Ammonium Chloride → N-(4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)-N-methyl-3-(trifluoromethyl)-5-(2-(trimethylsilyl)ethylthio)benzamide

HRID 878361ノート

反応式

HRID 878361 の反応式
Br[C:2]1[CH:3]=[C:4]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[C:5]([N:7]([C:9]1[CH:10]=[N:11][C:12]([CH3:24])=[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].[CH3:32][Si:33]([CH3:38])([CH3:37])[CH2:34][CH2:35][SH:36].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]=[C:12]([CH3:24])[N:11]=[CH:10][C:9]=2[N:7]([CH3:8])[C:5](=[O:6])[C:4]2[CH:3]=[C:2]([S:36][CH2:35][CH2:34][Si:33]([CH3:38])([CH3:37])[CH3:32])[CH:27]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:25]=2)=[C:16]([O:22][CH3:23])[CH:17]=1

参加物

9

反応物 5

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 2055212-(Trimethylsilyl)ethanethiolHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 706632723-Bromo-N-[4-(4-fluoro-2-methoxy-phenyl)-6-methyl-pyridin-3-yl]-N-methyl-5-trifluoromethyl-benzamide

生成物 1

HCID 70663427N-(4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)-N-methyl-3-(trifluoromethyl)-5-(2-(trimethylsilyl)ethylthio)benzamide

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

A solution of 3-bromo-N-(4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)-N-methyl-5-(trifluoromethyl)benzamide (0.59 g, 1.19 mmol) and 2-(trimethylsilyl)ethanethiol (159 mg, 187 μL, 1.19 mmol) in dioxane (5.9 mL) was stirred under argon for 5 minutes in a sealed tube. To the clear, light yellow solution were added tris(dibenzylideneacetone)dipalladium (0) (27.2 mg, 29.7 μmol, CAS RN 52409-22-0), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (34.3 mg, 59.3 μmol, CAS RN 161265-03-8) and DIPEA (307 mg, 414 μL, 2.37 mmol) and the reaction mixture was stirred at 120° C. for 5.5 hours, followed by stirring at room temperature overnight. 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 twice by silica gel chromatography on a 20 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 50:50). Off-white solid (0.483 g; 73%). MS (ESI): m/z=551.18 [M+H]+.

後処理

  1. stirringby stirring at room temperature overnight
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted twice with EtOAc
  4. dry with materialThe organic layers were dried over MgSO4
  5. filtrationfiltered
  6. additiontreated with silica gel
  7. customevaporated
  8. customThe compound was purified twice by silica gel chromatography on a 20 g column
  9. washeluting with a gradient of n-heptane:EtOAc (100:0 to 50:50)

出典と根拠

ORDレコード
ord-517d8b5f78564058ba93b904af7e4614
出典データセット
uspto-grants-2015_03
特許番号
US08987307B2

反応ノート

読み込み中…