57% |
With N-ethyl-N,N-diisopropylamine In acetonitrile at 100℃; for 24h; Inert atmosphere; |
1-Morpholino-2-((4-propylpyrimidin-2-yl)amino)ethanone (1s)
A solution of 2-chloro-4-propylpyrimidine (235 mg, 1.50 mmol), 2-amino-1-morpholinoethanone hydrochloride (298 mg, 1.65 mmol) and DIPEA (0.655 mL, 3.75 mmol) in acetonitrile (2.5 mL) was stirred at 100 °C for 24 hr. The reaction mixture was partitioned between ethyl acetate (10 mL) and water (10 mL), and the organic layer was washed with water (10 mL). The aqueous was back-extracted with ethyl acetate (5 x 10 mL) and the combined organic layers were dried through a hydrophobic frit and evaporated to dryness. The crude product was purified by silica chromatography (0-70 % (3:1 ethylacetate:ethanol + 1 % triethylamine)/cyclohexane). Appropriate fractions were evaporated to dryness toafford 1-morpholino-2-((4-propylpyrimidin-2-yl)amino)ethanone (224 mg, 0.847 mmol, 57% yield) as acolourless gum. LCMS (High pH, ES+): tR = 0.75 min, [M+H]+ 265.2. 1H NMR (400 MHz, CDCl3) δ 0.96 (t, J = 7.5 Hz, 3 H), 1.71 (tq, J = 7.6, 7.5 Hz, 2 H), 2.54 (t, J = 7.6 Hz, 2 H), 3.46 - 3.56 (m, 2 H), 3.63 - 3.75 (m, 6 H), 4.20 (d, J = 4.3 Hz, 2 H), 6.03 (br. s., 1 H), 6.44 (d, J = 5.1 Hz, 1 H), 8.16 (d, J = 5.1 Hz, 1 H). 13C NMR (101 MHz, CDCl3) δ 13.8, 21.9, 39.8, 42.3, 43.1, 44.9, 66.4, 66.8, 110.2, 157.4, 161.6, 167.6,171.8.νmax (neat): 3278, 2962, 2854, 1651, 1594, 1557, 1463, 1435, 1386, 1333, 1270, 1231, 1196, 1117, 1071, 1033, 980, 851, 829, 804, 688 cm-1. HRMS: (C13H20N4O2) [M+H]+ requires 265.1659, found [M+H]+ 265.1653. |