Water → HCID 59249370, compound

HRID 1807248Notes

Reaction equation

HRID 1807248 reaction equation
I[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([NH:9][C:10]([CH:12]2[CH:16]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=3[F:24])[C:15]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=3[F:34])([C:25]#[N:26])[CH:14]([CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[NH:13]2)=[O:11])=[C:4]([CH3:40])[CH:3]=1.O.[C:42](=O)([O-:44])[O-:43].[K+].[K+].[C]=O>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([C@@:15]2([C:25]#[N:26])[C@H:14]([CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[NH:13][C@@H:12]([C:10]([NH:9][C:5]3[C:4]([CH3:40])=[CH:3][C:2]([C:42]([OH:44])=[O:43])=[C:7]([CH3:8])[CH:6]=3)=[O:11])[C@@H:16]2[C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=2[F:24])=[C:28]([F:34])[CH:29]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 72243917HCID 72243917, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 59249370HCID 59249370, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of rac (2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (4-iodo-2,5-dimethyl-phenyl)-amide (Example 365, 149 mg, 0.214 mmol) in DMF (5 ml) was added water (0.2 ml), and potassium carbonate (60 mg, 0.428 mmol). The mixture was bubbled with nitrogen and palladium acetate (5 mg, 0.021 mmol) was added. The mixture was subjected to carbon monoxide atmosphere at 50 psi and was heated at 70° C. for 3 h. The mixture was then filtered through celite, acidified with HOAc and extracted with EtOAc (3×10 ml). The organic solution was concentrated and was purified by reverse phase HPLC using acetonitrile and water. Obtained the title compound as a white powder, (45 mg, 35% yield).

Workup

  1. additionwas added
  2. filtrationThe mixture was then filtered through celite
  3. extractionextracted with EtOAc (3×10 ml)
  4. concentrationThe organic solution was concentrated
  5. customwas purified by reverse phase

Sources & evidence

ORD record
ord-70535faa019e4aef9d57602106a0b0af
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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