تفاعل #2286385
ord-534eff04a8394a7ab5e03bf1f632bebc
معادلة التفاعل
المذيبات
ظروف التفاعل
المعالجة
- 1أخرىthe ice bath was removed
- 2workup.WAITAfter another 5 min
- 3درجة الحرارةthe mixture was heated
- 4درجة الحرارةto reflux
- 5أخرىThe reaction was capped
- 6درجة الحرارةheated at 80° C. overnight
- 7أخرىThe reaction was quenched upon addition of ethyl acetate and 0.1 N HCl
- 8أخرىThe layers were separated
- 9غسيلthe organic layer was washed separately with saturated aqueous NaHCO3 and brine
- 10تجفيفThe ethyl acetate layer was dried over MgSO4
- 11ترشيحfiltered
- 12تركيزconcentrated under reduced pressure
- 13أخرىThe crude product was purified by silica gel column chromatography (0 to 100% ethyl acetate/hexanes)
الإجراء التجريبي
To a solution of [2-(5-fluoropyridin-3-yl)-thiazol-5-yl]-methyl-amine (0.4 g, 1.91 mmol) in DCE (5 mL) at 0° C. was added phosgene (1.3 mL, 2.5 mmol, 20 wt % solution in toluene). After 5 min, DMAP (0.5 g, 4.1 mmol) was added in one portion and the ice bath was removed. After another 5 min, the mixture was heated to reflux and stirred for 20 min. The reaction was cooled to ambient temperature and half of the solution was transferred to a vial and to this was added 2-(methylthio)ethanamine (0.183 g, 2.0 mmol) and DMAP (0.244 g, 2.0 mmol). The reaction was capped and heated at 80° C. overnight. The reaction was quenched upon addition of ethyl acetate and 0.1 N HCl. The layers were separated, and the organic layer was washed separately with saturated aqueous NaHCO3 and brine. The ethyl acetate layer was dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (0 to 100% ethyl acetate/hexanes) to give the desired product as an off-white solid (0.253 g, 81%): mp 117-119° C.; 1H NMR (300 MHz, CDCl3) δ 8.94 (br s, 1H), 8.50 (d, J=2.7 Hz, 1H), 7.99-7.94 (m, 1H), 7.54 (s, 1H), 5.37 (m, 1H), 3.53 (q, J=11.8, 5.5 Hz, 2H), 3.43 (s, 3H), 2.72 (app t, J=6.6 Hz, 2H), 2.13 (s, 3H); ESIMS m/z 327.1 (M+H); m/z 325.0 (M−1).