Cesium carbonate → 5-(2,4-dichlorophenyl)-N-[(3R,4S)-4-ethoxy-1-(1,3-thiazol-2-yl)pyrrolidin-3-yl]-3,6-diethylpyrazin-2-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-(2,4-dichlorophenyl)-N-[(3R,4S)-4-ethoxypyrrolidin-3-yl]-3,6-diethylpyrazin-2-amine (120 mg) in ethylene glycol dimethyl ether (0.586 ml) was added 2-bromo-1,3-thiazole (0.040 ml, 1.5 eq.), Cesium carbonate (144 mg, 1.5 eq.), N-[2′-(dicyclohexylphosphino)-1,1′-biphenyl-2-yl]-N,N-dimethylamine (16 mg, 0.14 eq.) and Tris(dibenzylideneacetone)dipalladium (19 mg, 0.7 eq.). The reaction mixture was heated at 100° C. for 16 h, poured into saturated sodium bicarbonate (50 ml), extracted 2×50 ml of CH2Cl2, dried MgSO4, filtered and concentrated. Purification via MPLC chromatography eluting with 10–30% ethyl acetate/heptane provided the title compound as an amorphous solid (77 mg, 50%): 1H NMR (400 MHz, CDCl3) δ) 7.50, 7.34, 7.28–7.23, 6.53, 5.30, 4.92, 4.27, 4.02, 3.82–3.72, 3.55, 3.46, 2.72, 2.48, 1.33–1.27, 1.16; IR (liq.) 2972 (s), 2934, 2335 (w), 1564 (s), 1539 (s), 1494 (s), 1470 (s), 1396 (s), 1357, 1350, 1201, 1141, 1121 (s), 1101, 610 cm−1 HRMS (ESI) calcd for C23H27N5OSCl2+H1 492.1391. found 492.1378.

Provenance & Evidence