Diisopropylamine → 2-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethyl methanesulfonate

HRID 83844노트

반응식

HRID 83844 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([S:23][CH2:24][C:25]3[C:34]([F:35])=[CH:33][C:28]([O:29][CH2:30][CH2:31][OH:32])=[CH:27][C:26]=3[F:36])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:37][CH3:38].[CH3:39][S:40](Cl)(=[O:42])=[O:41].C(NC(C)C)(C)C>C(Cl)Cl>[CH3:39][S:40]([O:32][CH2:31][CH2:30][O:29][C:28]1[CH:27]=[C:26]([F:36])[C:25]([CH2:24][S:23][C:14]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:11]([C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([O:37][CH3:38])[CH:4]=3)([CH3:10])[CH3:9])=[CH:12][N:13]=2)=[C:34]([F:35])[CH:33]=1)(=[O:42])=[O:41]

참가 물질

5

반응물 3

HCID 7912DiisopropylamineHCID 31297Methanesulfonyl chlorideHCID 667407372-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethanol

생성물 1

HCID 866622302-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethyl methanesulfonate수율 75%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To 2-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethanol (270 mg, 0.48 mmol, 1.0 eq) in DCM (2.5 mL) was added methanesulfonyl chloride (0.1 mL, 1.44 mmol, 3.0 eq), followed by diisopropylamine (0.25 mL, 1.44 mmol, 3.0 eq). The reaction mixture was stirred at room temperature for 45 min at which time LCMS showed complete consumption of starting material. Aqueous work up (EtOAc and water) followed by purification (column chromatography, 0 to 80% EtOAc/Hex) provided 2-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethyl methanesulfonate (230 mg, 75%) as a white foam. MS (EI) m/z 462 (MH+).

후처리

  1. customconsumption of starting material
  2. customAqueous work up (EtOAc and water) followed by purification (column chromatography, 0 to 80% EtOAc/Hex)

출처 및 근거

ORD 기록
ord-d39a76728847463d8b281645e2711671
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846739B2

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