3-Methoxybenzaldehyde → 3-[1-(3-methoxybenzyl)piperidin-4-yl]-4-(3-hydroxyphenyl)-3,4-dihydro-2(1H)-quinazolinone

HRID 743070Notes

Reaction equation

HRID 743070 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:38]=[CH:39][CH:40]=1)[CH2:6][N:7]1[CH2:12][CH2:11][CH:10]([N:13]2[CH:22]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29]CC4C=CC=CC=4)[CH:24]=3)[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[NH:15][C:14]2=[O:37])[CH2:9][CH2:8]1.C([O-])=O.[NH4+].C(=O)C1C=CC=C(OC)C=1.C([BH3-])#N.[Na+]>CO.[C].[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:38]=[CH:39][CH:40]=1)[CH2:6][N:7]1[CH2:12][CH2:11][CH:10]([N:13]2[CH:22]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([OH:29])[CH:24]=3)[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[NH:15][C:14]2=[O:37])[CH2:9][CH2:8]1

Participants

7

Reactant 4

HCID 115693-MethoxybenzaldehydeHCID 2723923Ammonium formateHCID 5003444Sodium cyanoborohydrideHCID 19423617HCID 19423617, compound

Product 1

HCID 194235903-[1-(3-methoxybenzyl)piperidin-4-yl]-4-(3-hydroxyphenyl)-3,4-dihydro-2(1H)-quinazolinoneYield 75%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 887MethanolSolvent

Procedure

To a solution of 1.3 g (2.44 mmol) of 3-[1-(3-methoxybenzyl)piperidin-4-yl]-4-(3-benzyloxyphenyl)-3,4-dihydro-2(1H)-quinazolinone in 100 mL of methanol were added 504 mg (8 mmol) of ammonium formate and 50 mg of 10 palladium-carbon, and the mixture was heated under reflux for 8 hours. After being cooled, the reaction mixture was filtered through cerite, and the filtrate was concentrated in vacuo. The residue was dissolved in 50 mL of methanol, and 1.33 g (9.76 mmol) of m-anisaldehyde and 613 mg (9.76 mmol) of sodium cyanoborohydride were added to the solution. The mixture was stirred for 12 hours at ambient temperature. The reaction mixture was concentrated in vacuo, diluted with water, then adjusted to pH 10 with aqueous ammonia and extracted with chloroform. The organic layer separated was dried on potassium carbonate and concentrated in vacuo. The residue was purified by means of column chromatography (silica gel, 1:9 methanol:chloroform) to give 810 mg (1.83 mmol) of the title compound.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 8 hours
  3. temperatureAfter being cooled
  4. filtrationthe reaction mixture was filtered through cerite, and the filtrate
  5. concentrationwas concentrated in vacuo
  6. dissolutionThe residue was dissolved in 50 mL of methanol
  7. concentrationThe reaction mixture was concentrated in vacuo
  8. additiondiluted with water
  9. extractionextracted with chloroform
  10. customThe organic layer separated
  11. customwas dried on potassium carbonate
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by means of column chromatography (silica gel, 1:9 methanol:chloroform)

Sources & evidence

ORD record
ord-fa7fb2dbdc7246deb27ad9b0665b8366
Source dataset
uspto-grants-1996_09
Patent number
US05556860

Reaction notes

Loading…