Methyl iodide → Ethyl 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1-methyl-1H-indol-3-yl]propanoate

HRID 1512828Notes

Reaction equation

HRID 1512828 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[CH:20][C:21]([F:34])=[C:22]4[C:26]=3[NH:25][CH:24]=[C:23]4[CH2:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].I[CH3:36].[OH-].[K+]>CS(C)=O>[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[CH:20][C:21]([F:34])=[C:22]4[C:26]=3[N:25]([CH3:36])[CH:24]=[C:23]4[CH2:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:11])[CH3:12])#[N:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 14797Potassium HydroxideHCID 59146114ethyl 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1H-indol-3-yl]propanoate

Product 1

HCID 59146068Ethyl 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1-methyl-1H-indol-3-yl]propanoate

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of ethyl 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1H-indol-3-yl]propanoate (D47) (450 mg) and iodomethane (0.91 mL) in dimethyl sulfoxide (DMSO) (15 mL) at room temperature was added potassium hydroxide (218 mg). The reaction mixture was stirred at room temperature for 5 h. The reaction mixture was quenched with saturated ammonium chloride, extracted with EtOAc for 3 times. The organic phase was washed with brine, dried over anhydrous sodium sulphate and evaporated in vacuo to afford the crude product. Purification by column chromatography affords ethyl 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1-methyl-1H-indol-3-yl]propanoate (D130) (349 mg). MS (ES): C26H25FN4O4 requires 476; found 477.3 (M+H+)

Workup

  1. customThe reaction mixture was quenched with saturated ammonium chloride
  2. extractionextracted with EtOAc for 3 times
  3. washThe organic phase was washed with brine
  4. dry with materialdried over anhydrous sodium sulphate
  5. customevaporated in vacuo
  6. customto afford the crude product
  7. customPurification by column chromatography

Sources & evidence

ORD record
ord-7dec911553fa4a499de10fa327cfe555
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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