Reaction #2293179

Reaction equation

4-iodo-2-methoxynicotinic acid

tetrahydro-2H-pyran-4-ylhydrazine dihydrochloride

DIEA

EDCI hydrochloride

HOBt

→

title compound

Yield 81.2%

4-iodo-2-methoxy-N′-(tetrahydro-2H-pyran-4-yl)nicotinohydrazide

Yield 81.2%

Solvents

water

DMF

Conditions

Workup

1. 1
   Extractionthe mixture was extracted with ethyl acetate
2. 2
   WashThe organic layer was washed successively with water and saturated brine
3. 3
   Dryingdried over anhydrous sodium sulfate
4. 4
   Concentrationconcentrated under reduced pressure
5. 5
   OtherThe residue was purified by silica gel column chromatography (ethyl acetate/hexane/methanol)
6. 6
   Washthe obtained solid was washed with ethyl acetate/diisopropyl ether

Procedure

A solution of 4-iodo-2-methoxynicotinic acid (1.75 g) obtained in Step C of Example 6, tetrahydro-2H-pyran-4-ylhydrazine dihydrochloride (0.957 g), DIEA (2.2 mL), EDCI hydrochloride (1.44 g) and HOBt (1.02 g) in DMF (100 mL) was stirred overnight at room temperature. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane/methanol), and the obtained solid was washed with ethyl acetate/diisopropyl ether to give the title compound (1.55 g).

Source