Sodium Bicarbonate → Ethyl 4-[4-chloro-2-{[6-(dimethylamino)-4-methylpyridin-3-yl]amino}-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate

HRID 1628411ノート

反応式

HRID 1628411 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][N:26]([CH3:35])[C:27]1[CH:32]=[C:31]([CH3:33])[C:30]([NH2:34])=[CH:29][N:28]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>CN1CCCC1=O>[Cl:19][C:18]1[C:4]2[N:3]=[C:2]([NH:34][C:30]3[CH:29]=[N:28][C:27]([N:26]([CH3:25])[CH3:35])=[CH:32][C:31]=3[CH3:33])[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 4

HCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 22136281N2,N2,4-trimethylpyridine-2,5-diamineHCID 68761768Ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate

生成物 1

HCID 68772671Ethyl 4-[4-chloro-2-{[6-(dimethylamino)-4-methylpyridin-3-yl]amino}-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate収率 43.1%

試薬・触媒・溶媒 1

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; 472 mg, 1.27 mmol), N2,N2,4-trimethylpyridine-2,5-diamine (580 mg, 3.81 mmol) and p-toluenesulfonic acid monohydrate (241 mg, 1.27 mmol) in 1-methyl-2-pyrrolidinone (4 mL) was irradiated by microwave at 180° C. for 135 min. After cooling, aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. Organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 20-80% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give a solid, which was recrystallized from ethyl acetate/n-hexane to give the title compound (266 mg, 0.547 mmol, 43%) as a colorless solid.

後処理

  1. customwas irradiated by microwave at 180° C. for 135 min
  2. temperatureAfter cooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. washOrganic layer was washed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel eluting with a 20-80% ethyl acetate/n-hexane gradient mixture
  8. concentrationThe filtrate was concentrated in vacuo
  9. customto give a solid, which
  10. customwas recrystallized from ethyl acetate/n-hexane

出典と根拠

ORDレコード
ord-327beb27800d4d4fa39ff9e87edc748e
出典データセット
uspto-grants-2014_07
特許番号
US08785460B2

反応ノート

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