Acetic Acid → 5-Bromo-N-[5-[2-methoxy-6-[(4-methoxyphenyl)methoxy]phenyl]-1H-pyrazol-3-yl]-2-pyrazinamine

Temperature

-78 °C

5-Bromopyrazin-2-amine (3.73 g, 21.4 mmol) is dissolved in THF (30 mL) and cooled to −78° C. A solution of n-butyllithium in hexane (10.32 mL, 23.5 mmol) is added slowly. The reaction mixture is stirred at low temperature for 15 min and then warmed slowly to room temperature and stirred an additional one hour. The mixture is recooled to 0° C. and a solution of 1-(2-methoxy-6-(4-methoxybenzyloxy)phenyl)-3,3-bis(methylthio)prop-2-en-1-one (8.39 g, 21.4 mmol) in THF (50 mL) is added via cannula. The solution becomes homogenous and is stirred 15 min at room temperature before being heated to reflux for 10 h. The solution is then cooled to room temperature and the solvent is removed under reduced pressure. The solid residue is dissolved in EtOH (150 mL) and glacial acetic acid (1.3 mL, 23.5 mmol) is added. Hydrazine hydrate (5.25 mL, 107 mmol) is added and the solution is refluxed an additional 8 h. The mixture is cooled to room temperature and concentrated under vacuum. The product is purified by silica gel chromatography (CH2Cl2/MeOH) to give 5.76 g (74%) of a brown solid.

1. temperaturewarmed slowly to room temperature
2. stirringstirred an additional one hour
3. customis recooled to 0° C.
4. stirringis stirred 15 min at room temperature
5. temperaturebefore being heated
6. temperatureto reflux for 10 h
7. temperatureThe solution is then cooled to room temperature
8. customthe solvent is removed under reduced pressure
9. dissolutionThe solid residue is dissolved in EtOH (150 mL)
10. temperaturethe solution is refluxed an additional 8 h
11. temperatureThe mixture is cooled to room temperature
12. concentrationconcentrated under vacuum
13. customThe product is purified by silica gel chromatography (CH2Cl2/MeOH)

ORD record

ord-d5f813e5d5554124866717833eac822c

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08314108B2