Formamide → HCID 135798749, compound

HRID 1597256Notes

Reaction equation

HRID 1597256 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH2:12][CH2:13][O:14][C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)[C:8]([O:21][CH3:22])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[CH:23](N)=O>>[CH3:22][O:21][C:8]1[CH:7]=[C:3]2[C:2](=[CH:10][C:9]=1[O:11][CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)[N:1]=[CH:23][NH:6][C:4]2=[O:5]

Participants

3

Reactant 2

HCID 713FormamideHCID 21699249HCID 21699249, compound

Product 1

HCID 135798749HCID 135798749, compoundYield 49%

Conditions

Temperature
50 °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. customprecipitated out
  2. additionWater (50 ml) was added
  3. filtrationthe solid was collected by filtration
  4. washwashed with more water and ether
  5. customdried under vacuum

Sources & evidence

ORD record
ord-24ef144fc43c42ebb4bf53a0123dbde0
Source dataset
uspto-grants-2001_09
Patent number
US06294532B1

Reaction notes

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