HCID 21699281, compound → HCID 21699249, compound

HRID 1597255Notes

Reaction equation

HRID 1597255 reaction equation
[CH3:1][O:2][C:3]1[C:4]([O:15][CH2:16][CH2:17][O:18][C:19]2[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=2)=[CH:5][C:6]([N+:12]([O-])=O)=[C:7]([CH:11]=1)[C:8]([NH2:10])=[O:9]>[Pd].CO>[NH2:12][C:6]1[CH:5]=[C:4]([O:15][CH2:16][CH2:17][O:18][C:19]2[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=2)[C:3]([O:2][CH3:1])=[CH:11][C:7]=1[C:8]([NH2:10])=[O:9]

Participants

4

Reactant 1

HCID 21699281HCID 21699281, compound

Product 1

HCID 21699249HCID 21699249, compoundYield 100.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

5-Methoxy-2-nitro-4-(2-(4-pyridyloxy)ethoxy)benzamide (2.15 g, 6.4 mmol) and 10% palladium-on-charcoal catalyst (100 mg) were suspended in methanol (400 ml) and placed under hydrogen at atmospheric pressure. The reaction mixture was heated at 40° C. for 1 hour, cooled to ambient temperature, filtered through diatomaceous earth and the solvent was removed by evaporation. The precipitate was slurried with ether and collected by filtration to give 2-amino-5-methoxy-4-(2-(4-pyridyloxy)ethoxy)benzamide as a cream solid (1.95 g, 99%). 2-Amino-5-methoxy-4-(2-(4-pyridyloxy)ethoxy)benzamide (1.95 g, 6.4 mmol) and formamide (10 ml) were heated at 190-200° C. for 1 hour. The reaction mixture was allowed to cool to 50° C. as the product precipitated out. Water (50 ml) was added and the solid was collected by filtration, washed with more water and ether and dried under vacuum to give 6-methoxy-7-(2-(4-pyridyloxy)ethoxy)-3,4-dihydroquinazolin-4-one (0.99 g, 49%) as a cream solid. The 6-methoxy-7-(2-(4-pyridyioxy)ethoxy)-3,4-dihydroquinazolin-4-one (312 mg, 1 mmol) was heated at reflux in thionyl chloride (10 ml) and DMF (5 drops) for 1 hour, then evaporated to dryness and partitioned between a saturated solution of sodium hydrogen carbonate and methylene chloride. The methylene chloride phase was dried by filtration through a phase separator paper and the solvent was removed by evaporation to give crude 4-chloro-6-methoxy-7-(2-(4-pyridyloxy)ethoxy)quinazoline which was used without further purification.

Workup

  1. temperaturecooled to ambient temperature
  2. filtrationfiltered through diatomaceous earth
  3. customthe solvent was removed by evaporation
  4. filtrationcollected by filtration

Sources & evidence

ORD record
ord-b553cba2dfad4cb9a126e5801eb5b90f
Source dataset
uspto-grants-2001_09
Patent number
US06294532B1

Reaction notes

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