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

HRID 926637Notes

Reaction equation

HRID 926637 reaction equation
[N:1]1([C:6]2[CH:40]=[CH:39][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:30]3[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=3)([C:24]3[N:28]([CH3:29])[CH:27]=[N:26][CH:25]=3)[OH:23])=[CH:16][C:15]=4[CH3:37])=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.[NH:41]1[CH2:44][CH2:43][CH2:42]1>CN(C=O)C>[N:41]1([C:12]2[C:11]([CH2:10][C:9]3[CH:39]=[CH:40][C:6]([N:1]4[CH:5]=[CH:4][CH:3]=[N:2]4)=[CH:7][CH:8]=3)=[C:20]([Cl:21])[C:19]3[C:14](=[C:15]([CH3:37])[CH:16]=[C:17]([C:22]([C:30]4[CH:31]=[CH:32][C:33]([Cl:36])=[CH:34][CH:35]=4)([C:24]4[N:28]([CH3:29])[CH:27]=[N:26][CH:25]=4)[OH:23])[CH:18]=3)[N:13]=2)[CH2:44][CH2:43][CH2:42]1

Participants

4

Reactant 2

HCID 10422AzetidineHCID 74221529(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol2×

Product 1

HCID 118006267{2-Azetidin-1-yl-4-chloro-8-methyl-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-6-yl}(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol (200 mg, 0.34 mmol, Intermediate 67), azetidine (194 mg, 3.40 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 afford the title compound. MS (ESI): mass calcd. for C34H30Cl2N6O, 608.2. m/z found, 609.2 [M+H]+. 1H NMR (600 MHz, CDCl3) δ ppm 7.86 (d, J=2.1 Hz, 1H), 7.84 (d, J=2.4 Hz, 1H), 7.66 (d, J=1.7 Hz, 1H), 7.57-7.54 (m, 2H), 7.37 (dd, J=2.3, 1.1 Hz, 1H), 7.32-7.29 (m, 2H), 7.25 (d, J=8.5 Hz, 2H), 7.19-7.15 (m, 2H), 7.13 (s, 1H), 6.43-6.40 (m, 1H), 6.29 (d, J=1.2 Hz, 1H), 5.80-5.74 (m, 1H), 4.27 (s, 2H), 4.11 (t, J=7.5 Hz, 4H), 3.32 (s, 3H), 2.58 (s, 3H), 2.26-2.17 (m, 2H).

Workup

  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

Sources & evidence

ORD record
ord-63fdfb4d69b049e6a6e3d8ff9ce19606
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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