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

Participants

Reaction Conditions

Reaction Steps

(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).

Provenance & Evidence