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 1627286노트

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HRID 1627286 반응식
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]

참가 물질

7

반응물 3

HCID 7859Propargyl alcoholHCID 31268PyrrolidineHCID 66740663HCID 66740663, 화합물

생성물 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)benzoate수율 78%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 8857Ethyl Acetate용매

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온도
80 °C

실험 절차

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+).

후처리

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

출처 및 근거

ORD 기록
ord-2eb7c2c9074e451b97456a3b88577e2b
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785488B2

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