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

HRID 1765082Notes

Reaction equation

HRID 1765082 reaction equation
[CH3:1][N:2]([CH3:16])[CH2:3][CH2:4][O:5][C:6]1[CH:15]=[CH:14][CH:13]=[CH:12][C:7]=1[O:8][CH2:9][CH2:10][OH:11].CC(C)([O-])C.[K+].Cl[C:24]1[C:29]([N:30]2[CH2:35][CH2:34][NH:33][CH2:32][C@H:31]2[CH3:36])=[N:28][CH:27]=[CH:26][N:25]=1>CN(C=O)C>[CH3:1][N:2]([CH3:16])[CH2:3][CH2:4][O:5][C:6]1[CH:15]=[CH:14][CH:13]=[CH:12][C:7]=1[O:8][CH2:9][CH2:10][O:11][C:24]1[C:29]([N:30]2[CH2:35][CH2:34][NH:33][CH2:32][C@H:31]2[CH3:36])=[N:28][CH:27]=[CH:26][N:25]=1

Participants

5

Reactant 3

HCID 9992195(R)-2-Chloro-3-(2-methylpiperazin-1-YL)pyrazineHCID 211066552-{2-[2-(Dimethylamino)ethoxy]phenoxy}ethanolHCID 23665647Potassium tert-butoxide

Product 1

HCID 103863332-[2-(2-[2-(Dimethylamino)ethoxy]phenoxy)ethoxy]-3-[(2R)-2-methylpiperazin-1-yl]pyrazineYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-158a6e7d631c47b69b7cd7bee3e7174d
Source dataset
uspto-grants-2007_06
Patent number
US07226925B2

Reaction notes

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