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Methyl chloroformate → methyl 5-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate

HRID 921816
ノート
印刷プレビュー

反応式

HRID 921816 の反応式
Cl[C:2]([O:4][CH3:5])=[O:3].[Cl:6][C:7]1[C:12]([N:13]2[CH2:18][CH2:17][CH:16]3[NH:19][CH2:20][CH2:21][CH:15]3[CH2:14]2)=[CH:11][C:10]([C:22]#[N:23])=[CH:9][C:8]=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:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)[C:28]2=[N:44][CH:45]=[C:46]([C:47]#[N:48])[N:27]2[N:26]=1.C(N(CC)CC)C>ClCCl>[Cl:6][C:7]1[C:8]([NH:24][C:25]2[N:30]=[C:29]([N:31]([CH:41]3[CH2:42][CH2:43]3)[CH2:32][C:33]3[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=3)[C:28]3=[N:44][CH:45]=[C:46]([C:47]#[N:48])[N:27]3[N:26]=2)=[CH:9][C:10]([C:22]#[N:23])=[CH:11][C:12]=1[N:13]1[CH2:18][CH2:17][CH:16]2[N:19]([C:2]([O:4][CH3:5])=[O:3])[CH2:20][CH2:21][CH:15]2[CH2:14]1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 899228312-((2-chloro-5-cyano-3-(hexahydro-1H-pyrrolo[3,2-c]pyridin-5(6H)-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

生成物 1

HCID 118253354methyl 5-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate収率 87.5%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Methyl chloroformate (5.66 μl, 0.073 mmol) was added to a solution of 2-((2-chloro-5-cyano-3-(hexahydro-1H-pyrrolo[3,2-c]pyridin-5(6H)-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 443F, 29 mg, 0.049 mmol) and triethylamine (0.020 ml, 0.146 mmol) in dichloromethane (2 mL) and the reaction mixture was stirred at room temperature overnight. Solvent was evaporated in vacuo and the crude intermediate was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 1-4% 2 N ammonia in methanol/dichloromethane) to give 28 mg of methyl 5-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate.

後処理

  1. customSolvent was evaporated in vacuo
  2. customthe crude intermediate was purified by flash chromatography on silica gel using
  3. washan automated ISCO system (24 g column, eluting with 1-4% 2 N ammonia in methanol/dichloromethane)

出典と根拠

ORDレコード
ord-22d623cc557143a8bb20b7ad2d8730d8
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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