Acryloyl chloride → N-(2-[3-Dimethylaminoazetidin-1-yl]-5-{[4-(1H-indol-3-yl)pyrimidin-2-yl]amino}-4-methoxyphenyl)prop-2-enamide

HRID 1842666Notes

Reaction equation

HRID 1842666 reaction equation
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[CH3:6][N:7]([CH3:37])[CH:8]1[CH2:11][N:10]([C:12]2[CH:17]=[C:16]([O:18][CH3:19])[C:15]([NH:20][C:21]3[N:26]=[C:25]([C:27]4[C:35]5[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=5)[NH:29][CH:28]=4)[CH:24]=[CH:23][N:22]=3)=[CH:14][C:13]=2[NH2:36])[CH2:9]1>C(Cl)Cl>[CH3:37][N:7]([CH3:6])[CH:8]1[CH2:9][N:10]([C:12]2[CH:17]=[C:16]([O:18][CH3:19])[C:15]([NH:20][C:21]3[N:26]=[C:25]([C:27]4[C:35]5[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=5)[NH:29][CH:28]=4)[CH:24]=[CH:23][N:22]=3)=[CH:14][C:13]=2[NH:36][C:1](=[O:4])[CH:2]=[CH2:3])[CH2:11]1

Participants

4

Reactant 2

HCID 13140Acryloyl chlorideHCID 866773214-(3-Dimethylaminoazetidin-1-yl)-N-[4-(1H-indol-3-yl)pyrimidin-2-yl]-6-methoxybenzene-1,3-diamine2×

Product 1

HCID 86677320N-(2-[3-Dimethylaminoazetidin-1-yl]-5-{[4-(1H-indol-3-yl)pyrimidin-2-yl]amino}-4-methoxyphenyl)prop-2-enamideYield 18.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-5 °C

Procedure

A solution of acryloyl chloride (0.522 mL, 1M in CH2Cl2, 0.52 mmol) was added dropwise to 4-(3-dimethylaminoazetidin-1-yl)-N-[4-(1H-indol-3-yl)pyrimidin-2-yl]-6-methoxy-benzene-1,3-diamine (Intermediate 166, 224 mg, 0.52 mmol) in CH2Cl2 (10 mL) and the mixture was then stirred at −5° C. for 1 h. The mixture was then diluted with CH2Cl2 (100 mL), and the resulting solution was washed with sat. NaHCO3 (25 mL), water (25 mL), and then sat. brine (25 mL) and then concentrated in vacuo. Purification by FCC, eluting with 0-30% CH3OH in CH2Cl2 gave the title compound (46 mg, 18%) as a beige solid; 1H NMR: 2.09 (6H, d), 3.09 (1H, s), 3.56 (2H, t), 3.85 (3H, s), 3.96 (2H, t), 5.68 (1H, dd), 6.20 (1H, dd), 6.26 (1H, s), 6.50 (1H, dd), 7.14 (2H, dt), 7.18 (1H, t), 7.40-7.46 (1H, m), 7.82 (1H, s), 7.90 (1H, s), 8.23 (1H, d), 8.31 (1H, d), 8.38 (1H, d), 9.34 (1H, s), 11.76 (1H, s); m/z: ES+ MH+ 484.

Workup

  1. washthe resulting solution was washed with sat. NaHCO3 (25 mL), water (25 mL)
  2. concentrationsat. brine (25 mL) and then concentrated in vacuo
  3. customPurification by FCC
  4. washeluting with 0-30% CH3OH in CH2Cl2

Sources & evidence

ORD record
ord-6fc55010bb744bedbae3912c34a14a55
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

Loading…