Reaction #168092

Reaction equation

2-chloropropane

4-[6-(4-Trifluoromethylphenyl)pyridazin-3-yl][1,4]diazepane, dihydrochloride

triethylamine

Sodium hydride

→

title compound

Yield 21.0%

1-Isopropyl-4-[6-(4-trifluoromethylphenyl)pyridazin-3-yl]-[1,4]diazepane, dihydrochloride

Yield 21.0%

Solvents

N,N-dimethylformamide

THF

Conditions

Workup

1. 1
   Temperaturethe reaction mixture was heated 30 min at 160° C. and 30 min at 180° C. in a microwave oven
2. 2
   OtherThe reaction mixture was purified on a silicagel column (0.04-0.063 mesh)
3. 3
   OtherThis afforded a crude oil
4. 4
   workup.ADDITIONcontaining several components that
5. 5
   Otherwas purified further by preparative HPLC
6. 6
   workup.DISSOLUTIONThis afforded 9 mg of an oil which was dissolved into MeOH
7. 7
   workup.ADDITIONAddition of HCl in diethyl ether

Procedure

4-[6-(4-Trifluoromethylphenyl)pyridazin-3-yl][1,4]diazepane, dihydrochloride (0.028 g, 0.071 mmol) was suspended in THF (4 mL) and triethylamine (0.022 g, 0.21 mmol) was added. Sodium hydride (0.0085 g, 0.35 mmol) was added and the reaction mixture was stirred at rt for 20 min. Dry N,N-dimethylformamide (1 mL) and 2-chloropropane (0.056 g, 0.71 mmol) was added and the reaction mixture was heated 30 min at 160° C. and 30 min at 180° C. in a microwave oven. The reaction mixture was purified on a silicagel column (0.04-0.063 mesh) using dichloromethane/MeOH (9:1) as eluent. This afforded a crude oil containing several components that was purified further by preparative HPLC using Method B. This afforded 9 mg of an oil which was dissolved into MeOH. Addition of HCl in diethyl ether afforded 6.5 mg (21%) of the title compound as an oily dihydrochloride.

Source