1,3,5-trimethyl-1H-pyrazol-4-amine → Ethyl 4-{4-chloro-7-(1-ethylpropyl)-2-[(1,3,5-trimethyl-1H-pyrazol-4-yl)amino]-1H-benzimidazol-1-yl}butanoate

HRID 1398762노트

반응식

HRID 1398762 반응식
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.[NH2:25][C:26]1[C:27]([CH3:33])=[N:28][N:29]([CH3:32])[C:30]=1[CH3:31].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:25][C:26]3[C:27]([CH3:33])=[N:28][N:29]([CH3:32])[C:30]=3[CH3:31])[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

참가 물질

6

반응물 4

HCID 1616031,3,5-trimethyl-1H-pyrazol-4-amineHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 68761768Ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate

생성물 1

HCID 68773743Ethyl 4-{4-chloro-7-(1-ethylpropyl)-2-[(1,3,5-trimethyl-1H-pyrazol-4-yl)amino]-1H-benzimidazol-1-yl}butanoate수율 74%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

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온도
150 °C

실험 절차

A mixture of ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate (Reference Example 33; 371 mg, 1.00 mmol), 4-amino-1,3,5-trimethylpyrazole (375 mg, 3.00 mmol) and p-toluenesulfonic acid monohydrate (190 mg, 1.00 mmol) in 1-methyl-2-pyrrolidinone (3 mL) was stirred at 150° C. for 16 hr. 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 0-5% methanol/ethyl acetate gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethyl acetate/n-hexane to give the title compound (340 mg, 0.74 mmol, 74%) as a colorless solid.

후처리

  1. temperatureAfter cooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washOrganic layer was washed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel eluting with a 0-5% methanol/ethyl acetate gradient mixture
  7. concentrationThe filtrate was concentrated in vacuo
  8. customto give the solid, which
  9. customwas recrystallized from ethyl acetate/n-hexane

출처 및 근거

ORD 기록
ord-3cf6f31fdc5b4d71a9b008fd79de7e37
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901141B2

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