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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
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HRID 921816 반응식
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
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참가 물질

5

반응물 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

생성물 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-carboxylate수율 87.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-22d623cc557143a8bb20b7ad2d8730d8
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09273057B2

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