Ammonium Chloride → N-(4-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)-N-methyl-3-(trifluoromethyl)-5-(2-(trimethylsilyl)ethylthio)benzamide

HRID 878248Notes

Reaction equation

HRID 878248 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1)[C:5]([N:7]([C:9]1[CH:10]=[N:11][CH:12]=[CH:13][C:14]=1[C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=1[O:22][CH3:23])[CH3:8])=[O:6].[CH3:31][Si:32]([CH3:37])([CH3:36])[CH2:33][CH2:34][SH:35].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.CCN(C(C)C)C(C)C.[NH4+].[Cl-]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O>[F:21][C:18]1[CH:19]=[CH:20][C:15]([C:14]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:7]([CH3:8])[C:5](=[O:6])[C:4]2[CH:3]=[C:2]([S:35][CH2:34][CH2:33][Si:32]([CH3:37])([CH3:36])[CH3:31])[CH:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:24]=2)=[C:16]([O:22][CH3:23])[CH:17]=1

Participants

9

Reactant 5

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 2055212-(Trimethylsilyl)ethanethiolHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 706633173-bromo-N-(4-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)-N-methyl-5-(trifluoromethyl)benzamide

Product 1

HCID 70663298N-(4-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)-N-methyl-3-(trifluoromethyl)-5-(2-(trimethylsilyl)ethylthio)benzamide

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 3-bromo-N-(4-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)-N-methyl-5-(trifluoromethyl)benzamide (0.135 g, 279 μmol) and 2-(trimethylsilyl)ethanethiol (37.5 mg, 44.1 μL, 279 μmol) in dioxane (2 mL) was stirred under argon for 5 minutes in a sealed tube. To the clear light yellow solution were added tris(dibenzylideneacetone)dipalladium(0) (6.4 mg, 6.98 μmol, CAS RN 52409-22-0) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (8.08 mg, 14.0 μmol, CAS RN 161265-03-8) and DIPEA (72.2 mg, 97.6 μL, 559 μmol) and the reaction mixture was stirred at 120° C. After stirring for 4 hours in a sealed tube, heating was stopped. 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 20 g column using an MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Colorless solid (0.116 g; 77%). MS (ESI): m/z=537.17 [M+H]+.

Workup

  1. stirringAfter stirring for 4 hours in a sealed tube
  2. temperatureheating
  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 20 g column
  10. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)

Sources & evidence

ORD record
ord-0c6d852a7b894be5a9ee42f04f77dd95
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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