1,1,1-Trichloropropanone → N-((1R,2R)-1-{[3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-yl)acetamide

Participants

Reaction Steps

To a solution of (1R,2R)-N1-[3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-yl]-2,3-dihydro-1H-indene-1,2-diamine (0.10 g, 0.22 mmol) in CHCl3 (1 mL) at 0°C. under N2 was added trichloroacetone (30 μL, 0.26 mmol). The mixture was allowed to slowly warm to rt for 1.5 hr. The reaction was then heated at 60° C. for 1.5 h. Cool to rt, add additional trichloroacetone (10 μL) and continue heating at 60° C. for 2 hr. The reaction was concentrated and purified by biotage MPLC (90 g column, 80% ethyl acetate/hexanes) to afford 0.11 g (55%) of N-((1R,2R)-1-{[3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-yl)acetamide as a solid: 1H NMR (CDCl3) δ 0.84–1.01, 1.61–1.81, 2.04, 2.80–2.86, 3.58–3.64, 4.07–4.13, 4.46, 5.56, 6.56, 7.28–7.51; MS (ESI+) for C27H26Cl2N4O m/z 493 (M+H)+.

Provenance & Evidence