Ammonium Chloride → N-[4-(4-Fluoro-2-methoxy-phenyl)-6-methyl-pyridin-3-yl]-N-methyl-3-(oxetan-3-ylsulfanyl)-5-trifluoromethyl-benzamide

HRID 878359Notes

Reaction equation

HRID 878359 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10][C:9]=2[N:15]([CH3:29])[C:16](=[O:28])[C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([SH:27])[CH:18]=2)=[C:4]([O:30][CH3:31])[CH:3]=1.I[CH:33]1[CH2:36][O:35][CH2:34]1.CCN(C(C)C)C(C)C.[NH4+].[Cl-]>C(#N)C.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10][C:9]=2[N:15]([CH3:29])[C:16](=[O:28])[C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([S:27][CH:33]3[CH2:36][O:35][CH2:34]3)[CH:18]=2)=[C:4]([O:30][CH3:31])[CH:3]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 133566863-IodooxetaneHCID 70663671N-(4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)-3-mercapto-N-methyl-5-(trifluoromethyl)benzamide

Product 1

HCID 70663579N-[4-(4-Fluoro-2-methoxy-phenyl)-6-methyl-pyridin-3-yl]-N-methyl-3-(oxetan-3-ylsulfanyl)-5-trifluoromethyl-benzamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)-3-mercapto-N-methyl-5-(trifluoromethyl)benzamide (0.093 g, 206 μmol) in acetonitrile (2 mL) were added 3-iodooxetane (57.0 mg, 310 μmol) and DIPEA (66.7 mg, 90.1 μL, 516 μmol) and the clear, light yellow solution was heated under reflux for 2.5 hours. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 10 g column using an MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Colorless foam (0.05 g; 47%). MS (ESI): m/z=507.14 [M+H]+.

Workup

  1. temperaturethe clear, light yellow solution was heated
  2. temperatureunder reflux for 2.5 hours
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted twice with EtOAc
  5. dry with materialThe organic layers were dried over MgSO4
  6. filtrationfiltered
  7. additiontreated with silica gel
  8. customevaporated
  9. customThe compound was purified by silica gel chromatography on a 10 g column
  10. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)

Sources & evidence

ORD record
ord-44a02e63df7141dcae273ee7f538b1b3
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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