Cesium carbonate → 4-({2-[4-(5-Chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoyl}amino)-2,6-difluorobenzoic acid

HRID 57067Notes

Reaction equation

HRID 57067 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([C:41]#[N:42])=[C:12]([C:14]2[C:19]([O:20][CH3:21])=[CH:18][N:17]([CH:22]([CH2:38][CH3:39])[C:23]([NH:25][C:26]3[CH:35]=[C:34]([F:36])[C:29]([C:30]([O:32]C)=[O:31])=[C:28]([F:37])[CH:27]=3)=[O:24])[C:16](=[O:40])[CH:15]=2)[CH:13]=1>CO.O>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([C:41]#[N:42])=[C:12]([C:14]2[C:19]([O:20][CH3:21])=[CH:18][N:17]([CH:22]([CH2:38][CH3:39])[C:23]([NH:25][C:26]3[CH:35]=[C:34]([F:36])[C:29]([C:30]([OH:32])=[O:31])=[C:28]([F:37])[CH:27]=3)=[O:24])[C:16](=[O:40])[CH:15]=2)[CH:13]=1

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 117622814Methyl 4-({2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoyl}amino)-2,6-difluorobenzoate

Product 1

HCID 1176229504-({2-[4-(5-Chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoyl}amino)-2,6-difluorobenzoic acid

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
60 °C

Procedure

67 mg (0.20 mmol, 2 eq.) of caesium carbonate were added to a solution of 53 mg (0.10 mmol) of methyl 4-({2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoyl}amino)-2,6-difluorobenzoate (racemate) in 1.25 ml of a mixture of methanol/water (4/1), and the resulting suspension was stirred at 60° C. for 1 h. Methanol was removed at 30° C. under reduced pressure. The reaction mixture was cooled to RT and adjusted to pH 3 using aqueous hydrochloric acid (1N). The aqueous phase was extracted with ethyl acetate. The combined organic phases were dried (sodium sulphate), filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC (water/acetonitrile/0.1% formic acid gradient). Yield: 11 mg (21% of theory)

Workup

  1. customMethanol was removed at 30° C. under reduced pressure
  2. temperatureThe reaction mixture was cooled to RT
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. dry with materialThe combined organic phases were dried (sodium sulphate)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by preparative HPLC (water/acetonitrile/0.1% formic acid gradient)

Sources & evidence

ORD record
ord-14e2f094765d4adf9fff67529458f8aa
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Reaction notes

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