Hydrochloric Acid → Methyl [5-(4-nitrobenzyl)imidazo[1,2-c]pyrimidin-8-yl]acetate

HRID 2353324Notes

Reaction equation

HRID 2353324 reaction equation
CO[CH:3](OC)[CH2:4][NH:5][C:6]1[C:11]([CH2:12][C:13]([O:15][CH3:16])=[O:14])=[CH:10][N:9]=[C:8]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=2)[N:7]=1.Cl>O1CCOCC1>[N+:24]([C:21]1[CH:22]=[CH:23][C:18]([CH2:17][C:8]2[N:7]3[CH:3]=[CH:4][N:5]=[C:6]3[C:11]([CH2:12][C:13]([O:15][CH3:16])=[O:14])=[CH:10][N:9]=2)=[CH:19][CH:20]=1)([O-:26])=[O:25]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 57542083Methyl [4-[(2,2-dimethoxyethyl)amino]-2-(4-nitrobenzyl)pyrimidin-5-yl]acetate

Product 1

HCID 57542081Methyl [5-(4-nitrobenzyl)imidazo[1,2-c]pyrimidin-8-yl]acetateYield 3.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A solution of methyl [4-[(2,2-dimethoxyethyl)amino]-2-(4-nitrobenzyl)pyrimidin-5-yl]acetate (1.00 g, 2.56 mmol) and HCl (1.0 M in water, 3.84 mL, 3.85 mmol) in dioxane (10 mL) was stirred at 85° C. for 1 hour. After the removal of the solvent in vacuo, water was added to the residue. The aqueous solution was neutralized by 1M NaOH and extracted with ethyl acetate. The extracts were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. To the resulting crude product was added phosphorus oxychloride (1.4 mL) and the mixture was stirred at 85° C. for 3 hours. After the removal of the excess phosphorus oxychloride, the residue was dissolved with ethyl acetate. The organic layer was washed with water, sat.NaHCO3 and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica-gel, (chloroform:methanol, 98/2) to give methyl [5-(4-nitrobenzyl)imidazo[1,2-c]pyrimidin-8-yl]acetate (28 mg, 3%) as brown oil.

Workup

  1. customAfter the removal of the solvent in vacuo, water
  2. additionwas added to the residue
  3. extractionextracted with ethyl acetate
  4. washThe extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. additionTo the resulting crude product was added phosphorus oxychloride (1.4 mL)
  9. customAfter the removal of the excess phosphorus oxychloride
  10. dissolutionthe residue was dissolved with ethyl acetate
  11. washThe organic layer was washed with water
  12. dry with materialNaHCO3 and brine, dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe crude product was purified by column chromatography on silica-gel, (chloroform:methanol, 98/2)

Sources & evidence

ORD record
ord-ace8d38aa0a5496999c3403deb9bb30a
Source dataset
uspto-grants-2010_07
Patent number
US07750014B2

Reaction notes

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