Methanesulfonyl chloride → 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 1627299노트

반응식

HRID 1627299 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].CCN(C(C)C)C(C)C.[CH3:48][S:49](Cl)(=[O:51])=[O:50]>C(Cl)Cl>[CH3:48][S:49]([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:51])=[O:50]

참가 물질

5

반응물 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 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 95%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a stirred solution of 2-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethanol (3.8 g, 6.75 mmol) and DIPEA (3.52 mL, 20.3 mmol) in DCM (100 mL) at 0° C. was added methanesulfonyl chloride (603 μL, 7.8 mmol). After the reaction was slowly warmed to ambient temperature over 30 min, it was partitioned in DCM (100 mL) and water (100 mL). Organic layer was dried over MgSO4 and evaporated in vacuo. The residue was purified by column chromatography (Hex/EtOAc=1:3) to give 2-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethyl methanesulfonate (4.1 g, 95% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.16 (d, J=8.25 Hz, 1H), 7.22 (s, 1H), 6.82-6.72 (m, 2H), 6.58-6.47 (m, 2H), 6.42-6.32 (m, 4H), 4.55 (dd, J=5.27, 3.62 Hz, 2H), 4.18 (dd, J=5.26, 3.64 Hz, 2H), 4.04 (s, 2H), 3.78 (s, 3H), 3.09 (s, 3H), 1.50 (d, J=10.49 Hz, 6H).

후처리

  1. customit was partitioned in DCM (100 mL)
  2. dry with materialOrganic layer was dried over MgSO4
  3. customevaporated in vacuo
  4. customThe residue was purified by column chromatography (Hex/EtOAc=1:3)

출처 및 근거

ORD 기록
ord-a5c5540fbdbf4a019fd713533c07ba30
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785488B2

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