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Cesium carbonate → 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

HRID 246308
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 246308
[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]
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Komponenten

5

Edukt 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

Produkt 1

HCID 712801373-{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
Ausbeute 86 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-be60d065c48b4cc3a84bf517c3a2c3ae
Quelldatensatz
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08658646B2

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