Dimethylacetamide → HCID 73442863, compound

Participants

Reaction Conditions

Reaction Steps

(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol (370 mg, 0.66 mmol, Example 80A), zinc cyanide (147 mg, 1.26 mmol), X-phos (64.5 mg, 0.14 mmol), zinc powder (12 mg, 0.19 mmol) tris(dibenzylideneacetone)dipalladium (0), (Pd2(dba)3, 98 mg, 0.11 mmol) were added to a large microwave vial, then DMA (8 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 (for how long?). The mixture was filtered through a Celite® pad while still warm, rinsed with EtOAc-MeOH (10:1) and concentrated under vacuum providing a brown oil. The crude material was purified by RP-HPLC to give the title compound as an off white solid. MS m/e 548.2 [M+H]+. 1H NMR (500 MHz, CDCl3) δ ppm 8.19 (s, 1H), 7.87 (d, J=8.7 Hz, 1H), 7.50 (d, J=8.3 Hz, 2H), 7.42 (apparent d, 8.1 Hz, 3H), 7.3-7.4 (m, 1H) 6.41 (s, 1H), 4.41-4.26 (m, 2H), 4.10 (s, 3H), 3.90 (s, 3H), 3.64 (s, 3H), 2.58 (s, 3H). The racemic material was separated into its individual enantiomers using the following conditions: Chiralpak IA SFC column (5 u), 85% hexane: 15% EtOH (containing 0.2% Et3N) to provide the two enantiomers. The first eluting enantiomer was Example 81B and the second eluting enantiomer was Example 81C.

Provenance & Evidence