Dimethylformamide → 1-(4-Chloro-6-{hydroxy(1-methyl-1H-imidazol-5-yl)[6-(trifluoromethyl)pyridin-3-yl]methyl}-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-2-yl)azetidin-3-ol

Participants

Reaction Conditions

Reaction Steps

{2,4-Dichloro-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-6-yl}(1-methyl-1H-imidazol-5-yl)pyrimidin-2-ylmethanol (100 mg, 0.164 mmol, Intermediate 65), 3-hydroxyazetidine hydrochloride (189 mg, 1.64 mmol), and DMF (2 mL) were combined in a reaction tube, then sealed and heated to 100° C. and maintained at that temperature for 24 hours. The reaction solution was taken up into EtOAc, transferred to a reparatory funnel and 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 C33H27ClF3N7O2, 645.2. m/z found, 646.3 [M+H]+. 1H NMR (600 MHz, CD3OD) δ ppm 8.78 (d, J=2.0 Hz, 1H), 8.13 (dd, J=2.5, 0.4 Hz, 1H), 8.06 (d, J=2.0 Hz, 1H), 8.01 (dd, J=8.2, 2.0 Hz, 1H), 7.81 (d, J=8.1 Hz, 1H), 7.76 (d, J=8.8 Hz, 1H), 7.72 (s, 1H), 7.68 (d, J=1.4 Hz, 1H), 7.64-7.59 (m, 2H), 7.57 (dd, J=8.8, 2.2 Hz, 1H), 7.19 (d, J=8.7 Hz, 2H), 6.50-6.46 (m, 1H), 6.35 (s, 1H), 4.55-4.49 (m, 1H), 4.39-4.34 (m, 2H), 4.34 (s, 2H), 3.99-3.93 (m, 2H), 3.48 (s, 3H).

Provenance & Evidence