Hydrochloric Acid → 3-[1-(6-Ethoxy-7-hydroxy-2-morpholino-4-quinazolinyl)-4-piperidinyl]-1,2,3,4-tetrahydro-1,6-dimethyl-2,4-dioxoquinazoline

HRID 617157Notes

Reaction equation

HRID 617157 reaction equation
[H-].[Na+].C1(S)C=CC=CC=1.Cl.[CH2:11]([O:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:23]=1[O:24]CC)[N:20]=[C:19]([N:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1)[N:18]=[C:17]2[N:33]1[CH2:38][CH2:37][CH:36]([N:39]2[C:48](=[O:49])[C:47]3[C:42](=[CH:43][CH:44]=[C:45]([CH3:50])[CH:46]=3)[N:41]([CH3:51])[C:40]2=[O:52])[CH2:35][CH2:34]1)[CH3:12].Cl>CN(C=O)C.O>[CH2:11]([O:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:23]=1[OH:24])[N:20]=[C:19]([N:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1)[N:18]=[C:17]2[N:33]1[CH2:38][CH2:37][CH:36]([N:39]2[C:48](=[O:49])[C:47]3[C:42](=[CH:43][CH:44]=[C:45]([CH3:50])[CH:46]=3)[N:41]([CH3:51])[C:40]2=[O:52])[CH2:35][CH2:34]1)[CH3:12]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7969ThiophenolHCID 24758Sodium hydrideHCID 99388233-[1-(6,7-Diethoxy-2-morpholino-4-quinazolinyl)-4-piperidinyl]-1,2,3,4-tetrahydro-1,6-dimethyl-2,4-dioxoquinazoline hydrochloride

Product 1

HCID 1358228343-[1-(6-Ethoxy-7-hydroxy-2-morpholino-4-quinazolinyl)-4-piperidinyl]-1,2,3,4-tetrahydro-1,6-dimethyl-2,4-dioxoquinazolineYield 49%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

In 10 ml of DMF was suspended 1.19 g (30.0 mmol) of 60% sodium hydride, and 3.07 ml (30.0 mmol) of thiophenol in 20 ml of DMF was dropwised under ice-cooling. After the mixture was stirred at ice-cooling for 10 minutes, 5.74 g (10.0 mmol) of Compound 10 obtained in Example 10 in DMF (50 ml) was added at ice-cooling, then the reaction mixture was stirred at 150° C. for 20 hours. After the reaction mixture was cooled to room temperature, water was added, pH of the reaction mixture was adjusted at 5 by concentrated hydrochloric acid and was subjected to extraction with chloroform. The organic layer was washed with sodium chloride solution and dried, concentrated to give residue which was purified by silica gel column chromatography (eluent: chloroform/methanol=50/1). The more polar product obtained was recrystallized from ethanol/ether to give 2.67 g (yield: 49%) of Compound 47 as white crystals.

Workup

  1. temperaturecooling
  2. temperaturecooling for 10 minutes
  3. temperaturecooling
  4. stirringthe reaction mixture was stirred at 150° C. for 20 hours
  5. extractionwas subjected to extraction with chloroform
  6. washThe organic layer was washed with sodium chloride solution
  7. customdried
  8. concentrationconcentrated
  9. customto give residue which
  10. customwas purified by silica gel column chromatography (eluent: chloroform/methanol=50/1)
  11. customThe more polar product obtained
  12. customwas recrystallized from ethanol/ether

Sources & evidence

ORD record
ord-5199e45a13c646aeb680c0b3843f27de
Source dataset
uspto-grants-1999_09
Patent number
US05948784

Reaction notes

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