Pyrrolidine → 3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)-N,N-dimethylprop-2-yn-1-amine

HRID 83840

反応式

HRID 83840 の反応式
Br[C:2]1[CH:33]=[C:32]([F:34])[C:5]([CH2:6][S:7][C:8]2[N:9]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:10]([C:13]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([O:23][CH3:24])[CH:17]=3)([CH3:15])[CH3:14])=[CH:11][N:12]=2)=[C:4]([F:35])[CH:3]=1.[CH3:36][N:37]([CH3:41])[CH2:38][C:39]#[CH:40].N1CCCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Cu]I>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([C:13]([C:10]2[N:9]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:8]([S:7][CH2:6][C:5]3[C:32]([F:34])=[CH:33][C:2]([C:40]#[C:39][CH2:38][N:37]([CH3:41])[CH3:36])=[CH:3][C:4]=3[F:35])=[N:12][CH:11]=2)([CH3:15])[CH3:14])=[CH:17][C:18]=1[O:23][CH3:24]

参加物

6

反応物 3

HCID 31268PyrrolidineHCID 81643N,N-DimethylpropargylamineHCID 667405782-(4-bromo-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole

生成物 1

HCID 672365113-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)-N,N-dimethylprop-2-yn-1-amine収率 95%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒

反応条件

温度
80 °C

実験手順

To a solution of 2-(4-bromo-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole (250 mg, 0.43 mmol, 1.0 eq), N,N-dimethylprop-2-yn-1-amine (0.07 mL, 0.64 mmol, 1.5 eq) and pyrrolidine (0.05 mL, 0.64 mmol, 1.5 eq) in dry, degassed DMF (2 mL) were added PdCl2(dppf)2 (16 mg, 0.022 mmol, 5 mol %) and CuI (8 mg, 0.043 mmol, 10 mol %). The reaction mixture was heated at 80° C. for 16 h, at which time LCMS showed complete consumption of starting material. The mixture was diluted with EtOAc, washed with brine, dried and concentrated. Purification by column chromatography (0 to 15% MeOH/DCM) furnished 238 mg (95% yield) of 3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)-N,N-dimethylprop-2-yn-1-amine as a brown oil: MS (EI): 584 (MH+).

後処理

  1. customdegassed DMF (2 mL)
  2. customconsumption of starting material
  3. additionThe mixture was diluted with EtOAc
  4. washwashed with brine
  5. customdried
  6. concentrationconcentrated
  7. customPurification by column chromatography (0 to 15% MeOH/DCM)

出典と根拠

ORDレコード
ord-23485bfa6a9a4682ae91505b2978e3ce
出典データセット
uspto-grants-2014_09
特許番号
US08846739B2

関連ノート

読み込み中…