Reaktion #10438

Reaktionsgleichung

2-chloro-5-fluoro-6-methylsulfanylnicotinic acid ethyl ester

cyclopropylamine

cyclopropylamine

→

title compound

Ausbeute 69.1%

2-cyclopropylamino-5-fluoro-6-methylsulfanylnicotinic acid ethyl ester

Ausbeute 69.1%

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturat reflux for 18 hours
2. 2
   workup.ADDITIONis added
3. 3
   Temperaturthe reaction mixture is refluxed for 48 hours
4. 4
   SonstigeThe solvent is removed in vacuo
5. 5
   Sonstigethe residue is partitioned between dichloromethane (250 mL) and water (100 mL)
6. 6
   WaschenThe organic layer is washed with water
7. 7
   Trocknendried (MgSO4)
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated in vacuo
10. 10
    SonstigeThe residue is chromatographed over flash grade silica gel (230–400 mesh)
11. 11
    Wascheneluting with dichloromethane

Vorschrift

A solution of 8.7 g (34.8 mmol) of 2-chloro-5-fluoro-6-methylsulfanylnicotinic acid ethyl ester (J. Med. Chem., 1993; 36:2676) and 5.7 g (100 mmol) of cyclopropylamine in 100 mL of acetonitrile is heated at reflux for 18 hours. After TLC showed the presence of unreacted starting material, 4.12 g (72 mmol) of cyclopropylamine is added and the reaction mixture is refluxed for 48 hours. The solvent is removed in vacuo and the residue is partitioned between dichloromethane (250 mL) and water (100 mL). The organic layer is washed with water, dried (MgSO4), filtered, and concentrated in vacuo. The residue is chromatographed over flash grade silica gel (230–400 mesh) eluting with dichloromethane to give 6.5 g of the title compound, mp 67–69° C.

Quelle