Sodium Carbonate → 2-[1-(4-Amino-6,7,8-trimethoxy-2-quinazolinyl)-4-piperidinyl]-isoindolin-1-one monohydrochloride

HRID 1105677Notes

Reaction equation

HRID 1105677 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([O:16][CH3:17])[C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([Cl:18])[N:3]=1.[NH:19]1[CH2:24][CH2:23][CH:22]([N:25]2[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26]2=[O:34])[CH2:21][CH2:20]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[ClH:18].[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([O:16][CH3:17])[C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([N:19]2[CH2:24][CH2:23][CH:22]([N:25]3[CH2:33][C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[C:26]3=[O:34])[CH2:21][CH2:20]2)[N:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 30158042-Chloro-6,7,8-trimethoxyquinazolin-4-amineHCID 154319612-(Piperidin-4-yl)isoindolin-1-one

Product 1

HCID 205562492-[1-(4-Amino-6,7,8-trimethoxy-2-quinazolinyl)-4-piperidinyl]-isoindolin-1-one monohydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The mixture of 5.39 g of 4-amino-2-chloro-6,7,8-trimethoxy-quinazoline, 4.32 g of 2-(4-piperidinyl)-isoindolin-1-one, 4.24 g of anhydrous sodium carbonate and 75 ml of dimethylformamide is stirred under nitrogen at 125°-130° for 16 hours. It is filtered, the filtrate evaporated, the residue dissolved in methylene chloride and the solution washed with aqueous sodium bicarbonate. The organic layer is separated, dried, and evaporated. The residue is suspended in refluxing isopropanol and acidified with hydrogen chloride to pH=1. The precipitate formed is filtered off and triturated with warm ethanol to yield the 2-[1-(4-amino-6,7,8-trimethoxy-2-quinazolinyl)-4-piperidinyl]-isoindolin-1-one monohydrochloride melting at 234° (dec.).

Workup

  1. filtrationIt is filtered
  2. customthe filtrate evaporated
  3. dissolutionthe residue dissolved in methylene chloride
  4. washthe solution washed with aqueous sodium bicarbonate
  5. customThe organic layer is separated
  6. customdried
  7. customevaporated
  8. temperaturein refluxing isopropanol
  9. customThe precipitate formed
  10. filtrationis filtered off
  11. customtriturated with warm ethanol

Sources & evidence

ORD record
ord-3e3493160f39465db3bdb48b3146e18c
Source dataset
uspto-grants-1982_01
Patent number
US04309541

Reaction notes

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