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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
ノート
印刷プレビュー

反応式

HRID 921911 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 89922952HCID 89922952、化合物

生成物 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-carbonitrile収率 70.2%

試薬・触媒・溶媒

1
HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-1ba1f5ad9dbd482cac18fa42c98969bf
出典データセット
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09273057B2

反応ノート

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