Acetic Acid → 1-[1-(4-Cyano-phenyl)-ethyl]-5-(3-difluoromethyl-phenyl)-6-methyl-4-oxo-1,4-dihydro-pyridine-3-carboxylic acid 4-methanesulfonyl-benzylamide

HRID 512506Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 512506
[CH3:1][S:2]([C:5]1[CH:33]=[CH:32][C:8]([CH2:9][NH:10][C:11]([C:13]2[C:18](=[O:19])[C:17](Br)=[C:16]([CH3:21])[N:15]([CH:22]([C:24]3[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[CH:26][CH:25]=3)[CH3:23])[CH:14]=2)=[O:12])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[F:34][CH:35]([F:45])[C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[CH:40][CH:41]=1.C([O-])([O-])=O.[K+].[K+].C(O)(=O)C>C(#N)C.CO.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH3:1][S:2]([C:5]1[CH:33]=[CH:32][C:8]([CH2:9][NH:10][C:11]([C:13]2[C:18](=[O:19])[C:17]([C:40]3[CH:39]=[CH:38][CH:37]=[C:36]([CH:35]([F:45])[F:34])[CH:41]=3)=[C:16]([CH3:21])[N:15]([CH:22]([C:24]3[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[CH:26][CH:25]=3)[CH3:23])[CH:14]=2)=[O:12])=[CH:7][CH:6]=1)(=[O:4])=[O:3]

Komponenten

8

Edukt 4

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 447172443-Difluoromethyl-phenylboronic acidHCID 867115385-Bromo-1-[1-(4-cyano-phenyl)-ethyl]-6-methyl-4-oxo-1,4-dihydro-pyridine-3-carboxylic acid 4-methanesulfonyl-benzylamide

Produkt 1

HCID 867115451-[1-(4-Cyano-phenyl)-ethyl]-5-(3-difluoromethyl-phenyl)-6-methyl-4-oxo-1,4-dihydro-pyridine-3-carboxylic acid 4-methanesulfonyl-benzylamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 887MethanolLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

To a solution of 5-bromo-1-[1-(4-cyano-phenyl)-ethyl]-6-methyl-4-oxo-1,4-dihydro-pyridine-3-carboxylic acid 4-methanesulfonyl-benzylamide (preparation 11, 110 mg, 0.208 mmol), 3-difluoromethyl-phenylboronic acid (48 mg, 0.28 mmol), palladium (0) tetrakis(triphenylphosphine) (32 mg, 0.028 mmol) in acetonitrile (2 mL) is added 2 M aqueous K2CO3 solution (0.21 mL, 0.42 mmol). After stirring for 18 h at 75° C., the reaction mixture is diluted with methanol, acidified with acetic acid and purified by preparative reversed-phase HPLC (XBridge, gradient of methanol in water, 0.1% TFA, 60° C.). Yield: 90 mg (75% of theory); ESI mass spectrum: [M+H]+=576; Retention time HPLC: 1.03 min (Z018_S04).

Aufarbeitung

  1. custompurified by preparative reversed-phase HPLC (XBridge, gradient of methanol in water, 0.1% TFA, 60° C.)
  2. custom1.03 min (Z018_S04)

Quellen und Nachweise

ORD-Eintrag
ord-fb722ff12abe431c974846d485b0830d
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09102624B2

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