Potassium Carbonate → 1-Cyclobutyl-6-methyl-4-oxo-5-(3-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid (5-methyl-[1,3,4]oxadiazol-2-ylmethyl)-amide

HRID 524346Notes

Reaction equation

[CH3:1][C:2]1[O:6][C:5]([CH2:7][NH:8][C:9]([C:11]2[C:16](=[O:17])[C:15](Br)=[C:14]([CH3:19])[N:13]([CH:20]3[CH2:23][CH2:22][CH2:21]3)[CH:12]=2)=[O:10])=[N:4][N:3]=1.[F:24][C:25]([F:36])([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>[CH3:1][C:2]1[O:6][C:5]([CH2:7][NH:8][C:9]([C:11]2[C:16](=[O:17])[C:15]([C:30]3[CH:29]=[CH:28][CH:27]=[C:26]([C:25]([F:36])([F:35])[F:24])[CH:31]=3)=[C:14]([CH3:19])[N:13]([CH:20]3[CH2:23][CH2:22][CH2:21]3)[CH:12]=2)=[O:10])=[N:4][N:3]=1

Participants

Conditions

Temperature: 75 °C

Procedure

To a solution of 5-bromo-1-cyclobutyl-6-methyl-4-oxo-1,4-dihydro-pyridine-3-carboxylic acid (5-methyl-[1,3,4]oxadiazol-2-ylmethyl)-amide (preparation 24, 44 mg, 0.115 mmol), 3-(trifluoromethyl)phenyl-boronic acid (26 mg, 0.137 mmol), 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (13 mg, 0.018 mmol) in acetonitrile (0.5 mL) is added 2 M aqueous K2CO3 solution (0.10 mL, 0.20 mmol). After stirring for 18 h at 75° C., the reaction mixture is filtered and purified by preparative reversed-phase HPLC (XBridge, gradient of methanol in water, 0.3% NH4OH, 60° C.). Yield: 40 mg (78% of theory); ESI mass spectrum: [M+H]+=447; Retention time HPLC: 1.09 min (Z003_001).

Workup

filtrationthe reaction mixture is filtered
custompurified by preparative reversed-phase HPLC (XBridge, gradient of methanol in water, 0.3% NH4OH, 60° C.)
custom1.09 min (Z003_001)

Sources & evidence

ORD record: ord-ee1ac6f8f1384a259a350ca5ca36cdf2
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340507B2

Reaction notes

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