反应详情

温度

50 °C

To a mixture of [5-(5-ethyl-6-methoxy-2-methyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-ylmethyl]-carbamic acid tert-butyl ester (358 mg, 1.03 mmol) and sodium iodide (463 mg, 3.09 mmol) under a nitrogen atmosphere is added anhydrous acetonitrile (4 mL) followed by chlorotrimethylsilane (388 μL, 3.09 mmol). The reaction mixture is stirred at 50° C. under nitrogen for 8 hr. The black/dark brown reaction mixture is allowed to cool and then quenched with water (0.7 mL). After stirring for 20 min the mixture is evaporated. Isopropanol is added and the black suspension treated with triethylamine to give a yellow orange mixture. This crude suspension is purified by flash chromatography on a 2-gram silica gel cartridge by elution with dichloromethane:methanol (19:1 increasing to 9:1). The fractions containing the product are combined and evaporated to give an orange oil. This oil is treated with 10% trifluoroacetic acid in dichloromethane and a black mixture forms. Diethyl ether is added and the resulting suspension is filtered off to give 5-(5-aminomethyl-[1,3,4]oxadiazol-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one as its trifluoroacetic acid salt (196 mg, 55% yield) as a beige solid. LC/MS: RT: 2.10 min, m/e 235 (M+H); 1H NMR (300 MHz, d6-DMSO, δ, ppm): 12.19 (1H, s), 8.70 (3H, br.s), 7.66 (1H, s), 4.46 (2H, s), 2.58 (3H, s), 2.44 (2H, q), 1.12 (3H, t).

1. temperatureto cool
2. customquenched with water (0.7 mL)
3. stirringAfter stirring for 20 min the mixture
4. customis evaporated
5. additionIsopropanol is added
6. additionthe black suspension treated with triethylamine
7. customto give a yellow orange mixture
8. customThis crude suspension is purified by flash chromatography on a 2-gram silica gel cartridge by elution with dichloromethane:methanol (19:1 increasing to 9:1)
9. additionThe fractions containing the product
10. customevaporated
11. customto give an orange oil
12. filtrationthe resulting suspension is filtered off