Acryloyl chloride → N-(2-{2-Dimethylaminoethyl-methylamino}-4-methoxy-5-{[5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide

HRID 1842629Notes

Reaction equation

HRID 1842629 reaction equation
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[CH3:6][N:7]([CH3:39])[CH2:8][CH2:9][N:10]([CH3:38])[C:11]1[C:12]([NH2:37])=[CH:13][C:14]([NH:19][C:20]2[N:25]=[C:24]([C:26]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[N:28]([CH3:35])[CH:27]=3)[C:23]([CH3:36])=[CH:22][N:21]=2)=[C:15]([O:17][CH3:18])[CH:16]=1.CCN(C(C)C)C(C)C>C1COCC1.O>[CH3:39][N:7]([CH3:6])[CH2:8][CH2:9][N:10]([CH3:38])[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[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[N:28]([CH3:35])[CH:27]=3)[C:23]([CH3:36])=[CH:22][N:21]=2)=[CH:13][C:12]=1[NH:37][C:1](=[O:4])[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 86677254N1-(2-dimethylaminoethyl)-5-methoxy-N1-methyl-N4-[5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,2,4-triamine2×

Product 1

HCID 86677253N-(2-{2-Dimethylaminoethyl-methylamino}-4-methoxy-5-{[5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamideYield 57%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Acryloyl chloride (0.026 mL, 1M in THF, 0.32 mmol) was added dropwise to a mixture of N1-(2-dimethylaminoethyl)-5-methoxy-N1-methyl-N4-[5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,2,4-triamine (Intermediate 81, 147 mg, 0.32 mmol) and DIPEA (0.061 mL, 0.35 mmol) in THF (15 mL) at 0° C. under N2. The resulting suspension was stirred at 0° C. for 1 h then allowed to warm to r.t. The mixture was then diluted with water (15 mL) and concentrated in vacuo. The resulting material was dissolved in a mixture of CH2Cl2 (20 mL) and CH3OH (5 mL). The resulting solution was washed with water and sat. brine, and was then dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 1-8% 7M methnaolic ammonia in CH2Cl2 gave a yellow dry film after concentrating the appropriate fractions in vacuo. This material was dissolved in CH2Cl2 and the resulting solution was diluted with diethyl ether. This was concentrated in vacuo and dried to give the title compound (93 mg, 57%) as a beige solid; 1H NMR: 2.21 (6H, s), 2.28-2.34 (2H, m), 2.37 (3H, s), 2.73 (3H, s), 2.89 (2H, t), 3.81 (3H, s), 3.89 (3H, s), 5.72 (1H, dd), 6.19 (1H, dd), 6.38 (1H, dd), 7.02 (1H, d), 7.06 (1H, d), 7.18-7.23 (1H, m), 7.48 (1H, d), 7.91 (1H, s), 8.06 (1H, s), 8.22 (1H, s), 8.36 (1H, d), 8.75 (1H, s), 10.11 (1H, s); m/z: ES+ MH+ 514.36.

Workup

  1. temperatureto warm to r.t
  2. concentrationconcentrated in vacuo
  3. dissolutionThe resulting material was dissolved in a mixture of CH2Cl2 (20 mL) and CH3OH (5 mL)
  4. washThe resulting solution was washed with water and sat. brine
  5. dry with materialwas then dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customPurification by FCC
  8. washeluting with 1-8% 7M methnaolic ammonia in CH2Cl2
  9. customgave a yellow dry film
  10. concentrationafter concentrating the appropriate fractions in vacuo
  11. dissolutionThis material was dissolved in CH2Cl2
  12. additionthe resulting solution was diluted with diethyl ether
  13. concentrationThis was concentrated in vacuo
  14. customdried

Sources & evidence

ORD record
ord-82d6df75d7684564a3d7143961666635
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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