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4-Morpholineacetic acid → (+/-)-N-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)-2-morpholinoacetamide

HRID 1430832
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HRID 1430832 반응식
[NH2:1][C@@H:2]1[CH2:7][CH2:6][N:5]([C:8]2[C:9]([Cl:41])=[C:10]([NH:16][C:17]3[N:22]=[C:21]([N:23]([CH:33]4[CH2:35][CH2:34]4)[CH2:24][C:25]4[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=4)[C:20]4=[N:36][CH:37]=[C:38]([C:39]#[N:40])[N:19]4[N:18]=3)[CH:11]=[C:12]([C:14]#[N:15])[CH:13]=2)[CH2:4][C@H:3]1[O:42][Si:43]([C:46]([CH3:49])([CH3:48])[CH3:47])([CH3:45])[CH3:44].[O:50]1[CH2:55][CH2:54][N:53]([CH2:56][C:57](O)=[O:58])[CH2:52][CH2:51]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.ClCCl>[Si:43]([O:42][C@H:3]1[C@H:2]([NH:1][C:57](=[O:58])[CH2:56][N:53]2[CH2:54][CH2:55][O:50][CH2:51][CH2:52]2)[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[C:12]([C:14]#[N:15])[CH:11]=[C:10]([NH:16][C:17]3[N:22]=[C:21]([N:23]([CH:33]4[CH2:34][CH2:35]4)[CH2:24][C:25]4[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=4)[C:20]4=[N:36][CH:37]=[C:38]([C:39]#[N:40])[N:19]4[N:18]=3)[C:9]=2[Cl:41])[CH2:4]1)([C:46]([CH3:49])([CH3:48])[CH3:47])([CH3:45])[CH3:44]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 3

HCID 4389684-Morpholineacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86708507(+/-)-2-((3-((3R,4R)-4-amino-3-((tert-butyldimethyl silyl)oxy) piperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

생성물 1

HCID 86708512
(+/-)-N-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)-2-morpholinoacetamide
수율 97.6%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

A mixture of (+/−)-2-((3-((3R,4R)-4-amino-3-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 171E, 40 mg, 0.057 mmol), 2-morpholinoacetic acid (9.96 mg, 0.069 mmol) and HATU (26.1 mg, 0.069 mmol) in DMF (1 mL) was stirred at room temperature for 6 h. The reaction mixture was diluted with dichloromethane and was filtered. The filtrate was concentrated in vacuo and the crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 5-50% ethyl acetate/hexanes). (+/−)-N-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)-2-morpholinoacetamide (46 mg) was obtained as a white solid.

후처리

  1. filtrationwas filtered
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe crude product was purified by flash chromatography on silica gel using
  4. washan automated ISCO system (24 g column, eluting with 5-50% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-47e68d5a942440c59b3e19bb4b030751
출처 데이터셋
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08940736B2

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