446292-07-5
446292-07-5 結(jié)構(gòu)式
基本信息
利伐沙班雜質(zhì)39
利伐沙班雜質(zhì)50
利伐沙班脫羰基雜質(zhì)
利伐沙班氧代鄰苯二甲酰亞胺脫羰基雜質(zhì)
4-[((2R)-羥基-3-鄰苯二甲酰亞胺)丙胺]苯基-3-嗎啉
氫-異吲哚-1,3(2H)-二酮,2-[(2R)的-2-羥基-3-[[4-(3-氧-4-嗎啉基
2-[(2R)-2-羥基-3-[[4-(3-氧代-4-嗎啉基)苯基]氨基]丙基]-1H-異吲哚-1,3(2H)-二酮
2-[(2R)-2-羥基-3-[[4-(3-氧代-4-嗎啉基)苯基]氨基]丙基]-1H-異吲哚-1,3(2H)-二酮,利伐沙班中間體
2-[(2R)-2-羥基-3-[[4-(3-氧代-4-嗎啉基)苯基]氨基]丙基]-1H-異吲哚-1,3(2H)-二酮,利伐沙班中間體 1KG
Rivaroxaban interMediate B
-2-(2-Hydroxy-3-((4-(3-oxomorpholino)
Rivaroxaban Phthalimido Descarbonyl Impurity
4-[((2R)-Hydroxy-3-phthaliMido)propylaMine]phenyl-3-Morpholinone
2-[(2R)-2-HYDROXY-3-[[4-(3-OXO-4-MORPHOLINYL)PHENYL]AMINO]PROPYL]-
2-[(2R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)anilino]propyl]isoindole-1,3-dione
(R)-2-(2-Hydroxy-3-((4-(3-oxomorpholino)phenyl)-amino)propyl)isoindoline-1,3-dione
2-[(2R)-2-Hydroxy-3-[[4-(3-oxo-4-morpholinyl)phenyl]amino]propyl]-1H-isoindole-1,3(2H)-dione
2-[(2R)-2-hydroxy-3-{[4-(3-oxoMorpholin-4-yl)phenyl]aMino}p ropyl]-1H-isoindole-1,3(2H)-dione
物理化學(xué)性質(zhì)
制備方法
1252018-10-2
1074-82-4
446292-07-5
實(shí)施例3：(R)-2-(2-羥基-3-((4-(3-氧代嗎啉)苯基)氨基)丙基)異吲哚啉-1,3-二酮(7a)的制備：將鄰苯二甲酰亞胺鉀鹽(7.16 g, 38.632 mmol)一次性加入到機(jī)械攪拌的4-[4-(N-(3-氯-2R-羥基-1-丙基)氨基)苯基]嗎啉-3-酮(10 g, 35.119 mmol)的N,N-二甲基甲酰胺(DMF, 60 mL)溶液中。將懸浮液在室溫下攪拌后，加熱至100℃，并在該溫度下持續(xù)攪拌3小時(shí)。反應(yīng)完成后，將混合物冷卻至室溫。加入水(60 mL)并將懸浮液繼續(xù)攪拌15分鐘。隨后，將懸浮液通過(guò)布氏漏斗過(guò)濾，收集固體產(chǎn)物。用蒸餾水(2×40 mL)洗滌固體，并在50℃下真空干燥10小時(shí)，得到目標(biāo)產(chǎn)物(R)-2-(2-羥基-3-((4-(3-氧代嗎啉)苯基)氨基)丙基)異吲哚啉-1,3-二酮(12.55 g, 產(chǎn)率93%)，為白色結(jié)晶固體。1H NMR (400 MHz, DMSO-d6) δ: 2.99-3.05 (m, 1H), 3.14-3.2 (m, 1H), 3.59-3.69 (m, 4H), 3.91-3.94 (m, 2H), 3.97-4.05 (m, 1H), 4.14 (s, 2H), 5.16 (d, J = 5.2 Hz, 1H), 5.66 (t, J = 6.0 Hz, 1H), 6.61 (d, J = 8.7 Hz, 2H), 7.03 (d, J = 8.8 Hz, 2H), 7.82-7.88 (m, 4H)。
參考文獻(xiàn)：
[1] Patent: WO2012/51692, 2012, A1. Location in patent: Page/Page column 42-43
[2] Patent: CN103951661, 2017, B. Location in patent: Paragraph 0043-0044
[3] Patent: CN104974105, 2017, B. Location in patent: Paragraph 0073
[4] Patent: CN104974149, 2018, B. Location in patent: Paragraph 0074; 0075; 0077; 0081; 0083
[5] Patent: WO2012/32533, 2012, A2. Location in patent: Page/Page column 15