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

HRID 57017Notes

Reaction equation

HRID 57017 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:36]#[N:37])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:31][CH:32]([F:34])[F:33])[C:17]([NH:19][C:20]3[CH:30]=[CH:29][C:23]([C:24]([O:26]CC)=[O:25])=[CH:22][CH:21]=3)=[O:18])[C:10](=[O:35])[CH:9]=2)[CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CO.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:36]#[N:37])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:31][CH:32]([F:34])[F:33])[C:17]([NH:19][C:20]3[CH:30]=[CH:29][C:23]([C:24]([OH:26])=[O:25])=[CH:22][CH:21]=3)=[O:18])[C:10](=[O:35])[CH:9]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 117622837Ethyl 4-({2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-4,4-difluorobutanoyl}amino)benzoate

Product 1

HCID 1176229334-({2-[4-(5-Chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-4,4-difluorobutanoyl}amino)benzoic acid

Reagents, catalysts & solvents 1

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

Procedure

80 mg (151 μmol) of ethyl 4-({2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-4,4-difluorobutanoyl}amino)benzoate (racemate) in 2 ml of methanol/water (4/1) were reacted with 326 mg (302 μmol) of caesium carbonate according to General Method 4. The crude product was purified by preparative HPLC [column: Chromatorex C18, 10 μm, 125 mm×30 mm, mobile phase: acetonitrile/0.05% formic acid gradient (0 to 3 min 10% acetonitrile, to 35 min 90% acetonitrile and a further 3 min 90% acetonitrile)]. Yield: 18 mg (23% of theory)

Workup

  1. customThe crude product was purified by preparative HPLC [column
  2. customa further 3 min 90% acetonitrile

Sources & evidence

ORD record
ord-b7b8280dafc64f5596a5512384a17ed4
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Reaction notes

Loading…