Cesium carbonate → HCID 71280137, 화합물

HRID 246308

반응식

HRID 246308 반응식
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:29])[F:28])[CH:24]=4)[NH:19][N:18]=3)[N:15]=2)[N:10]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:38]([O:42][C:43]([N:45]1[CH2:49][CH2:48][CH:47]([CH2:50]OS(C)(=O)=O)[CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:38]([O:42][C:43]([N:45]1[CH2:49][CH2:48][CH:47]([CH2:50][N:19]2[C:20]3[C:25](=[CH:24][C:23]([O:26][CH:27]([F:28])[F:29])=[CH:22][CH:21]=3)[C:17]([C:14]3[N:15]=[C:16]4[C:8]([C:6](=[O:7])[NH:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:9][N:10]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:11]4=[N:12][CH:13]=3)=[N:18]2)[CH2:46]1)=[O:44])([CH3:41])([CH3:39])[CH3:40]

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 4183641tert-Butyl 3-(((methylsulfonyl)oxy)methyl)pyrrolidine-1-carboxylateHCID 712795662-(5-difluoromethoxy-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

생성물 1

HCID 71280137HCID 71280137, 화합물수율 86%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
110 °C

실험 절차

A round-bottomed flask was charged with 2-(5-difluoromethoxy-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (120 mg, 0.23 mmol), 3-methanesulfonyloxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (crude from Step 1, 215 mg, 0.54 mmol), cesium carbonate (258 mg, 0.79 mmol) and DMF (1 ml). The reaction mixture was stirred at 110° C. for 1.5 h then cooled to room temperature, quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over 12 g silica gel with EtOAc/hexanes (gradient: 0-40% EtOAc). The appropriate fractions were combined and concentrated and the residue was triturated with petroleum ether to afford 138 mg (86%) of 3-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-ylmethyl}-pyrrolidine-1-carboxylic acid tert-butyl ester as a light yellow powder.

후처리

  1. temperaturethen cooled to room temperature
  2. customquenched with water
  3. extractionextracted with diethyl ether (2×)
  4. washThe combined organic layers were washed twice with water and once with brine
  5. dry with materialthen dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed over 12 g silica gel with EtOAc/hexanes (gradient: 0-40% EtOAc)
  9. concentrationconcentrated
  10. customthe residue was triturated with petroleum ether

출처 및 근거

ORD 기록
ord-be60d065c48b4cc3a84bf517c3a2c3ae
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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