Methyl iodide → N-[3-Bromo-4-(1,2,3,6-tetrahydropyrid-4-ylmethylthio)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxamide

HRID 617739Notes

Reaction equation

HRID 617739 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][C:28]([C:31]4[N:35]=[C:34]([CH3:36])[O:33][N:32]=4)=[CH:27][C:26]=3[CH3:37])=[CH:21][CH:20]=2)=[O:18])[CH:5]=[CH:6][C:7]=1[S:8][CH2:9][C:10]1[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=1.CI.[BH4-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]([C:19]2[CH:20]=[CH:21][C:22]([C:25]3[CH:30]=[CH:29][C:28]([C:31]4[N:35]=[C:34]([CH3:36])[O:33][N:32]=4)=[CH:27][C:26]=3[CH3:37])=[CH:23][CH:24]=2)=[O:18])[CH:5]=[CH:6][C:7]=1[S:8][CH2:9][C:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH:11]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 4311764Sodium borohydrideHCID 21849677N-[3-bromo-4-(pyrid-4-ylmethylthio)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxamide

Product 1

HCID 21849678N-[3-Bromo-4-(1,2,3,6-tetrahydropyrid-4-ylmethylthio)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxamideYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A stirred solution of N-[3-bromo-4-(pyrid-4-ylmethylthio)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxamide (D 16) (1.41 g, 2.46 mmol) in dry DMF (15 ml) was treated with methyl iodide (0.184 ml, 2.95 mmol). After 60 h, the reaction mixture was evaporated under reduced pressure and the residue was triturated with ethyl acetate. The resultant brown solid was filtered off and dried in vacuo. It was redissolved in a mixture of ethanol (150 ml) and water (75 ml), cooled to 0° C. and treated with sodium borohydride (0.165 g, 4.35 mmol) slowly with stirring. After 1 h, the reaction mixture was treated with potassium carbonate solution (50 ml). The resultant suspension was extracted with dichloromethane (3×100 ml) and the combined organic layers were dried (Na2SO4) and evaporated under reduced pressure to give a brown solid, which was purified by silica gel chromatography (10% MeOH/CH2Cl2 as eluant) to give the title compound as a yellow oil (0.680 g, 47%).

Workup

  1. customthe reaction mixture was evaporated under reduced pressure
  2. customthe residue was triturated with ethyl acetate
  3. filtrationThe resultant brown solid was filtered off
  4. customdried in vacuo
  5. dissolutionIt was redissolved in a mixture of ethanol (150 ml) and water (75 ml)
  6. waitAfter 1 h
  7. extractionThe resultant suspension was extracted with dichloromethane (3×100 ml)
  8. dry with materialthe combined organic layers were dried (Na2SO4)
  9. customevaporated under reduced pressure
  10. customto give a brown solid, which
  11. customwas purified by silica gel chromatography (10% MeOH/CH2Cl2 as eluant)

Sources & evidence

ORD record
ord-ee1ca2b27d714c7381880e7494a6c5ec
Source dataset
uspto-grants-1999_09
Patent number
US05952325

Reaction notes

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