Methanol → Methyl 4-chloro-3-(3-{[5-cyano-2-propyl-4-(trifluoromethyl)-1H-indol-1-yl]methyl}-1,2,4-oxadiazol-5-yl)benzoate

HRID 913678Notes

Reaction equation

HRID 913678 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[C:9]1[O:13][N:12]=[C:11]([CH2:14][N:15]2[C:23]3[C:18](=[C:19]([C:26]([F:29])([F:28])[F:27])[C:20]([C:24]#[N:25])=[CH:21][CH:22]=3)[CH:17]=[C:16]2[CH2:30][CH2:31][CH3:32])[N:10]=1.[CH3:33][OH:34].CN([CH:38]=[O:39])C>CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:33]([O:39][CH3:38])=[O:34])=[CH:4][C:3]=1[C:9]1[O:13][N:12]=[C:11]([CH2:14][N:15]2[C:23]3[C:18](=[C:19]([C:26]([F:28])([F:29])[F:27])[C:20]([C:24]#[N:25])=[CH:21][CH:22]=3)[CH:17]=[C:16]2[CH2:30][CH2:31][CH3:32])[N:10]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 6228DimethylformamideHCID 578001721-{[5-(2-Chloro-5-iodophenyl)-1,2,4-oxadiazol-3-yl]methyl}-2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Product 1

HCID 57800414Methyl 4-chloro-3-(3-{[5-cyano-2-propyl-4-(trifluoromethyl)-1H-indol-1-yl]methyl}-1,2,4-oxadiazol-5-yl)benzoateYield 64%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A solution containing 1-{[5-(2-chloro-5-iodophenyl)-1,2,4-oxadiazol-3-yl]methyl}-2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 291) (0.378 g, 0.662 mmol), 1,1-bisdiphenylphosphinoferrocene (0.073 g, 0.132 mmol), E3N (1.0 mL, 13.6 mmol), Pd(OAc)2 (0.032 g, 0.132 mmol), anhydrous MeOH (2.0 mL) and anhydrous DMF (20 mL). The mixture was then stirred at 70° C. under a carbon monoxide atmosphere for a period of 4 h and then allowed to cooled to rt. The reaction was partitioned between NaHCO3 and EtOAc, dried (MgSO4) and concentrated to dryness. The mixture was purified on a biotage prepak column (0-10% EtOAc-hexanes gradient) to give 0.214 g (64% yield) of pure product: MS (ES) m/z 502 (M+).

Workup

  1. temperatureto cooled to rt
  2. customThe reaction was partitioned between NaHCO3 and EtOAc
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated to dryness
  5. customThe mixture was purified on a biotage prepak column (0-10% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-a5eb9b0baee14edd8a7dcd2355137c69
Source dataset
uspto-grants-2011_09
Patent number
US08026262B2

Reaction notes

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