반응 #10438

반응 방정식

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

cyclopropylamine

cyclopropylamine

→

title compound

수율 69.1%

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

수율 69.1%

용매

acetonitrile

반응 조건

후처리

1. 1
   온도at reflux for 18 hours
2. 2
   workup.ADDITIONis added
3. 3
   온도the reaction mixture is refluxed for 48 hours
4. 4
   기타The solvent is removed in vacuo
5. 5
   기타the residue is partitioned between dichloromethane (250 mL) and water (100 mL)
6. 6
   세척The organic layer is washed with water
7. 7
   건조dried (MgSO4)
8. 8
   여과filtered
9. 9
   농축concentrated in vacuo
10. 10
    기타The residue is chromatographed over flash grade silica gel (230–400 mesh)
11. 11
    세척eluting with dichloromethane

실험 절차

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.

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