Sodium Carbonate → 8-[1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-piperidinyl]-8-azaspiro[4,5]decan-7,9-dione hydrochloride

HRID 1105671Notes

Reaction equation

HRID 1105671 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([Cl:16])[N:3]=1.[NH:17]1[CH2:22][CH2:21][CH:20]([N:23]2[C:32](=[O:33])[CH2:31][C:26]3([CH2:30][CH2:29][CH2:28][CH2:27]3)[CH2:25][C:24]2=[O:34])[CH2:19][CH2:18]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[ClH:16].[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([N:17]2[CH2:22][CH2:21][CH:20]([N:23]3[C:24](=[O:34])[CH2:25][C:26]4([CH2:30][CH2:29][CH2:28][CH2:27]4)[CH2:31][C:32]3=[O:33])[CH2:19][CH2:18]2)[N:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 902352-Chloro-6,7-dimethoxy-4-quinazolinamineHCID 128225538-(4-Piperidinyl)-8-azaspiro[4,5]decan-7,9-dione

Product 1

HCID 205562598-[1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-piperidinyl]-8-azaspiro[4,5]decan-7,9-dione hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The mixture of 70 g of 4-amino-2-chloro-6,7-dimethoxyquinazoline, 73.2 g of 8-(4-piperidinyl)-8-azaspiro[4,5]decan-7,9-dione, 62.1 g of anhydrous sodium carbonate and 800 ml of dimethylformamide is stirred under nitrogen at 135° for 8 hours. It is allowed to cool to room temperature, filtered and the filtrate evaporated. The residue is poured with stirring and cooling into 300 ml of water, the mixture diluted with 1400 ml of water and filtered. The solids are triturated with 1600 ml of ethyl acetate and 10 ml of saturated aqueous sodium carbonate. The organic layer is separated, dried, evaporated and the residue dissolved in 1,000 ml of ethyl acetate. The solution is acidified with hydrogen chloride, the precipitate filtered off and recrystallized from aqueous methanol, to yield the 8-[1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-piperidinyl]-8-azaspiro[4,5]decan-7,9-dione hydrochloride melting at 277°-279° (dec.).

Workup

  1. filtrationfiltered
  2. customthe filtrate evaporated
  3. additionThe residue is poured
  4. stirringwith stirring
  5. temperaturecooling into 300 ml of water
  6. additionthe mixture diluted with 1400 ml of water
  7. filtrationfiltered
  8. customThe solids are triturated with 1600 ml of ethyl acetate and 10 ml of saturated aqueous sodium carbonate
  9. customThe organic layer is separated
  10. customdried
  11. customevaporated
  12. dissolutionthe residue dissolved in 1,000 ml of ethyl acetate
  13. filtrationthe precipitate filtered off
  14. customrecrystallized from aqueous methanol

Sources & evidence

ORD record
ord-f3c375ba00c44156a1e6e1b778199a97
Source dataset
uspto-grants-1982_01
Patent number
US04309541

Reaction notes

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