Triethylamine → N-{4-Methoxy-2-[1-methyl-3,6-dihydro-2H-pyridin-4-yl]-5-[(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]phenyl}prop-2-enamide

HRID 1842659ノート

反応式

HRID 1842659 の反応式
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[CH3:6][O:7][C:8]1[CH:13]=[C:12]([C:14]2[CH2:15][CH2:16][N:17]([CH3:20])[CH2:18][CH:19]=2)[C:11]([NH2:21])=[CH:10][C:9]=1[NH:22][C:23]1[N:28]=[C:27]([C:29]2[CH:30]=[N:31][N:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=23)[CH:26]=[CH:25][N:24]=1.C(N(CC)CC)C>C1COCC1>[CH3:6][O:7][C:8]1[C:9]([NH:22][C:23]2[N:28]=[C:27]([C:29]3[CH:30]=[N:31][N:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=34)[CH:26]=[CH:25][N:24]=2)=[CH:10][C:11]([NH:21][C:1](=[O:4])[CH:2]=[CH2:3])=[C:12]([C:14]2[CH2:15][CH2:16][N:17]([CH3:20])[CH2:18][CH:19]=2)[CH:13]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 13140Acryloyl chloride2 回HCID 866773074-methoxy-6-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-N'-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamine2 回

生成物 1

HCID 86677306N-{4-Methoxy-2-[1-methyl-3,6-dihydro-2H-pyridin-4-yl]-5-[(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]phenyl}prop-2-enamide収率 25.8%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

A solution of acryloyl chloride (20 μL, 0.25 mmol) was added dropwise to 4-methoxy-6-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-N′-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamine (Intermediate 150, 180 mg, 0.42 mmol) and triethylamine (73 lilt, 0.53 mmol) in THF (3 mL) at −5° C. over a period of 1 minute under an atmosphere of N2. The resulting mixture was stirred at 0° C. for 0.25 h. The reaction was judged to be incomplete so further acryloyl chloride (10 μL, 0.125 mmol) was added dropwise and the mixture was stirred at 0° C. for a further 15 minutes. The mixture was then concentrated in vacuo and the resulting residue was dissolved in CH2Cl2 (5 mL) plus a few drops of CH3OH. This solution was washed with sat. NaHCO3 (2 mL), dried (MgSO4) and filtered through a 1 g silica pad, eluting with 4:1 CH2Cl2—CH3OH. Eluent that contained desired product was concentrated in vacuo. Purification by FCC, eluting with 5-20% CH3OH in CH2Cl2 gave the title compound (31 mg, 14%) as a cream crystalline solid; 1H NMR: 2.33 (3H, s), 2.40 (2H, s), 2.57 (2H, d), 3.03 (2H, s), 3.89 (3H, s), 5.70 (2H, m), 6.17 (1H, m), 6.46 (1H, m), 6.88 (1H, s), 7.09 (1H, t), 7.32 (1H, d), 7.47 (1H, t), 8.12 (1H, s), 8.21 (1H, s), 8.39 (1H, d), 8.51 (1H, d), 8.81 (2H, m), 9.36 (1H, s); m/z: ES+ MH+ 482.

後処理

  1. additionwas added dropwise
  2. stirringthe mixture was stirred at 0° C. for a further 15 minutes
  3. concentrationThe mixture was then concentrated in vacuo
  4. dissolutionthe resulting residue was dissolved in CH2Cl2 (5 mL)
  5. washThis solution was washed with sat. NaHCO3 (2 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered through a 1 g silica pad
  8. washeluting with 4:1 CH2Cl2—CH3OH
  9. concentrationwas concentrated in vacuo
  10. customPurification by FCC
  11. washeluting with 5-20% CH3OH in CH2Cl2

出典と根拠

ORDレコード
ord-4a18788b334540fa97f35a5e0276be08
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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