Tetrabutylammonium Fluoride → 2-chloro-N-((3R,4R)-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)-3-hydroxypiperidin-4-yl)acetamide

HRID 1430861ノート

反応式

HRID 1430861 の反応式
[Si]([O:8][C@H:9]1[C@H:14]([NH:15][C:16](=[O:19])[CH2:17][Cl:18])[CH2:13][CH2:12][N:11]([C:20]2[CH:25]=[C:24]([C:26]#[N:27])[CH:23]=[C:22]([NH:28][C:29]3[N:34]=[C:33]([N:35]([CH:45]4[CH2:47][CH2:46]4)[CH2:36][C:37]4[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=4)[C:32]4=[N:48][CH:49]=[C:50]([C:51]#[N:52])[N:31]4[N:30]=3)[C:21]=2[Cl:53])[CH2:10]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:18][CH2:17][C:16]([NH:15][C@@H:14]1[CH2:13][CH2:12][N:11]([C:20]2[CH:25]=[C:24]([C:26]#[N:27])[CH:23]=[C:22]([NH:28][C:29]3[N:34]=[C:33]([N:35]([CH:45]4[CH2:47][CH2:46]4)[CH2:36][C:37]4[CH:38]=[CH:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=4)[C:32]4=[N:48][CH:49]=[C:50]([C:51]#[N:52])[N:31]4[N:30]=3)[C:21]=2[Cl:53])[CH2:10][C@H:9]1[OH:8])=[O:19]

参加物

4

反応物 2

HCID 2724141Tetrabutylammonium FluorideHCID 86708552HCID 86708552、化合物

生成物 1

HCID 867085532-chloro-N-((3R,4R)-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)-3-hydroxypiperidin-4-yl)acetamide収率 60.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To (+/−)-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-chloroacetamide (43 mg, 0.055 mmol) in THF (1 mL) was added TBAF (1M in THF, 0.112 mL, 0.112 mmol) and the reaction solution was stirred at room temperature overnight. LCMS showed completion of reaction. Solvent was evaporated and the crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 0.5-4% methanol/dichloromethane) to give (+/−)-2-chloro-N-((3R,4R)-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)-3-hydroxypiperidin-4-yl)acetamide (22 mg) as a white solid.

後処理

  1. customcompletion of reaction
  2. customSolvent was evaporated
  3. customthe crude product was purified by flash chromatography on silica gel using
  4. washan automated ISCO system (24 g column, eluting with 0.5-4% methanol/dichloromethane)

出典と根拠

ORDレコード
ord-e5eddba66cbd44749711610f20664dd4
出典データセット
uspto-grants-2015_01
特許番号
US08940736B2

反応ノート

読み込み中…