 結(jié)構(gòu)式
基本信息
卡紐替尼中間體1
N4-(3-氯-4-氟苯基)-7-(3-嗎啉丙氧基)喹唑啉-4,6-二胺
N4-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)quinazol...
N4-(3-chloro-4-fluorophenyl)-7-(3-Morpholinopropoxy)quinazoline-4,6-diaMine
4-N-(3-chloro-4-fluorophenyl)-7-(3-morpholin-4-ylpropoxy)quinazoline-4,6-diamine
4,6-Quinazolinediamine, N4-(3-chloro-4-fluorophenyl)-7-[3-(4-morpholinyl)propoxy]-
6-amino-4-[N-(3-chloro-4-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]quinazoline
物理化學(xué)性質(zhì)
制備方法
267243-64-1
267243-68-5
以N-(3-氯-4-氟苯基)-7-(3-嗎啉代丙氧基)-6-硝基喹唑啉-4-胺（1.0當(dāng)量）和NiCl2·6H2O（2.0當(dāng)量）為原料，將其溶解于二氯甲烷/甲醇（32 mL:8 mL）混合溶劑中。將反應(yīng)混合物在0℃下攪拌5分鐘，隨后分批加入NaBH4（4.0當(dāng)量）。加畢，移除冰浴，使反應(yīng)混合物自然升溫至室溫，并繼續(xù)攪拌30分鐘。反應(yīng)完成后，通過減壓濃縮除去溶劑，得到粗產(chǎn)物。粗產(chǎn)物經(jīng)柱色譜純化（洗脫劑比例為10:1的二氯甲烷/甲醇），得到N-(3-氯-4-氟苯基)-7-(3-嗎啉代丙氧基)喹唑啉-4,6-二胺的淡黃色固體，收率為50%。1H NMR (500 MHz, DMSO) δ 9.39 (s, 1H), 8.37 (s, 1H), 8.20 (d, J = 4.5 Hz, 1H), 7.81 (d, J = 8.5 Hz, 1H), 7.41-7.38 (m, 2H), 7.08 (s, 1H), 5.35 (s, 2H), 4.20 (t, J = 5.5 Hz, 2H), 3.59 (t, J = 4.5 Hz, 4H), 3.18 (d, J = 5.0 Hz, 2H), 2.40 (s, 4H), 2.01-1.96 (m, 2H)。HRMS (ESI): m/z 計(jì)算值 (C21H23ClFN5O2 + H)+: 432.1603。實(shí)測(cè)值: 432.1613。
參考文獻(xiàn)：
[1] Patent: US6344455, 2002, B1
[2] Journal of Medicinal Chemistry, 2000, vol. 43, # 7, p. 1380 - 1397
[3] Patent: US2014/206687, 2014, A1. Location in patent: Paragraph 0323-0324
[4] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 22, p. 5916 - 5919
[5] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 16, p. 3359 - 3370