Acryloyl chloride → N-(5-{[5-Cyano-4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}-2-{2-dimethylaminoethyl-methylamino}-4-methoxyphenyl)prop-2-enamide

HRID 1842640Notes

Reaction equation

HRID 1842640 reaction equation
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[NH2:6][C:7]1[C:8]([N:34]([CH2:36][CH2:37][N:38]([CH3:40])[CH3:39])[CH3:35])=[CH:9][C:10]([O:32][CH3:33])=[C:11]([NH:13][C:14]2[N:19]=[C:18]([C:20]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]([CH3:29])[CH:21]=3)[C:17]([C:30]#[N:31])=[CH:16][N:15]=2)[CH:12]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:30]([C:17]1[C:18]([C:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22]([CH3:29])[CH:21]=2)=[N:19][C:14]([NH:13][C:11]2[C:10]([O:32][CH3:33])=[CH:9][C:8]([N:34]([CH2:36][CH2:37][N:38]([CH3:39])[CH3:40])[CH3:35])=[C:7]([NH:6][C:1](=[O:4])[CH:2]=[CH2:3])[CH:12]=2)=[N:15][CH:16]=1)#[N:31]

Participants

5

Reactant 3

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 866772712-{[5-Amino-4-(2-dimethylaminoethyl-methylamino)-2-methoxyphenyl]-amino}-4-(1-methylindol-3-yl)pyrimidine-5-carbonitrile2×

Product 1

HCID 86677270N-(5-{[5-Cyano-4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}-2-{2-dimethylaminoethyl-methylamino}-4-methoxyphenyl)prop-2-enamideYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of acryloyl chloride (0.035 mL, 0.44 mmol) in CH2Cl2 (1 mL) was added to a mixture of 2-{[5-amino-4-(2-dimethylaminoethyl-methylamino)-2-methoxyphenyl]-amino}-4-(1-methylindol-3-yl)pyrimidine-5-carbonitrile (Intermediate 102, 171 mg, 0.36 mmol) and DIPEA (0.120 mL, 0.73 mmol) in CH2Cl2 (3 mL) at 0° C., then the mixture was stirred at 0° C. for 1 h. The mixture was then diluted with CH2Cl2, washed twice with sat. NaHCO3, and then water, then dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 0-5% methanolic ammonia in CH2Cl2 gave the title compound (68 mg, 36%) as a yellow solid; 1H NMR: (100° C.) 2.22 (6H, s), 2.40 (2H, t), 2.76 (3H, s), 2.98 (2H, t), 3.77 (3H, s), 3.90 (3H, s), 5.69 (1H, dd), 6.17 (1H, dd), 6.40 (1H, dd), 7.02-7.06 (2H, m), 7.21-7.25 (1H, m), 7.49 (1H, d), 8.23 (1H, d), 8.45 (1H, s), 8.47 (1H, s), 8.63 (1H, s), 8.86 (1H, s), 9.59 (1H, s); m/z: ES+ MH+ 525.32.

Workup

  1. washwashed twice with sat. NaHCO3
  2. dry with materialwater, then dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customPurification by FCC
  5. washeluting with 0-5% methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-bc31891eff654d889596a544ff2dc90b
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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