Phosgene → HCID 20242853, compound

HRID 483237Notes

Reaction equation

HRID 483237 reaction equation
[NH2:1][C:2]1[CH:26]=[C:25]([Cl:27])[C:24]([S:28](=[O:31])(=[O:30])[NH2:29])=[CH:23][C:3]=1[C:4]([NH:6][CH2:7][CH2:8][N:9]1[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[O:21][CH3:22])[CH2:11][CH2:10]1)=[O:5].[C:32](Cl)(Cl)=[O:33]>C(O)(=O)C.C1(C)C=CC=CC=1>[ClH:27].[Cl:27][C:25]1[CH:26]=[C:2]2[C:3]([C:4](=[O:5])[N:6]([CH2:7][CH2:8][N:9]3[CH2:14][CH2:13][N:12]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=4[O:21][CH3:22])[CH2:11][CH2:10]3)[C:32](=[O:33])[NH:1]2)=[CH:23][C:24]=1[S:28](=[O:30])(=[O:31])[NH2:29]

Participants

5

Reactant 2

HCID 6371PhosgeneHCID 13387765HCID 13387765, compound

Product 1

HCID 20242853HCID 20242853, compoundYield 26.7%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 1140TolueneSolvent

Procedure

A mixture of 7-chloro-6-sulfamoylisatoic anhydride (7.45 g) and 1-(2-aminoethyl)-4-(2-methoxyphenyl)piperazine (6.64 g) was dissolved in methanol (100 ml), and the resulting mixture was heated under reflux for 3 hours under a nitrogen stream. After completion of the reaction, the solvent was distilled off under vacuum and the residue was recrystallized from methanol-acetone and dried to give 2-amino-4-chloro-5-sulfamoyl-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]benzamide. A solution of this benzamide derivative (1.32 g) in acetic acid (20 ml) was added dropwise to a solution of phosgene (2.33 g) in toluene (10 ml) under stirring at room temperature. Then, the mixture was refluxed for one hour and cooled to room temperature. The resulting crystal was filtered and suspended in a mixture of methanol (10 ml) and water (10 ml), and after passing hydrogen chloride gas into the suspension for about 5 minutes, the solvent was distilled off under vacuum to provide a crystalline residue. It was recrystallized from water-methanol-ether to give colorless needles crystal of 7-chloro-6-sulfamoyl-3-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-2,4-(1H,3H)quinazolinedione hydrochloride (200 mg) having a m.p. of 266°-268° C. (with decomposition).

Workup

  1. temperatureThen, the mixture was refluxed for one hour
  2. temperaturecooled to room temperature
  3. filtrationThe resulting crystal was filtered
  4. additionsuspended in a mixture of methanol (10 ml) and water (10 ml)
  5. customfor about 5 minutes
  6. distillationthe solvent was distilled off under vacuum
  7. customto provide a crystalline residue
  8. customIt was recrystallized from water-methanol-ether

Sources & evidence

ORD record
ord-33a27b0e20f447c49d75a0197a458f5b
Source dataset
uspto-grants-1986_03
Patent number
US04578465

Reaction notes

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