Acryloyl chloride → N-((1S,2R)-2-((6-(2,6-dichloro-3,5-dimethoxyphenyl)-8-ethyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)cyclopentyl)acrylamide

HRID 56387Notes

Reaction equation

HRID 56387 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:7][C:8]1[N:9]=[CH:10][C:11]2[CH:17]=[C:16]([C:18]3[C:23]([Cl:24])=[C:22]([O:25][CH3:26])[CH:21]=[C:20]([O:27][CH3:28])[C:19]=3[Cl:29])[C:15](=[O:30])[N:14]([CH2:31][CH3:32])[C:12]=2[N:13]=1.CCN(C(C)C)C(C)C.[C:42](Cl)(=[O:45])[CH:43]=[CH2:44]>ClCCl>[Cl:24][C:23]1[C:22]([O:25][CH3:26])=[CH:21][C:20]([O:27][CH3:28])=[C:19]([Cl:29])[C:18]=1[C:16]1[C:15](=[O:30])[N:14]([CH2:31][CH3:32])[C:12]2[N:13]=[C:8]([NH:7][C@@H:3]3[CH2:4][CH2:5][CH2:6][C@@H:2]3[NH:1][C:42](=[O:45])[CH:43]=[CH2:44])[N:9]=[CH:10][C:11]=2[CH:17]=1

Participants

5

Reactant 3

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 1180362122-(((1R,2S)-2-aminocyclopentyl)amino)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-8-ethylpyrido[2,3-d]pyrimidin-7(8H)-one

Product 1

HCID 118036110N-((1S,2R)-2-((6-(2,6-dichloro-3,5-dimethoxyphenyl)-8-ethyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)cyclopentyl)acrylamideYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(((1R,2S)-2-aminocyclopentyl)amino)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-8-ethylpyrido[2,3-d]pyrimidin-7(8H)-one (0.105 mmol) in dichloromethane (2.1 mL) at −20° C. was added DIEA (0.018 mL, 0.105 mmol) and acryloyl chloride (0.008 mL, 0.105 mmol) and the reaction was stirred for 1 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)-8-ethyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)cyclopentyl)acrylamide (36 mg, 65%). MS (ES+) C25H27Cl2N5O4 requires: 531, found: 532.

Workup

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

Sources & evidence

ORD record
ord-25330bbcb29c49b29ca534980826eada
Source dataset
uspto-grants-2016_09
Patent number
US09434700B2

Reaction notes

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