(R)-2-Chloro-3-(2-methylpiperazin-1-YL)pyrazine → 2-[2-(2-[2-(Dimethylamino)ethoxy]phenoxy)ethoxy]-3-[(2R)-2-methylpiperazin-1-yl]pyrazine

To a solution of 2-{2-[2-(dimethylamino)ethoxy]phenoxy}ethanol (from Step 3; 0.82 g, 3.6 mmol) in dry DMF (25 mL) was added potassium tert-butoxide (0.59 g, 5.3 mmol) and the mixture was stirred at room temperature for 10 minutes. To the mixture was added 2-chloro-3-[(2R)-2-methylpiperazin-1-yl]pyrazine* (0.70 g, 3.3 mmol) in DMF (5 mL) in one portion and the reaction mixture was stirred at 55° C. for 2 h. A small spoon of silica was added, the solvent was filtered off and the solvent was evaporated under reduced pressure. The crude product was purified on a column of silica (100 mm, i.d.=30 mm) with CHCl3/MeOH/NH4OH (95:5:0.2; 100 mL, followed by 90:10:0.2) as eluent to give 0.80 g (60%) of the title compound as a light brown oil. HRMS m/z calcd for C21H31N5O3 (M)+ 401.2427. found 401.2414. *Reported in WO 00/76984, Example 192, Step 2.

1. stirringthe reaction mixture was stirred at 55° C. for 2 h
2. additionA small spoon of silica was added
3. filtrationthe solvent was filtered off
4. customthe solvent was evaporated under reduced pressure
5. customThe crude product was purified on a column of silica (100 mm, i.d.=30 mm) with CHCl3/MeOH/NH4OH (95:5:0.2; 100 mL, followed by 90:10:0.2) as eluent

ORDレコード

ord-158a6e7d631c47b69b7cd7bee3e7174d

出典データセット

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07226925B2