1-Methylpiperazine → Methyl 6-(4-methylpiperazin-1-yl)pyridine-3-carboxylate

HRID 1677099Notes

Reaction equation

HRID 1677099 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[CH3:12][N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH3:9][O:8][C:6](=[O:7])[C:5]1[CH:10]=[CH:11][C:2]([N:16]2[CH2:17][CH2:18][N:13]([CH3:12])[CH2:14][CH2:15]2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 531671-MethylpiperazineHCID 81531DiisopropylethylamineHCID 254249Methyl 6-chloropyridine-3-carboxylate

Product 1

HCID 9859497Methyl 6-(4-methylpiperazin-1-yl)pyridine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Methyl 6-chloronicotinate (5.0 g) was dissolved in DMF (75 ml) at r.t. under an argon atmosphere. 1-Methylpiperazine (3.66 ml) and diisopropylethylamine (30.7 ml) were added and the solution was stirred for 5 hours at 80° C. The reaction was quenched with water. The solution was extracted with EtOAc. The water phase was twice washed with EtOAc. The combined organic layers were washed with water and sat. aq. NaCl, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 9:1) to give 6-(4-methyl-piperazin-1-yl)-nicotinic acid methyl ester (5.59 g) as light yellow solid.

Workup

  1. customThe reaction was quenched with water
  2. extractionThe solution was extracted with EtOAc
  3. washThe water phase was twice washed with EtOAc
  4. washThe combined organic layers were washed with water and sat. aq. NaCl
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record
ord-ac3a4cef8fe547e393ceabd359615e0c
Source dataset
uspto-grants-2011_08
Patent number
US08008305B2

Reaction notes

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