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Ethyl Acetate → (+/-)-2-((2-Chloro-5-cyano-3-(2-(hydroxymethyl)morpholino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921911
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HRID 921911 반응식
[Si]([O:8][CH2:9][CH:10]1[CH2:15][N:14]([C:16]2[C:17]([Cl:49])=[C:18]([NH:24][C:25]3[N:30]=[C:29]([N:31]([CH:41]4[CH2:43][CH2:42]4)[CH2:32][C:33]4[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=4)[C:28]4=[N:44][CH:45]=[C:46]([C:47]#[N:48])[N:27]4[N:26]=3)[CH:19]=[C:20]([C:22]#[N:23])[CH:21]=2)[CH2:13][CH2:12][O:11]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].[Cl-].[NH4+].C(OCC)(=O)C>C1COCC1>[Cl:49][C:17]1[C:16]([N:14]2[CH2:13][CH2:12][O:11][CH:10]([CH2:9][OH:8])[CH2:15]2)=[CH:21][C:20]([C:22]#[N:23])=[CH:19][C:18]=1[NH:24][C:25]1[N:30]=[C:29]([N:31]([CH:41]2[CH2:43][CH2:42]2)[CH2:32][C:33]2[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=2)[C:28]2=[N:44][CH:45]=[C:46]([C:47]#[N:48])[N:27]2[N:26]=1
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참가 물질

6

반응물 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 89922952HCID 89922952, 화합물

생성물 1

HCID 89922871(+/-)-2-((2-Chloro-5-cyano-3-(2-(hydroxymethyl)morpholino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile수율 70.2%

시약·촉매·용매

1
HCID 8028Tetrahydrofuran용매

실험 절차

To around bottom flask charged with (+/−)-2-((3-(2-(((tert-butyldimethylsilyl)oxy)methyl)morpholino)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (1.576 g, 2.251 mmol) in THF (11.26 ml) was added TBAF (3.38 ml, 3.38 mmol). The reaction mixture was stirred at room temperature 2.5 h. The reaction mixture was poured into a separatory funnel containing 1:1 saturated aqueous ammonium chloride and ethyl acetate. The aqueous layer was extracted with ethyl acetate (2×). The combined organics were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude solid was taken up in minimal dichloromethane and purified by column chromatography on the ISCO system (80 g, 0-50% EtOAc/CH2Cl2). (+/−)-2-((2-Chloro-5-cyano-3-(2-(hydroxymethyl)morpholino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (0.926 g) was isolated as a yellow solid.

후처리

  1. additionThe reaction mixture was poured into a separatory funnel
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×)
  3. dry with materialThe combined organics were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified by column chromatography on the ISCO system (80 g, 0-50% EtOAc/CH2Cl2)

출처 및 근거

ORD 기록
ord-1ba1f5ad9dbd482cac18fa42c98969bf
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09273057B2

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