Potassium Carbonate → 1-[1-(4-Cyano-phenyl)-ethyl]-5-(3-difluoromethyl-phenyl)-6-methyl-4-oxo-1,4-dihydro-pyridine-3-carboxylic acid methylamide

HRID 512503

Reaction equation

[CH3:1][NH:2][C:3]([C:5]1[C:10](=[O:11])[C:9](Br)=[C:8]([CH3:13])[N:7]([CH:14]([C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=2)[CH3:15])[CH:6]=1)=[O:4].[F:24][CH:25]([F:35])[C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1.C([O-])([O-])=O.[K+].[K+]>C(#N)C.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][NH:2][C:3]([C:5]1[C:10](=[O:11])[C:9]([C:30]2[CH:29]=[CH:28][CH:27]=[C:26]([CH:25]([F:35])[F:24])[CH:31]=2)=[C:8]([CH3:13])[N:7]([CH:14]([C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=2)[CH3:15])[CH:6]=1)=[O:4]

Participants

Conditions

Temperature: 75 °C

Procedure

To a solution of 5-bromo-1-[1-(4-cyano-phenyl)-ethyl]-6-methyl-4-oxo-1,4-dihydro-pyridine-3-carboxylic acid methylamide (preparation 9, 100 mg, 0.267 mmol), 3-difluoromethyl-phenylboronic acid (67 mg, 0.390 mmol), palladium (0) tetrakis(triphenylphosphine) (25 mg, 0.022 mmol) in acetonitrile (2 mL) is added 2 M aqueous K2CO3 solution (0.30 mL, 0.60 mmol). After stirring for 18 h at 75° C., the reaction mixture is purified by preparative reversed-phase HPLC (XBridge, gradient of methanol in water, 0.1% NH4OH, 60° C.). Yield: 80 mg (71% of theory); ESI mass spectrum: [M+H]+=422; Retention time HPLC: 0.99 min (Z018_S04).

Workup

customthe reaction mixture is purified by preparative reversed-phase HPLC (XBridge, gradient of methanol in water, 0.1% NH4OH, 60° C.)
custom0.99 min (Z018_S04)

Sources & evidence

ORD record: ord-d4e8b9451ee44f71b9245682c59a86ec
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102624B2

Linked notes

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