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

HRID 1842635
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HRID 1842635 반응식
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[Cl:6][C:7]1[C:8]([C:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:32]([CH3:39])[CH:31]=2)=[N:9][C:10]([NH:13][C:14]2[CH:15]=[C:16]([NH2:29])[C:17]([N:22]([CH2:24][CH2:25][N:26]([CH3:28])[CH3:27])[CH3:23])=[CH:18][C:19]=2[O:20][CH3:21])=[N:11][CH:12]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:6][C:7]1[C:8]([C:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:32]([CH3:39])[CH:31]=2)=[N:9][C:10]([NH:13][C:14]2[C:19]([O:20][CH3:21])=[CH:18][C:17]([N:22]([CH2:24][CH2:25][N:26]([CH3:27])[CH3:28])[CH3:23])=[C:16]([NH:29][C:1](=[O:4])[CH:2]=[CH2:3])[CH:15]=2)=[N:11][CH:12]=1
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참가 물질

5

반응물 3

HCID 13140Acryloyl chloride2회HCID 81531DiisopropylethylamineHCID 86677266N4-[5-Chloro-4-(1-methylindol-3-yl)pyrimidin-2-yl]-N1-(2-dimethylaminoethyl)-5-methoxy-N1-methylbenzene-1,2,4-triamine2회

생성물 1

HCID 86677265N-(5-{[5-Chloro-4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}-2-{2-dimethylaminoethyl-methylamino}-4-methoxyphenyl)prop-2-enamide수율 77%

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

실험 절차

A solution of acryloyl chloride (0.026 mL, 0.32 mmol) in CH2Cl2 (1 mL) was added to a mixture of N4-[5-chloro-4-(1-methylindol-3-yl)pyrimidin-2-yl]-N1-(2-dimethylamino-ethyl)-5-methoxy-N1-methylbenzene-1,2,4-triamine (Intermediate 97, 130 mg, 0.27 mmol) and DIPEA (0.090 mL, 0.54 mmol) in CH2Cl2 (2 mL) at 0° C. The mixture was stirred at 0° C. for 2.5 h (during this time a further 0.2 eq acryloyl chloride was added). The mixture was then diluted with CH2Cl2, washed twice with sat. NaHCO3 and then with water, dried (MgSO4), and concentrated in vacuo. Purification by FCC, eluting with 0-5% methanolic ammonia in CH2Cl2 gave the title compound (111 mg, 77%) as a yellow solid; 1H NMR: (CDCl3) 2.26 (6H, s), 2.23-2.33 (2H, m), 2.70 (3H, s), 2.86-2.89 (2H, m), 3.88 (3H, s), 3.91 (3H, s), 5.67 (1H, d), 6.25-6.44 (2H, m), 6.79 (1H, s), 7.20-7.37 (3H, m), 7.57 (1H, s), 8.36-8.45 (3H, m), 9.54 (1H, s), 10.11 (1H, s); m/z: ES+ MH+ 534, 536.

후처리

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

출처 및 근거

ORD 기록
ord-9918b1b20747414e9430964be09f5366
출처 데이터셋
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08946235B2

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