Dimethylacetamide → 6-((3,5-Dimethylisoxazol-4-yl)(hydroxy)(1-methyl-1H-1,2,3-triazol-5-yl)methyl)-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline-4-carbonitrile

Participants

Reaction Conditions

Reaction Steps

(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(3,5-dimethylisoxazol-4-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol (180 mg, 0.32 mmol, Example 93), zinc cyanide (77 mg, 0.66 mol), X-phos (45 mg, 0.94 mmol), Pd2(dba)3 (50 mg, 0.055 mmol) and zinc metal (3 mg, 0.19 mmol) were added to a large microwave vial. DMA (4 mL, sparged with argon for 35 minutes) was added and the vial was sealed and evacuated. The mixture was heated to 125° C. in a preheated aluminum heating mantle. After 1 hour, the mixture was allowed to cool to room temperature and then was filtered through a Celite® pad and rinsed with EtOAc-MeOH (10:1). The effluent was concentrated under reduced pressure and the crude material was chromatographed directly on silica gel (20% EtOAc-hexanes increasing to 50% EtOAc) to provide the title compound as an off white solid. 1H NMR (500 MHz, CDCl3) δ 8.17 (d, J=2.1 Hz, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.53 (d, J=8.2 Hz, 2H), 7.46 (d, J=8.2 Hz, 2H), 7.40 (dd, J=8.8, 2.2 Hz, 1H), 6.92 (s, 1H), 5.38 (s, 1H), 4.43-4.29 (m, 2H), 4.12 (s, 3H), 4.01 (s, 3H), 1.95 (s, 3H), 1.82 (s, 3H); MS (ESI): mass calc. for Chemical Formula: C28H23F3N6O3; Exact Mass: 548.2. m/z found 549.0 (M+H).

Provenance & Evidence