1,3-Dibromopropane → (R)-methyl 2-(N-(3-bromopropyl)-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)propanoate

HRID 83847Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 83847
[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:30]([F:31])=[CH:29][C:28]([S:32]([NH:35][C@H:36]([CH3:41])[C:37]([O:39][CH3:40])=[O:38])(=[O:34])=[O:33])=[CH:27][C:26]=3[F:42])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:43][CH3:44].C([O-])([O-])=O.[K+].[K+].[Br:51][CH2:52][CH2:53][CH2:54]Br>CC#N>[Br:51][CH2:52][CH2:53][CH2:54][N:35]([C@H:36]([CH3:41])[C:37]([O:39][CH3:40])=[O:38])[S:32]([C:28]1[CH:27]=[C:26]([F:42])[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:43][CH3:44])[CH:4]=3)([CH3:9])[CH3:10])=[CH:12][N:13]=2)=[C:30]([F:31])[CH:29]=1)(=[O:33])=[O:34]

Komponenten

5

Edukt 3

HCID 80011,3-DibromopropaneHCID 11430Potassium CarbonateHCID 68070481(R)-Methyl 2-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)propanoate

Produkt 1

HCID 67237163(R)-methyl 2-(N-(3-bromopropyl)-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)propanoateAusbeute 47 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of (R)-methyl 2-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)propanoate (200 mg, 0.30 mol) in MeCN (4 mL) were added K2CO3 (124 mg, 0.90 mol) and 1,3-dibromopropane (121 mg, 0.60 mol). The reaction flask was heated at 60° C. for 4 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting product was purified by column chromatography (silica, Hex/EtOAc, 1:1) to afford (R)-methyl 2-(N-(3-bromopropyl)-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)propanoate (113 mg, 47%) as a white foam. 1H NMR (400 MHz, CDCl3) δ 7.28 (d, 2H), 7.19 (s, 1H), 7.16-7.18 (d, 1H), 6.80-6.84 (t, 2H), 6.50-6.53 (m, 2H), 6.43-6.46 (m, 2H), 4.63-4.65 (q, 1H), 4.13 (s, 2H), 3.72 (s, 3H), 3.55 (s, 3H), 3.27-3.45 (m, 4H), 2.10-2.31 (m, 2H), 1.47 (s, 6H), 1.45 (s, 3H).

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. customThe resulting product was purified by column chromatography (silica, Hex/EtOAc, 1:1)

Quellen und Nachweise

ORD-Eintrag
ord-2566fb4933a543eeb593f6a8e5dd3050
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846739B2

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