Reaktion #2462450

Reaktionsgleichung

Chlorosulphonic acid

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

2-ethoxyethylamine

diethylmethylamine

HCl

ether

→

title compound

Ausbeute 47.0%

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

Ausbeute 47.0%

Lösungsmittel

thionyl chloride

MeOH

MeOH

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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.

Quelle