Toluene → N-(4-chlorophenyl)-N-methyl-2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-4-amine

Participants

Reaction Conditions

Reaction Steps

The mixture of 3-[4-bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]-2-methylpyrazolo[1,5-a]pyridine (0.0700 g, 0.142 mmol), p-Chloro-N-methylaniline (33.5 mg, 0.236 mmol), Tris(dibenzylideneacetone)dipalladium(0) (4.4 mg, 0.0048 mmol.), racemic 1,1′-binaphthalene-2,2′-diylbis(diphenylphosphine) (8.8 mg, 0.014 mmol) and Sodium tert-butoxide (22.7 mg, 0.236 mmol) in dry Toluene (2.0 mL, 19 mmol) was degassed by vacuum and backfilling with N2 for 5 times, sonicated under N2 for 1 min to dissolve all material, degassed for 5 more times. The resulted brown solution was heated under N2 in a capped vial to 112° C. for 18 hours. The mixture was partitioned in EtOAc (80 mL) and water (30 mL). The EtOAc layer was washed with water, brine, dried over Na2SO4, filtered, rotavaped to give a crude product. Chromatograph in a 24 g ISCO column using EtOAc/hexane (0/100 to 40/60) afforded a solid product (0.059 g, 75% yield). LCMS: (FA) ES+ 552, 554. 1H NMR (400 MHz, d1-chloroform) δ 8.43 (d, J=6.53 Hz, 1H), 8.32 (d, J=9.04 Hz, 1H), 8.13 (s, 1H), 7.29-7.33 (m, 1H), 7.10-7.12 (d, J=9.04 Hz, 2H), 6.84-6.88 (m, 1H), 6.82-6.84 (d, J=9.04 Hz, 2H), 5.39 (s, 2H), 3.55 (t, J=7.78 Hz, 2H), 3.51 (s, 3H), 2.78 (s, 3H), 0.90 (t, J=7.78 Hz, 2H), 0.00 (s, 9H).

Provenance & Evidence