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

HRID 1842628ノート

反応式

HRID 1842628 の反応式
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[CH3:6][O:7][C:8]1[CH:13]=[C:12]([N:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]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)[C:26]([CH3:39])=[CH:25][N:24]=1.CCN(C(C)C)C(C)C>C1COCC1.O.C(Cl)Cl.C(OCC)C>[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)[C:26]([CH3:39])=[CH:25][N:24]=2)=[CH:10][C:11]([NH:21][C:1](=[O:4])[CH:2]=[CH2:3])=[C:12]([N:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)[CH:13]=1

参加物

8

反応物 3

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 866772524-methoxy-N'-[5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-yl]-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine2 回

生成物 1

HCID 86677251N-(4-Methoxy-5-{[5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}-2-{4-methylpiperazin-1-yl}phenyl)prop-2-enamide収率 52.1%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

Acryloyl chloride (0.358 mL, 1M in THF, 0.36 mmol) was added dropwise to a mixture of 4-methoxy-N′-[5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-yl]-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine (Intermediate 77, 164 mg, 0.36 mmol) and DIPEA (0.069 mL, 0.39 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. The organic solution was then dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 1-8% 7M methanolic ammonia in CH2Cl2 gave a pale yellow dry film after concentration of the appropriate fractions in vacuo. This material was dissolved in CH2Cl2 and the resulting solution was diluted with diethyl ether, which resulted in a beige solid precipitating from the solution. This solid was collected by filtration, washed with diethyl ether and then dried to give the title compound (96 mg, 52%); 1H NMR: 2.26 (3H, s), 2.37 (3H, s), 2.51 (4H, s), 2.87 (4H, s), 3.83 (3H, s), 3.89 (3H, s), 5.70 (1H, d), 6.17 (1H, d), 6.60 (1H, dd), 6.86 (1H, s), 7.09 (1H, t), 7.22 (1H, t), 7.48 (1H, d), 7.87 (1H, s), 8.05 (1H, s), 8.21 (1H, s), 8.37 (1H, d), 8.46 (1H, s), 9.00 (1H, s); m/z: ES+ MH+ 512.46.

後処理

  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 materialThe organic solution was then dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customPurification by FCC
  8. washeluting with 1-8% 7M methanolic ammonia in CH2Cl2
  9. customgave a pale yellow dry film after concentration of the appropriate fractions in vacuo
  10. customresulted in a beige solid
  11. customprecipitating from the solution
  12. filtrationThis solid was collected by filtration
  13. washwashed with diethyl ether
  14. customdried

出典と根拠

ORDレコード
ord-e2f48dc0510646abaa2bc4dc91c4c330
出典データセット
uspto-grants-2015_02
特許番号
US08946235B2

反応ノート

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