N-methyl-2-pyrrolidone → N-[6-(azetidin-1-yl)-3-pyridinyl]-3-dimethylsilyl-5-ethyl-1-[(3-fluorophenyl)methyl]indole-2-carboxamide

HRID 1948793

Reaktionsgleichung

Reaktionsgleichung von HRID 1948793
C([SiH:3]([CH3:5])[CH3:4])C.[N:6]1([C:10]2[N:15]=[CH:14][C:13]([NH:16][C:17]([C:19]3[N:20]([CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=4)[C:21]4[C:26]([CH:27]=3)=[CH:25][C:24](I)=[CH:23][CH:22]=4)=[O:18])=[CH:12][CH:11]=2)[CH2:9][CH2:8][CH2:7]1.[O-]P(OP(OP([O-])([O-])=O)([O-])=O)(=O)[O-].[K+].[K+].[K+].[K+].[K+].CN1CC[CH2:58][C:57]1=O>O.CCOCC.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[N:6]1([C:10]2[N:15]=[CH:14][C:13]([NH:16][C:17]([C:19]3[N:20]([CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=4)[C:21]4[C:26]([C:27]=3[SiH:3]([CH3:5])[CH3:4])=[CH:25][C:24]([CH2:57][CH3:58])=[CH:23][CH:22]=4)=[O:18])=[CH:12][CH:11]=2)[CH2:9][CH2:8][CH2:7]1

Komponenten

8

Edukt 4

HCID 13387N-methyl-2-pyrrolidoneHCID 61695Pentapotassium TriphosphateHCID 69795EthyldimethylsilaneHCID 66850402HCID 66850402, Verbindung

Produkt 1

HCID 131730342N-[6-(azetidin-1-yl)-3-pyridinyl]-3-dimethylsilyl-5-ethyl-1-[(3-fluorophenyl)methyl]indole-2-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418851HCID 178418851, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 3283Diethyl EtherLösungsmittel

Versuchsvorschrift

27 mg (0.31 mmol) of (ethyl)dimethylsilane and 15 mg (0.03 mmol) of bis(tri-tert-butylphosphine)palladium are added to a suspension of 0.15 g (0.28 mmol) of N-[6-(azetidin-1-yl)pyridin-3-yl]-5-iodo-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxamide, prepared according to the protocol described in stage 8.3, and of 0.18 g (0.85 mmol) of potassium triphosphate in 2 ml of dry 1-methyl-2-pyrrolidinone (NMP), maintained under an inert atmosphere. The reaction mixture is then stirred at ambient temperature under an inert atmosphere for 6 h and then diluted with 40 ml of a mixture of water and ethyl acetate (1/1). The resulting mixture is separated by settling out and the aqueous phase is extracted with 2×10 ml of ethyl acetate. The combined organic phases are dried over sodium sulphate, filtered and concentrated under reduced pressure. The resulting oil is purified by silica gel column chromatography, elution being carried out with a mixture of heptane and ethyl acetate. 108 mg of the expected product are isolated.

Aufarbeitung

  1. customprepared
  2. customThe resulting mixture is separated
  3. extractionthe aqueous phase is extracted with 2×10 ml of ethyl acetate
  4. dry with materialThe combined organic phases are dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting oil is purified by silica gel column chromatography, elution
  8. additionbeing carried out with a mixture of heptane and ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-af3f5861fc144a92849245965d92a664
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399491B2

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