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 921816Notes

Reaction equation

HRID 921816 reaction equation
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

Participants

5

Reactant 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

Product 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-carboxylateYield 87.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-22d623cc557143a8bb20b7ad2d8730d8
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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