1-Methylpiperazine → [5-(4-Methyl-piperazin-1-yl)-2-nitro-pyridin-3-yl]-acetic acid methyl ester

HRID 1992640Notes

Reaction equation

HRID 1992640 reaction equation
[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:6]([N+:12]([O-:14])=[O:13])=[N:7][CH:8]=[C:9](Br)[CH:10]=1.[CH3:16][N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1>>[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:6]([N+:12]([O-:14])=[O:13])=[N:7][CH:8]=[C:9]([N:20]2[CH2:21][CH2:22][N:17]([CH3:16])[CH2:18][CH2:19]2)[CH:10]=1

Participants

3

Reactant 2

HCID 531671-MethylpiperazineHCID 66869327(5-Bromo-2-nitro-pyridin-3-yl)-acetic acid methyl ester

Product 1

HCID 66869293[5-(4-Methyl-piperazin-1-yl)-2-nitro-pyridin-3-yl]-acetic acid methyl ester

Procedure

A mixture of (5-Bromo-2-nitro-pyridin-3-yl)-acetic acid methyl ester (472 mg, 1.72 mmol) and N-methylpiperazine (344 mg, 3.44 mmol) is heated for 18 h under an argon atmosphere. TLC analysis indicated complete consumption of starting material. The reaction mixture is cooled to RT, diluted with water and adjusted to pH 8-9 with a saturated aq. NaHCO3 solution. The aqueous phase is extracted three times with methylene chloride and the combined organic layers are washed with brine, dried over Na2SO4, and concentrated at reduced pressure. The crude product is purified by FCC (methylene chloride/MeOH 95:5 to 90:10) to afford the title compound as a yellow solid. 1H NMR (d6-DMSO 400 MHz): δ 2.01 (s, 3H), 2.22-2.26 (m, 4H), 3.24-3.28 (m, 4H), 3.40 (s, 3H), 3.81 (s, 2H), 7.26 (d, J=2 Hz, 1H), 7.97 (d, J=2 Hz, 1H). ES+−MS: 295.3 [M+H]+.

Workup

  1. temperatureis heated for 18 h under an argon atmosphere
  2. customconsumption of starting material
  3. additiondiluted with water
  4. extractionThe aqueous phase is extracted three times with methylene chloride
  5. washthe combined organic layers are washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated at reduced pressure
  8. customThe crude product is purified by FCC (methylene chloride/MeOH 95:5 to 90:10)

Sources & evidence

ORD record
ord-fff3b57910ca48e1bcfd0c02f4b23e4b
Source dataset
uspto-grants-2010_01
Patent number
US07648989B2

Reaction notes

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