Formaldehyde → 6-Methoxy-7-(1-methylpiperidin-4-ylmethoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one

HRID 577371Notes

Reaction equation

HRID 577371 reaction equation
C=O.[C:3]([BH3-])#N.[Na+].[CH3:7][O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH2:20][CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)[N:15]=[CH:14][N:13]([CH2:27][O:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])[C:12]2=[O:35]>C1COCC1.CO>[CH3:7][O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH2:20][CH:21]1[CH2:22][CH2:23][N:24]([CH3:3])[CH2:25][CH2:26]1)[N:15]=[CH:14][N:13]([CH2:27][O:28][C:29](=[O:34])[C:30]([CH3:31])([CH3:32])[CH3:33])[C:12]2=[O:35]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 11058522(6-Methoxy-4-oxo-7-(piperidin-4-ylmethoxy)quinazolin-3(4H)-yl)methyl pivalate

Product 1

HCID 109934456-Methoxy-7-(1-methylpiperidin-4-ylmethoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-oneYield 82%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A 37% aqueous solution of formaldehyde (501 μl, 6 mmol) followed by sodium cyanoborohydride (228 mg, 3.6 mmol) were added in portions to a solution of 6-methoxy-7-(piperidin-4-ylmethoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (1.21 g, 3 mmol) in a mixture of THF/methanol (10 ml/10 ml). After stirring for 30 minutes at ambient temperature, the organic solvents were removed under vacuum and the residue was partitioned between methylene chloride and water. The organic layer was separated, washed with water and brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was triturated with ether and the resulting solid was collected by filtration, washed with ether and dried under vacuum to give 6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (1.02 g, 82%).

Workup

  1. customthe organic solvents were removed under vacuum
  2. customthe residue was partitioned between methylene chloride and water
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialdried (MgSO4)
  6. customthe volatiles were removed by evaporation
  7. customThe residue was triturated with ether
  8. filtrationthe resulting solid was collected by filtration
  9. washwashed with ether
  10. customdried under vacuum

Sources & evidence

ORD record
ord-dcaa2ef7aec74f9f92282d324041e9b8
Source dataset
uspto-grants-2015_05
Patent number
US09040548B2

Reaction notes

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