Acryloyl chloride → N-(4-Methoxy-2-{1-methyl-3,6-dihydro-2H-pyridin-4-yl}-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide

HRID 1842656Notes

Reaction equation

HRID 1842656 reaction equation
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[CH3:6][O:7][C:8]1[CH:13]=[C:12]([C:14]2[CH2:15][CH2:16][N:17]([CH3:20])[CH2:18][CH:19]=2)[C:11]([NH2:21])=[CH:10][C:9]=1[NH:22][C:23]1[N:28]=[C:27]([C:29]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[N:31]([CH3:38])[CH:30]=2)[CH:26]=[CH:25][N:24]=1>C(Cl)Cl.CO.C(Cl)Cl>[CH3:6][O:7][C:8]1[C:9]([NH:22][C:23]2[N:28]=[C:27]([C:29]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:31]([CH3:38])[CH:30]=3)[CH:26]=[CH:25][N:24]=2)=[CH:10][C:11]([NH:21][C:1](=[O:4])[CH:2]=[CH2:3])=[C:12]([C:14]2[CH2:15][CH2:16][N:17]([CH3:20])[CH2:18][CH:19]=2)[CH:13]=1

Participants

5

Reactant 2

HCID 13140Acryloyl chlorideHCID 866773014-methoxy-6-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-N'-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamine2×

Product 1

HCID 86677300N-(4-Methoxy-2-{1-methyl-3,6-dihydro-2H-pyridin-4-yl}-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamideYield 32%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 21226129Dichloromethane methanolSolvent

Procedure

A solution of acryloyl chloride (37 μL, 0.45 mmol) in CH2Cl2 (2.32 mL) was added dropwise over 5 minutes to 4-methoxy-6-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-N′-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamine (Intermediate 143, 189 mg, 0.43 mmol) in CH2Cl2 (5.8 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 0-20% CH3OH in CH2Cl2 gave the title compound (67 mg, 32%) as an pale yellow solid after trituration with diethyl ether; 1H NMR: 2.29 (3H, s), 2.36-2.41 (2H, m), 2.53-2.58 (2H, m), 2.98-3.02 (2H, m), 3.90 (3H, s), 3.91 (3H, s), 5.69-5.73 (2H, m), 6.22 (1H, dd), 6.52 (1H, dd), 6.86 (1H, s), 7.20-7.28 (3H, m), 7.52-7.55 (1H, m), 7.88 (1H, s), 8.33-8.37 (2H, m), 8.43 (1H, s), 8.45 (1H, s), 9.34 (1H, s); m/z: ES+ MH+ 495.70.

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 0-20% CH3OH in CH2Cl2

Sources & evidence

ORD record
ord-77103039a50c427a86acfe26016b56f9
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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