Acryloyl chloride → N-{2-[2-Dimethylaminoethyl-methylamino]-4-methoxy-5-[(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]phenyl}prop-2-enamide

HRID 1842662Notes

Reaction equation

HRID 1842662 reaction equation
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[CH3:6][N:7]([CH3:37])[CH2:8][CH2:9][N:10]([CH3:36])[C:11]1[C:12]([NH2:35])=[CH:13][C:14]([NH:19][C:20]2[N:25]=[C:24]([C:26]3[CH:27]=[N:28][N:29]4[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=34)[CH:23]=[CH:22][N:21]=2)=[C:15]([O:17][CH3:18])[CH:16]=1>C(Cl)Cl.CO.C(Cl)Cl>[CH3:37][N:7]([CH3:6])[CH2:8][CH2:9][N:10]([CH3:36])[C:11]1[CH:16]=[C:15]([O:17][CH3:18])[C:14]([NH:19][C:20]2[N:25]=[C:24]([C:26]3[CH:27]=[N:28][N:29]4[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=34)[CH:23]=[CH:22][N:21]=2)=[CH:13][C:12]=1[NH:35][C:1](=[O:4])[CH:2]=[CH2:3]

Participants

5

Reactant 2

HCID 13140Acryloyl chlorideHCID 86677313N1-(2-dimethylaminoethyl)-5-methoxy-N1-methyl-N4-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,2,4-triamine2×

Product 1

HCID 86677312N-{2-[2-Dimethylaminoethyl-methylamino]-4-methoxy-5-[(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]phenyl}prop-2-enamideYield 63.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 21226129Dichloromethane methanolSolvent

Procedure

A solution of acryloyl chloride (63 μL, 0.78 mmol) in CH2Cl2 (3.60 mL) was added dropwise over 5 minutes to N1-(2-dimethylaminoethyl)-5-methoxy-N1-methyl-N4-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,2,4-triamine (Intermediate 158, 320 mg, 0.74 mmol) in CH2Cl2 (10.8 mL), which was cooled in an ice/CH3OH bath. The mixture was stirred for 0.5 h, and was then diluted with 10% CH3OH/CH2Cl2. The resulting solution was washed with sat. NaHCO3, dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 0-5% methanolic ammonia in CH2Cl2 gave the title compound (228 mg, 63%) as a pale pink solid after trituration with diethyl ether; 1H NMR: 2.22 (6H, s), 2.33 (2H, t), 2.74 (3H, s), 2.91 (2H, t), 3.82 (3H, s), 5.73 (1H, dd), 6.19 (1H, dd), 6.41 (1H, dd), 7.02-7.06 (2H, m), 7.25 (1H, d), 7.29-7.34 (1H, m), 8.17 (1H, s), 8.34 (1H, d), 8.44 (1H, d), 8.75-8.79 (2H, m), 8.82 (1H, s), 10.06 (1H, br s); m/z: ES+ MH+ 487.72.

Workup

  1. temperaturewas cooled in an ice/CH3OH bath
  2. washThe resulting solution was washed with sat. NaHCO3
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification by FCC
  6. washeluting with 0-5% methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-e1ba493d459b49ed90e677b9b32546ea
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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