Reaction #645479

Reaction equation

alcohol

3-{[3,5-Diethyl-1-(2-hydroxyethyl)-1H-pyrazol-4-yl]oxy}-5-methoxybenzonitrile

triphenylphosphine

phthalimide

diisopropylazodicarboxylate

hydrazine hydrate

→

title compound

Yield 152.2%

3-{[1-(2-Aminoethyl)-3,5-diethyl-1H-pyrazol-4-yl]oxy}-5-methoxybenzonitrile

Yield 152.2%

ammonia

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   workup.ADDITIONwas added dropwise
2. 2
   OtherThe solvent was removed under reduced pressure
3. 3
   workup.DISSOLUTIONthe residue was dissolved in ethanol (6 ml)
4. 4
   workup.STIRRINGThe slurry was stirred for 48 hours at room temperature under nitrogen
5. 5
   Concentrationconcentrated under reduced pressure
6. 6
   workup.DISSOLUTIONthe residue was dissolved in methanol
7. 7
   Washeluting with methanol
8. 8
   Otherto remove impurities
9. 9
   Wash2M ammonia in methanol solution to elute the product
10. 10
    OtherThe product was then purified by flash chromatography on silica gel eluting with dichloromethane:methanol (95:5)

Procedure

The alcohol from Example 202 (87 mg, 0.28 mmol), triphenylphosphine (220 mg, 0.84 mmol) and phthalimide (124 mg, 0.84 mmol) were dissolved in tetrahydrofuran (5 ml) at 0° C. under nitrogen and diisopropylazodicarboxylate (165 μl, 0.84 mmol) dissolved in tetrahydrofuran (1 ml) was added dropwise. The reaction was allowed to warm to room temperature and was stirred for 18 hours. The solvent was removed under reduced pressure, the residue was dissolved in ethanol (6 ml) and hydrazine hydrate (68 μl, 1.40 mmol) was added. The slurry was stirred for 48 hours at room temperature under nitrogen, concentrated under reduced pressure and the residue was dissolved in methanol. The solution was then passed through an SCX column eluting with methanol to remove impurities, then 2M ammonia in methanol solution to elute the product. The product was then purified by flash chromatography on silica gel eluting with dichloromethane:methanol (95:5) then dichloromethane:methanol:0.88 ammonia (90:10:1, by volume) to provide the title compound (67 mg) as an oil.

Source