反应详情

温度

5 °C

To a dry 500 ml round bottom flask equipped with magnetic stirrer, thermometer, and nitrogen inlet was charged N-ethyl-2-(pyridin-3-yl)thiazol-5-amine (5.1 g, 25 mmol), diethyl ether (200 mL) and dioxane (5 mL). The resulting suspension (not all solid dissolved) was cooled to 5° C., and N-chlorosuccinamide (3.65 g, 27.3 mmol) was added portionwise. After all of the chlorinating agent was added, a brown solid precipitated from solution. The reaction mixture was stirred at 5° C. for 60 minutes, then analyzed by HPLC(YMC AQ column 5% ACN 95% water-0.05% TFA to 95% ACN 5% water with 0.05% TFA over 20 Min @ 1.0 ml/min). HPLC analysis showed no starting material and one major product consistent with the desired chloride. The brown suspension was filtered through a pad of Celite®, and the Celite® pad rinsed with diethyl ether (˜20 mL). The filtrate was cooled to 5° C. and acidified with stirring by the addition of 6.5 ml of 4M HCl in dioxane. A yellow solid immediately formed. The solid was collected by vacuum filtration, rinsed with diethyl ether, and dried in vacuo at 40° C. for 2 hours. This gave 4-chloro-N-ethyl-2-(pyridin-3-yl)thiazol-5-amine hydrochloride as a yellow solid (6.3 g, 92%): mp 180-182° C.; 1H NMR (400 MHz, DMSO-d6) δ 9.07 (d, J=2.0 Hz, 1H), 8.70 (dd, J=5.4, 1.3 Hz, 1H), 8.59-8.42 (m, 1H), 7.86 (dd, J=8.2, 5.3 Hz, 1H), 5.27 (s, 5H), 3.20 (q, J=7.2 Hz, 2H), 1.23 (t, J=7.1 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 148.10, 140.19, 138.58, 137.91, 137.01, 132.06, 127.30, 115.89, 43.43, 13.87; Anal. Calcd. for C10H11Cl2N3S: C, 43.49; H, 4.01; Cl, 25.67; N, 15.21; S, 11.61. Found: C, 43.42: H, 4.01; Cl, 25.55; N, 14.99; S, 11.46.

1. customTo a dry 500 ml round bottom flask equipped with magnetic stirrer
2. dissolutionThe resulting suspension (not all solid dissolved)
3. additionAfter all of the chlorinating agent was added
4. customa brown solid precipitated from solution
5. filtrationThe brown suspension was filtered through a pad of Celite®
6. washthe Celite® pad rinsed with diethyl ether (˜20 mL)
7. temperatureThe filtrate was cooled to 5° C.
8. stirringwith stirring by the addition of 6.5 ml of 4M HCl in dioxane
9. customA yellow solid immediately formed
10. filtrationThe solid was collected by vacuum filtration
11. washrinsed with diethyl ether
12. customdried in vacuo at 40° C. for 2 hours