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 1627299Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1627299
[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]

Komponenten

5

Edukt 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

Produkt 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 methanesulfonateAusbeute 95 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-a5c5540fbdbf4a019fd713533c07ba30
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785488B2

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