반응 #2462450

반응 방정식

Chlorosulphonic acid

2-anilino-4-(1-ethyl-2-methylimidazol-5-yl)pyrimidine

2-ethoxyethylamine

diethylmethylamine

HCl

ether

→

title compound

수율 47.0%

4-(1-Ethyl-2-methylimidazol-5-yl)-2-{4-[N-(2-ethoxyethyl)sulphamoyl]anilino}pyrimidine

수율 47.0%

용매

thionyl chloride

MeOH

MeOH

반응 조건

후처리

1. 1
   온도then heated at 90° C. for 90 minutes
2. 2
   기타The volatiles were removed by evaporation
3. 3
   기타the residue was dried under high vacuum (<2 mmHg) for 1 hour
4. 4
   workup.STIRRINGThe mixture was stirred for 15 minutes
5. 5
   기타the volatiles were evaporated in vacuo
6. 6
   workup.ADDITIONWater (20 ml) was added
7. 7
   추출extracted DCM (2×25 ml)
8. 8
   건조DCM was dried
9. 9
   기타evaporated in vacuo
10. 10
    기타The residue was purified by flash chromatography on silica gel eluting with DCM:MeOH (100:0 increasing in polarity to 97:3)
11. 11
    기타to yield a white foam
12. 12
    기타The solvent was evaporated in vacuo
13. 13
    기타the resultant solid triturated with ether
14. 14
    여과collected by filtration and dried-under vacuum at 60° C.

실험 절차

Chlorosulphonic acid (280 μl, 4 mmol) was added dropwise to solution of 2-anilino-4-(1-ethyl-2-methylimidazol-5-yl)pyrimidine (Method 30; 279 mg, 1 mmol) in thionyl chloride (5 ml) cooled at 0° C. and the mixture stirred at 0° C. for 10 minutes then heated at 90° C. for 90 minutes. The volatiles were removed by evaporation and the residue was dried under high vacuum (<2 mmHg) for 1 hour. The resulting solid was placed under nitrogen and a solution of 2-ethoxyethylamine (356 mg, 4 mmol) and diethylmethylamine (1 ml, 15 mmol) in MeOH (3 ml) added. The mixture was stirred for 15 minutes and the volatiles were evaporated in vacuo. Water (20 ml) was added and extracted DCM (2×25 ml). DCM was dried and evaporated in vacuo. The residue was purified by flash chromatography on silica gel eluting with DCM:MeOH (100:0 increasing in polarity to 97:3) to yield a white foam. The white foam was dissolved in MeOH (3 ml) and treated with 1M HCl in ether (0.55 ml, 0.55 mmol). The solvent was evaporated in vacuo and the resultant solid triturated with ether, collected by filtration and dried-under vacuum at 60° C. to yield the title compound (128 mg, 47%) as a yellow solid. NMR: 1.05 (t, 3H), 1.30 (t, 3H), 2.76 (s, 3H), 2.88 (m, 2H), 3.32 (m, 4H), 4.76 (m, 2H), 7.37 (d, 1H), 7.52 (m, 1H), 7.73 (d, 2H), 7.90 (d, 2H), 8.43 (s, 1H), 8.65 (d, 1H), 10.14 (brs, 1H); m/z 431.

출처