Reaction Steps
To a mixture of ethyl 2-amino-5-chloronicotinate (143, Example 18) (344.9 mg, 1.719 mmol) in pyridine (2.0 mL, distilled) in a 10 mL round-bottom flask with stirring was added a solution of 3-phenoxyphenylacetyl chloride (812.5 mg, 3.293 mmol) in dry CH2Cl2 (2.0 mL). The mixture was gradually heated to reflux (130° C., oil bath), over which time the CH2Cl2 was allowed to evaporate. The resulting solution was refluxed for 3.5 h, then cooled to room temperature. The reaction mixture was quenched with water (10 mL) and extracted with chloroform (3×15 mL). The combined organic extracts were washed with water (3×10 mL), dried (MgSO4), and rota-evaporated to dryness, leaving a dark green liquid. This liquid was chromatographed on silica gel (24 g, Mallinckrodt, grade 62, mesh 60-200) and eluted with hexanes-EtOAc (1:4, 250 mL). The desired fractions were collected (Rf =0.83) and rota-evaporated to dryness, leaving a green oil. This oil eventually precipitated out as a wet green mass. Crystallization from ethanol afforded the title compound as a light brown flakes, 114 mg (16.1%), mp 103°-4° C.; 1H NMR (CDCl3): δ1.39 (t, J=7.2, 3, CH3CH2), 3.88 (s, 2, benzylic), 4.35 (q, J=7.2, 2, CH3CH2O), 7.10 (m, 9, phenyl), 8.24 (d, J=2.4, 1, py), 8.52 (d, J=2.4, 1, py), 10.70 (d, J=2.4, 1, NH); IR (KBr): 3434, 3155, 2925, 1722, 1659, 1401, 1252, 1205, 1102, 775, 700; HPLC: 99%; LRMS: 410 (M+, 40), 211 (35), 210 (100), 200 (35), 183 (30), 181 (40), 128 (15), 89 (50), 77 (20), 51 (15); HRMS Calcd: 410. 1033. Found: 410.1026.
