Acryloyl chloride → N-((1S,2R)-2-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)cyclohexyl)acrylamide

HRID 56370Notes

Reaction equation

HRID 56370 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([Cl:12])[C:3]=1[C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[C:18]([NH:23][C@H:24]1[C@@H:28]([NH2:29])[CH2:27]OC1)[N:17]=[CH:16]2.CCN(C(C)C)[CH:33]([CH3:35])[CH3:34].[C:39](Cl)(=[O:42])[CH:40]=[CH2:41]>ClCCl>[Cl:12][C:4]1[C:5]([O:10][CH3:11])=[CH:6][C:7]([O:8][CH3:9])=[C:2]([Cl:1])[C:3]=1[C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[C:18]([NH:23][C@@H:24]1[CH2:35][CH2:33][CH2:34][CH2:27][C@@H:28]1[NH:29][C:39](=[O:42])[CH:40]=[CH2:41])[N:17]=[CH:16]2

Participants

5

Reactant 3

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 118036616(3S,4R)-N3-(6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)tetrahydrofuran-3,4-diamine

Product 1

HCID 118036400N-((1S,2R)-2-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)cyclohexyl)acrylamideYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3S,4R)—N3-(6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)tetrahydrofuran-3,4-diamine (0.94 g, 2.1 mmol) in dichloromethane (25 mL) at 0° C. was added DIEA (0.37 mL, 2.1 mmol) and acryloyl chloride (0.17 mL, 2.1 mmol) and the reaction was stirred for 3 h. LC-MS indicated complete consumption of SM. The reaction mixture was purified by silica gel chromatography to yield N-((1S,2R)-2-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)cyclohexyl)acrylamide (Compound 27) (0.8 g, 76%). MS (ES+) C23H22Cl2N4O4 requires: 488, found: 489

Workup

  1. customconsumption of SM
  2. customThe reaction mixture was purified by silica gel chromatography

Sources & evidence

ORD record
ord-ebd712d486cf46c5841e73875fff4362
Source dataset
uspto-grants-2016_09
Patent number
US09434700B2

Reaction notes

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