Cesium carbonate → 1-(4-Cyano-benzyl)-6-methyl-4-oxo-5-(3-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid

HRID 527339

Reaction equation

Br[C:2]1[C:3](=[O:21])[C:4]([C:18]([OH:20])=[O:19])=[CH:5][N:6]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=2)[C:7]=1[CH3:8].[F:22][C:23]([F:34])([F:33])[C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1>[C:16]([C:13]1[CH:14]=[CH:15][C:10]([CH2:9][N:6]2[C:7]([CH3:8])=[C:2]([C:28]3[CH:27]=[CH:26][CH:25]=[C:24]([C:23]([F:34])([F:33])[F:22])[CH:29]=3)[C:3](=[O:21])[C:4]([C:18]([OH:20])=[O:19])=[CH:5]2)=[CH:11][CH:12]=1)#[N:17]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 5-bromo-1-(4-cyano-benzyl)-6-methyl-4-oxo-1,4-dihydro-pyridine-3-carboxylic acid (preparation 5b, 2.55 g, 7.34 mmol), 3-(trifluoromethyl)phenylboronic acid (1.65 g, 8.69 mmol), 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (340 mg, 0.47 mmol) and Cs2CO3 (4.20 g, 12.9 mmol) in dioxane (20.0 mL) is heated for 72 h at 80° C. The reaction mixture is filtered over silica and the filtrate is concentrated under reduced pressure and purified by preparative reversed phase HPLC (first purification: Sunfire, gradient of methanol in water, 0.1% TFA; second purification: Xbridge, gradient of methanol in water, 0.1% NH4OH, 60° C.). Yield: 514 mg (17% of theory); ESI mass spectrum: [M+H]+=413; r.t. HPLC: 1.37 min (Z002_005).

Workup

filtrationThe reaction mixture is filtered over silica
concentrationthe filtrate is concentrated under reduced pressure
custompurified by preparative reversed phase HPLC (first purification: Sunfire, gradient of methanol in water, 0.1% TFA; second purification: Xbridge, gradient of methanol in water, 0.1% NH4OH, 60° C.)
customr.t
custom1.37 min (Z002_005)

Sources & evidence

ORD record: ord-b48c2db1718e485bb43ef499c6fe94ac
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346794B1

Linked notes

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