Sodium hydride → 3,5-dimethyl-1-pyrazin-2-yl-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1865306노트

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HRID 1865306 반응식
[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:12])=[N:8][NH:9][C:10]=1[CH3:11])=[O:5])[CH3:2].[H-].[Na+].[H][H].Cl[C:18]1[CH:23]=[N:22][CH:21]=[CH:20][N:19]=1>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:12])=[N:8][N:9]([C:18]2[CH:23]=[N:22][CH:21]=[CH:20][N:19]=2)[C:10]=1[CH3:11])=[O:5])[CH3:2]

참가 물질

6

반응물 4

HCID 24758Sodium hydrideHCID 73277ChloropyrazineHCID 215436ethyl 3,5-dimethyl-1H-pyrazole-4-carboxylateHCID 178418361HCID 178418361, 화합물

생성물 1

HCID 685753573,5-dimethyl-1-pyrazin-2-yl-1H-pyrazole-4-carboxylic acid ethyl ester수율 44%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

step 1—To a solution of 3,5-dimethyl-1H-pyrazole-4-carboxylic acid ethyl ester (1 g, 5.95 mmol) in DMF (20 mL) cooled to 0° C. was added portionwise NaH (60% in mineral oil, 171 mg, 7.13 mmol). After hydrogen evolution ceased, 2-chloro-pyrazine (0.64 mL, 7.13 mmol) was added and the reaction was stirred at 50° C. for 24 h. The reaction mixture was cooled to RT, partitioned between EtOAc and saturated NH4Cl. The aqueous layer was extracted twice with EtOAc. The combined organic layers were dried (Na2SO4), filtered and evaporated. The residue was purified via SiO2 chromatography eluting with hexane/EtOAc to afford 0.64 g (44%) of 3,5-dimethyl-1-pyrazin-2-yl-1H-pyrazole-4-carboxylic acid ethyl ester (124a). The ethyl ester was hydrolyzed to the corresponding acid with KOH in aqueous EtOH as described in step 2 of example 31.

후처리

  1. temperatureThe reaction mixture was cooled to RT
  2. custompartitioned between EtOAc and saturated NH4Cl
  3. extractionThe aqueous layer was extracted twice with EtOAc
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified via SiO2 chromatography
  8. washeluting with hexane/EtOAc

출처 및 근거

ORD 기록
ord-268eb24ec63f4dcf860b80cc557966a6
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07625905B2

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