Hydrogen Bromide → 8-Chloro-1,2,3,4-tetrahydro-1-methyl-2,4-dioxo-3-(4-piperidinyl)quinazoline hydrobromide

HRID 55019Notes

Reaction equation

HRID 55019 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]([CH3:12])[C:9](=[O:13])[N:8]([CH:14]1[CH2:19][CH2:18][N:17](C(OCC)=O)[CH2:16][CH2:15]1)[C:7]2=[O:25].[BrH:26]>>[BrH:26].[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]([CH3:12])[C:9](=[O:13])[N:8]([CH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)[C:7]2=[O:25]

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 229234358-Chloro-3-(1-ethoxycarbonyl-4-piperidinyl)-1,2,3,4-tetrahydro-1-methyl-2,4-dioxoquinazoline

Product 1

HCID 229233978-Chloro-1,2,3,4-tetrahydro-1-methyl-2,4-dioxo-3-(4-piperidinyl)quinazoline hydrobromide

Procedure

In 10 ml of 48% hydrobromic acid was dissolved 451.8 mg (1.24 mmol) of 8-chloro-3-(1-ethoxycarbonyl-4-piperidinyl)-1,2,3,4-tetrahydro-1-methyl-2,4-dioxoquinazoline (Compound a) obtained in Reference Example 7, and the solution was heated under reflux for 1 hour. After the solvent was distilled off, ethanol was added to the residue, and the precipitated crystals were collected by filtration to give 119.5 mg of crude 8-chloro-1,2,3,4-tetrahydro-1-methyl-2,4-dioxo-3-(4-piperidinyl)quinazoline hydrobromide. The crude product was dissolved in 10 ml of DMF, and 65 mg (0.29 mmol) of 4-chloro-6,7-dimethoxyquinazoline and 122 mg (0.87 mmol) of potassium carbonate were added thereto, followed by heating at 120° C. for 2 hours. To the reaction mixture were added water and dilute hydrochloric acid for neutralization, and the mixture was extracted with chloroform. The organic layer was washed with an aqueous solution of sodium chloride and dried. The solvent was distilled off, and the residue was purified by silica gel column chromatography (eluent: chloroform/methanol=50/1). Ethyl acetate and ether were added to the product, and the precipitated crystals were collected by filtration and washed with ether to give 55.2 mg (yield: 8.9%) of Compound 15 as white crystals.

Workup

  1. customobtained in Reference Example 7
  2. temperaturethe solution was heated
  3. temperatureunder reflux for 1 hour
  4. distillationAfter the solvent was distilled off
  5. additionethanol was added to the residue
  6. filtrationthe precipitated crystals were collected by filtration

Sources & evidence

ORD record
ord-34a20ffd02ec493080d655c32af02592
Source dataset
uspto-grants-1997_04
Patent number
US05624926

Reaction notes

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