反応 #2286385

反応方程式

2-(methylthio)ethanamine

[2-(5-fluoropyridin-3-yl)-thiazol-5-yl]-methyl-amine

phosgene

→

desired product

収率 81.0%

[2-(5-fluoropyridin-3-yl)-thiazol-5-yl]-1-methyl-3-(2-methylsulfanyl-ethyl)urea

収率 81.0%

溶媒

DCE

反応条件

後処理

1. 1
   その他the ice bath was removed
2. 2
   workup.WAITAfter another 5 min
3. 3
   温度the mixture was heated
4. 4
   温度to reflux
5. 5
   その他The reaction was capped
6. 6
   温度heated at 80° C. overnight
7. 7
   その他The reaction was quenched upon addition of ethyl acetate and 0.1 N HCl
8. 8
   その他The layers were separated
9. 9
   洗浄the organic layer was washed separately with saturated aqueous NaHCO3 and brine
10. 10
    乾燥The ethyl acetate layer was dried over MgSO4
11. 11
    ろ過filtered
12. 12
    濃縮concentrated under reduced pressure
13. 13
    その他The crude product was purified by silica gel column chromatography (0 to 100% ethyl acetate/hexanes)

実験手順

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).

出典