Azetidine → {2-Azetidin-1-yl-4-chloro-8-methyl-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-6-yl}(1-methyl-1H-imidazol-5-yl)[6-(trifluoromethyl)pyridin-3-yl]methanol

HRID 926638Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 926638
[N:1]1([C:6]2[CH:43]=[CH:42][C:9]([CH2:10][C:11]3[C:12](Cl)=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17]([C:22]([C:34]3[N:38]([CH3:39])[CH:37]=[N:36][CH:35]=3)([C:24]3[CH:25]=[N:26][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:28][CH:29]=3)[OH:23])=[CH:16][C:15]=4[CH3:40])=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.[NH:44]1[CH2:47][CH2:46][CH2:45]1>CN(C=O)C>[N:44]1([C:12]2[C:11]([CH2:10][C:9]3[CH:8]=[CH:7][C:6]([N:1]4[CH:5]=[CH:4][CH:3]=[N:2]4)=[CH:43][CH:42]=3)=[C:20]([Cl:21])[C:19]3[C:14](=[C:15]([CH3:40])[CH:16]=[C:17]([C:22]([C:34]4[N:38]([CH3:39])[CH:37]=[N:36][CH:35]=4)([C:24]4[CH:25]=[N:26][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:28][CH:29]=4)[OH:23])[CH:18]=3)[N:13]=2)[CH2:47][CH2:46][CH2:45]1

Komponenten

4

Edukt 2

HCID 10422AzetidineHCID 86715672(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol2×

Produkt 1

HCID 118006794{2-Azetidin-1-yl-4-chloro-8-methyl-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-6-yl}(1-methyl-1H-imidazol-5-yl)[6-(trifluoromethyl)pyridin-3-yl]methanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol (200 mg, 0.321 mmol, Intermediate 68), azetidine (183 mg, 3.21 mmol), and DMF (2 mL) were combined in a reaction tube, then sealed and heated to 100° C. and maintained at that temperature overnight. The reaction vessel was then cooled to room temperature and the solvent and excess azetidine were removed by reduced pressure distillation. The crude residue was taken up into EtOAc, then extracted twice with a saturated, aqueous NH4Cl solution. The organic phase was separated, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified via reverse phase chromatography using acetonitrile with ammonium hydroxide in water as eluent to provide the title compound. MS (ESI): mass calcd. for C34H29ClF3N7O, 643.2. m/z found, 644.3 [M+H]+. 1H NMR (600 MHz, CDCl3) δ ppm 8.82 (d, J=2.2 Hz, 1H), 7.90-7.86 (m, 2H), 7.85 (d, J=2.5 Hz, 1H), 7.66 (d, J=1.7 Hz, 1H), 7.61-7.58 (m, 1H), 7.58-7.54 (m, 2H), 7.36 (dd, J=2.3, 1.1 Hz, 1H), 7.19-7.15 (m, 2H), 7.14 (d, J=1.1 Hz, 1H), 6.73 (s, 1H), 6.45-6.40 (m, 1H), 6.24 (d, J=1.1 Hz, 1H), 4.29 (s, 2H), 4.13 (t, J=7.5 Hz, 4H), 3.33 (s, 3H), 2.58 (s, 3H), 2.28-2.19 (m, 2H).

Aufarbeitung

  1. customsealed
  2. temperaturemaintained at that temperature overnight
  3. temperatureThe reaction vessel was then cooled to room temperature
  4. customthe solvent and excess azetidine were removed by reduced pressure distillation
  5. extractionextracted twice with a saturated, aqueous NH4Cl solution
  6. customThe organic phase was separated
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude material was purified via reverse phase chromatography

Quellen und Nachweise

ORD-Eintrag
ord-6b22b21ffa1e4c8ba8dc9ff598c6a030
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09284308B2

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