Propargyl alcohol → methyl 5-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-2-(3-hydroxyprop-1-ynyl)benzoate

HRID 1627286ノート

反応式

HRID 1627286 の反応式
Br[C:2]1[CH:11]=[CH:10][C:9]([CH2:12][S:13][C:14]2[N:15]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[C:32]([O:37][CH3:38])[CH:31]=3)[C:16]([C:19]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=3)([CH3:21])[CH3:20])=[CH:17][N:18]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH2:39]([OH:42])[C:40]#[CH:41].N1CCCC1>CCOC(C)=O.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:29][C:24]1[CH:23]=[C:22]([C:19]([C:16]2[N:15]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[C:32]([O:37][CH3:38])[CH:31]=3)[C:14]([S:13][CH2:12][C:9]3[CH:10]=[CH:11][C:2]([C:41]#[C:40][CH2:39][OH:42])=[C:3]([CH:8]=3)[C:4]([O:6][CH3:7])=[O:5])=[N:18][CH:17]=2)([CH3:21])[CH3:20])[CH:27]=[CH:26][C:25]=1[Cl:28]

参加物

7

反応物 3

HCID 7859Propargyl alcoholHCID 31268PyrrolidineHCID 66740663HCID 66740663、化合物

生成物 1

HCID 66740390methyl 5-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-2-(3-hydroxyprop-1-ynyl)benzoate収率 78%

試薬・触媒・溶媒 3

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HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

To a stirred solution of methyl 2-bromo-5-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)benzoate (506 mg, 0.79 mmol, 1.0 eq), propargyl alcohol (0.07 mL, 1.2 mmol, 1.5 eq) and pyrrolidine (0.1 mL, 1.2 mmol, 1.5 eq) in dry, degassed DMF (4 mL) was added PdCl2(dppf)2 (30 mg, 0.04 mmol, 5 mol %) and CuI (15 mg, 0.08 mmol, 10 mol %). The reaction mixture was heated at 80° C. for 5 h at which time LCMS showed 85% conversion. The mixture was diluted with EtOAc, washed with brine, dried and concentrated. Purification by column chromatography (0 to 75% EtOAc/Hexanes) provided 378 mg (78% yield) of methyl 5-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-2-(3-hydroxyprop-1-ynyl)benzoate. MS (EI) m/z 615 (MH+).

後処理

  1. customdegassed DMF (4 mL)
  2. washwashed with brine
  3. customdried
  4. concentrationconcentrated
  5. customPurification by column chromatography (0 to 75% EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-2eb7c2c9074e451b97456a3b88577e2b
出典データセット
uspto-grants-2014_07
特許番号
US08785488B2

反応ノート

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