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

HRID 1842642Notes

Reaction equation

HRID 1842642 reaction equation
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[Cl:6][C:7]1[C:8]([C:34]2[CH:35]=[N:36][N:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=23)=[N:9][C:10]([NH:13][C:14]2[CH:15]=[C:16]([NH2:33])[C:17]([N:22]([CH3:32])[CH2:23][CH2:24][N:25]3[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]3)=[CH:18][C:19]=2[O:20][CH3:21])=[N:11][CH:12]=1>C(Cl)Cl>[Cl:6][C:7]1[C:8]([C:34]2[CH:35]=[N:36][N:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=23)=[N:9][C:10]([NH:13][C:14]2[C:19]([O:20][CH3:21])=[CH:18][C:17]([N:22]([CH3:32])[CH2:23][CH2:24][N:25]3[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]3)=[C:16]([NH:33][C:1](=[O:4])[CH:2]=[CH2:3])[CH:15]=2)=[N:11][CH:12]=1

Participants

4

Reactant 2

HCID 13140Acryloyl chlorideHCID 86677275N4-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-5-methoxy-N1-methyl-N1-[2-(4-methylpiperazin-1-yl)ethyl]benzene-1,2,4-triamine2×

Product 1

HCID 86677274N-(5-{[5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl]amino}-4-methoxy-2-{methyl-[2-(4-methylpiperazin-1-yl)ethyl]amino}phenyl)prop-2-enamideYield 63.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of acryloyl chloride (0.028 mL, 0.35 mmol) in CH2Cl2 (1 mL) was added dropwise to a stirred mixture of N4-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-5-methoxy-N1-methyl-N1-[2-(4-methylpiperazin-1-yl)ethyl]benzene-1,2,4-triamine (Intermediate 107, 0.174 g, 0.33 mmol) in CH2Cl2 (2.5 mL) under N2. The mixture was then stirred at r.t. for 1 h and was then diluted with CH2Cl2 (25 mL). This solution was washed with sat. NaHCO3 (25 mL) and the aqueous wash solution was extracted with CH2Cl2 (20 mL). The combined organic solutions were dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 0-8% CH3OH in CH2Cl2 gave the title compound (0.12 g, 63%) as a beige foam; 1H NMR: (CDCl3) 2.31 (3H, s), 2.35-2.6 (10H, m), 2.67 (3H, s), 3.00 (2H, t), 3.88 (3H, s), 5.64-5.82 (1H, m), 6.31-6.50 (2H, m), 6.79 (1H, s), 6.91 (1H, t), 7.29 (1H, t), 7.48 (1H, s), 8.47 (1H, s), 8.54 (2H, t), 8.94 (1H, s), 9.15 (1H, s), 9.38 (1H, s); m/z: ES+ MH+ 576.59.

Workup

  1. washThis solution was washed with sat. NaHCO3 (25 mL)
  2. extractionthe aqueous wash solution was extracted with CH2Cl2 (20 mL)
  3. dry with materialThe combined organic solutions were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification by FCC
  6. washeluting with 0-8% CH3OH in CH2Cl2

Sources & evidence

ORD record
ord-f7f67497c4f544cd8a90afd0b8f2d5a5
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

Loading…