Water → 3-{4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-[4-(methylsulfonyl)-1-piperazinyl]-1,3,5-triazin-2-yl}-8-oxa-3-azabicyclo[3.2.1]octane

HRID 1619818Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1619818
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[F:6][CH:7]([F:39])[C:8]1[N:12]([C:13]2[N:18]=[C:17]([N:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[N:16]=[C:15]([N:25]3[CH2:31][CH:30]4[O:32][CH:27]([CH2:28][CH2:29]4)[CH2:26]3)[N:14]=2)[C:11]2[CH:33]=[CH:34][CH:35]=[C:36]([O:37][CH3:38])[C:10]=2[N:9]=1.C([O-])([O-])=O.[K+].[K+].O>C(Cl)Cl>[F:39][CH:7]([F:6])[C:8]1[N:12]([C:13]2[N:18]=[C:17]([N:19]3[CH2:24][CH2:23][N:22]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:21][CH2:20]3)[N:16]=[C:15]([N:25]3[CH2:31][CH:30]4[O:32][CH:27]([CH2:28][CH2:29]4)[CH2:26]3)[N:14]=2)[C:11]2[CH:33]=[CH:34][CH:35]=[C:36]([O:37][CH3:38])[C:10]=2[N:9]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 666980973-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(1-piperazinyl)-1,3,5-triazin-2-yl]-8-oxa-3-azabicyclo[3.2.1]octane

Produkt 1

HCID 469178653-{4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-[4-(methylsulfonyl)-1-piperazinyl]-1,3,5-triazin-2-yl}-8-oxa-3-azabicyclo[3.2.1]octaneAusbeute 89 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Methanesulfonyl chloride (0.12 mL, 1.55 mmol) was added dropwise to a stirred suspension of 3-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(1-piperazinyl)-1,3,5-triazin-2-yl]-8-oxa-3-azabicyclo[3.2.1]octane (165 mg, 0.349 mmol) and powdered K2CO3 (434 mg, 3.15 mmol) in CH2Cl2 (5 mL) at 0° C. The reaction mixture was allowed to warm to room temperature and was stirred for 3 days. Water was added, the phases were separated and the aqueous phase was extracted with CH2Cl2. The combined organic phases were dried (Na2SO4) and the solvent removed under vacuum. Chromatography on silica, eluting with CH2Cl2/MeOH (99:1), followed by recrystallization from CH2Cl2/MeOH gave 170 mg (89% yield) of 3-{4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-[4-(methylsulfonyl)-1-piperazinyl]-1,3,5-triazin-2-yl}-8-oxa-3-azabicyclo[3.2.1]octane: mp (CH2Cl2/MeOH) 312-314° C.; 1H NMR (CDCl3) δ7.86 (dd, J=8.4, 0.6 Hz, 1H), 7.45 (t, JHF=53.6 Hz, 1H), 7.36 (t, J=8.2 Hz, 1H), 6.82 (d, J=7.8 Hz, 1H), 4.49 (br s, 2H), 4.32 (d, J=13.2 Hz, 2H), 4.05 (s, 3H), 4.02 (br s, 4H), 3.30 (m, 6H), 2.81 (s, 3H), 1.99 (m, 2H), 1.79 (m, 2H); Anal. Calcd. for C23H28F2N8O4S: C, 50.2; H, 5.1; N, 20.35. Found: C, 50.3; H, 5.1; N, 20.5.

Aufarbeitung

  1. customthe phases were separated
  2. extractionthe aqueous phase was extracted with CH2Cl2
  3. dry with materialThe combined organic phases were dried (Na2SO4)
  4. customthe solvent removed under vacuum
  5. washChromatography on silica, eluting with CH2Cl2/MeOH (99:1)
  6. customfollowed by recrystallization from CH2Cl2/MeOH

Quellen und Nachweise

ORD-Eintrag
ord-3c8fc3424add4be49721c561be3daebf
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772287B2

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