反应详情

温度

90 °C

To a solution of N-(4-chlorobenzyl)-7-iodo-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamide (Procedure 3, 500 mg), PdCl2(PPh3)2 (21 mg), and Et3N (0.73 mL) in anhydrous DMF (3 mL) is added propargyl alcohol (0.094 mL). The mixture is heated at 90° C. for 1 h, then allowed to cool to room temperature. The reaction mixture is placed under high vacuum to remove the DMF. The resulting solid is dissolved in CH2Cl2 and washed with water. The aqueous layer is extracted with CH2Cl2 (2×). The combined organic layers are dried (Na2SO4), filtered, and condensed to afford a solid. The crude solid is adsorbed onto silica and chromatographed (1% MeOH/CH2Cl2 (1 L), 1.5% MeOH/CH2Cl2 (1 L), and 2% MeOH/CH2Cl2 (1.5 L)). Product-containing fractions are combined and concentrated to afford 243 mg (58%) of the title compound as a creme solid. Physical characteristics: m.p. 179-181° C.; 1H NMR (300 MHz, DMSO-d6) δ 9.34, 9.07, 9.00, 8.10, 7.85, 7.36, 5.50, 4.54, 4.36; IR (drift) 3294, 1676, 1632, 1618, 1561, 1541, 1521, 1490, 1353, 1335, 1131, 1061, 1040, 842, 797 cm−1; MS (ESI+) m/z 368 (M+H)+; Anal. found: C, 61.96; H, 3.69; N, 11.44.

1. temperatureto cool to room temperature
2. customto remove the DMF
3. dissolutionThe resulting solid is dissolved in CH2Cl2
4. washwashed with water
5. extractionThe aqueous layer is extracted with CH2Cl2 (2×)
6. dry with materialThe combined organic layers are dried (Na2SO4)
7. filtrationfiltered
8. customcondensed
9. customto afford a solid
10. customchromatographed (1% MeOH/CH2Cl2 (1 L), 1.5% MeOH/CH2Cl2 (1 L), and 2% MeOH/CH2Cl2 (1.5 L))
11. concentrationconcentrated