Cesium carbonate → 4-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-yl}-butyric acid methyl ester

HRID 246300

Reaktionsgleichung

Reaktionsgleichung von HRID 246300
[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].Br[CH2:39][CH2:40][CH2:41][C:42]([O:44][CH3:45])=[O:43].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH3:45][O:44][C:42](=[O:43])[CH2:41][CH2:40][CH2:39][N:19]1[C:20]2[C:25](=[CH:24][C:23]([O:26][CH:27]([F:28])[F:29])=[CH:22][CH:21]=2)[C:17]([C:14]2[N:15]=[C:16]3[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]3=[N:12][CH:13]=2)=[N:18]1

Komponenten

5

Edukt 3

HCID 10796Cesium carbonateHCID 107604Methyl 4-bromobutyrateHCID 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 712796884-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-yl}-butyric acid methyl esterAusbeute 83 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A microwave vial 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 (100 mg, 0.19 mmol), methyl 4-bromobutanoate (69 mg, 0.38 mmol), cesium carbonate (184 mg, 0.57 mmol) and DMF (0.85 ml). The vial was flushed with argon, sealed and heated in a microwave reactor at 100° C. for 2 h. The reaction was 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: 0-30% EtOAc) to afford 99 mg (83%) of 4-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-yl}-butyric acid methyl ester as a light yellow solid.

Aufarbeitung

  1. customThe vial was flushed with argon
  2. customsealed
  3. customThe reaction was quenched with water
  4. extractionextracted with diethyl ether (2×)
  5. washThe combined organic layers were washed twice with water and once with brine
  6. dry with materialthen dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed over 12 g silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-318870b305cb4be8be1542b04b8d191f
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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