p-Toluenesulfonic acid monohydrate → Ethyl 4-{4-chloro-7-(1-ethylpropyl)-2-[(4-methyl-6-pyrrolidin-1-ylpyridin-3-yl)amino]-1H-benzimidazol-1-yl}butanoate

HRID 1398772ノート

反応式

HRID 1398772 の反応式
Cl[C:2]1[N:6]([CH2:7][CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]2[C:15]([CH:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[CH:16][CH:17]=[C:18]([Cl:19])[C:4]=2[N:3]=1.[CH3:25][C:26]1[CH:31]=[C:30]([N:32]2[CH2:36][CH2:35][CH2:34][CH2:33]2)[N:29]=[CH:28][C:27]=1[NH2:37].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN1CCCC1=O.C(OCC)(=O)C>[Cl:19][C:18]1[C:4]2[N:3]=[C:2]([NH:37][C:27]3[CH:28]=[N:29][C:30]([N:32]4[CH2:33][CH2:34][CH2:35][CH2:36]4)=[CH:31][C:26]=3[CH3:25])[N:6]([CH2:7][CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]=2[C:15]([CH:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[CH:16][CH:17]=1

参加物

6

反応物 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 669079634-Methyl-6-pyrrolidin-1-ylpyridin-3-amineHCID 68761768Ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate

生成物 1

HCID 68761864Ethyl 4-{4-chloro-7-(1-ethylpropyl)-2-[(4-methyl-6-pyrrolidin-1-ylpyridin-3-yl)amino]-1H-benzimidazol-1-yl}butanoate収率 36.1%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

A mixture of ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate (Reference Example 33; 1.50 g, 4.04 mmol), 4-methyl-6-pyrrolidin-1-ylpyridin-3-amine (1.44 g, 8.09 mmol) and p-toluenesulfonic acid monohydrate (695 mg, 4.04 mmol) in 1-methyl-2-pyrrolidinone (8 mL) was irradiated by microwave at 180° C. for 110 min. After cooling, the mixture was diluted with ethyl acetate, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 20-100% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give a solid, which was recrystallized from ethyl acetate/isopropyl ether to give the title compound (745 mg, 1.46 mmol, 36%) as a colorless solid.

後処理

  1. customwas irradiated by microwave at 180° C. for 110 min
  2. temperatureAfter cooling
  3. washwashed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel eluting with a 20-100% ethyl acetate/n-hexane gradient mixture
  7. concentrationThe filtrate was concentrated in vacuo
  8. customto give a solid, which
  9. customwas recrystallized from ethyl acetate/isopropyl ether

出典と根拠

ORDレコード
ord-3b0428f289e24c80811e286854fd0cf8
出典データセット
uspto-grants-2014_12
特許番号
US08901141B2

反応ノート

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