Dimethylacetamide → HCID 86715671, compound

Participants

Reaction Conditions

Reaction Steps

(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol (250 mg, 0.44 mmol, Example 77A), zinc cyanide (90 mg, 0.77 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (X-phos, 40 mg, 0.084 mmol), zinc powder (8 mg, 0.12 mmol), tris(dibenzylideneacetone)dipalladium(0), (Pd2(dba)3; 60 mg, 0.066 mmol) were added to a large microwave vial, then dimethylacetamide (7 mL, degassed with argon) was added and the vial was sealed and evacuated. The mixture was heated to 125° C. in an aluminum heating mantle. The mixture was cooled to 80° C. and then filtered through a Celite® pad and rinsed with EtOAc-MeOH (10:1, v/v) and the light brown filtrate was concentrated under vacuum to afford a brown oil. The crude material was chromatographed directly on silica gel (100% DCM increasing to 10% MeOH-DCM) which provided the product contaminated with dimethylacetamide. This material was further purified by RP-HPLC to the title compound as a white foam. MS m/e 559.2 [M+H]+. 1H NMR (500 MHz, CDCl3) δ ppm 8.05 (s, 1H), 7.92 (d, J=8.8 Hz, 1H), 7.59 (d, J=8.3 Hz, 1H), 7.53 (d, J=8.2 Hz, 2H), 7.45 (d, J=8.2 Hz, 2H), 7.42-7.34 (m, 2H), 7.06 (s, 1H), 4.37 (s, 2H), 4.13 (s, 3H), 3.94 (s, 3H), 2.77 (s, 3H), 2.62 (s, 3H). The racemic material was separated into its individual enantiomers using the following conditions: Chiralpack OD, 80% heptanes:20% ethanol; wavelength at 220 nM to provide the two enantiomers. The first eluting enantiomer was Example 78B and the second eluting enantiomer was Example 78C.

Provenance & Evidence