Hydrochloric Acid → 2-(3-Oxo-2-thiophen-2-ylmethyl-2,3-dihydro-1H-isoindol-1-ylsulfanyl)-N-pyrimidin-2-yl-acetamide

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Reaction Steps

To a suspension of compound 15 (200 mg, 0.63 mmol) in dichloromethane (8 mL) at 0° C. was added oxalyl chloride (0.35 mL of a 2M solution in dichloromethane, 0.69 mmol) and catalytic DMF (5 drops) and the resulting reaction mixture was allowed to stir at 0 C for 10 minutes and then at room temperature for 20 minutes. Thereafter a mixture of 2-aminopyrimidine (132 mg, 1.39 mmol) and pyridine (0.11 mL, 1.39 mmol) in THF (2 mL) was added to the reaction mixture and was allowed to stir at room temperature for 4 hours. The reaction mixture was poured onto 1N HCl and extracted with ethyl acetate (3×20 mL). The combined ethyl extracts were dried over anhydrous sodium sulfate and dried in vacuo. Chromatography (SiO2, 20 to 70% EtOAc-Hexanes eluant) provided 70 mg of 16 as a white solid. (170 mg theoretical, 41% yield). 1H NMR (300 MHz, DMSO): δ 10.55 (br s, 1H), 8.5(d, J=3 Hz, 2H), 7.75-7.6(m, 3H), 7.5(m, 1H), 7.4(m, 1H), 7.2-7.05(m, 2H), 7.0-6.9(m, 1H), 5.75(s, 1H0, 5.15(d, J=15 Hz, 1H0, 4.65(d, J=15 Hz, 1H), 3.3(d, J=15 Hz, 1H), 3.1(d, J=15 Hz, 1H). MS: m/z (MH+) 397.

Provenance & Evidence