Formaldehyde → 8-Chloro-6-(2-fluorophenyl)-3-morpholino-4H-imidazo[1,5-a][1,4]benzodiazepine 5-oxide

HRID 1389431Notes

Reaction equation

HRID 1389431 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][CH:10]([C:12]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[N:13]O)[CH2:9][N+:8]([O-:21])=[C:7]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[F:28])[C:6]=2[CH:29]=1.C=O.O.[C:33]1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:33]=[N:13][C:12]([N:15]4[CH2:16][CH2:17][O:18][CH2:19][CH2:20]4)=[C:10]3[CH2:9][N+:8]([O-:21])=[C:7]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[F:28])[C:6]=2[CH:29]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 521998p-Toluenesulfonic acid monohydrateHCID 178526225HCID 178526225, compound

Product 1

HCID 130469878-Chloro-6-(2-fluorophenyl)-3-morpholino-4H-imidazo[1,5-a][1,4]benzodiazepine 5-oxide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 3 g (7.1 mmole) of 7-chloro-5-(2-fluorophenyl)-2,3-dihydro-N-hydroxy-α-(4-morpholinyl)-1H-1,4-benzodiazepine-2-methanimine 4-oxide, 0.6 g (20 mmole) of paraformaldehyde, 100 ml of ethanol and 250 mg of paratoluene sulfonic acid hydrate was heated to reflux for 16 hours. The crude product obtained after the usual workup was chromatographed over 60 g of silica gel using 5% (v/v) of ethanol in methylene chloride for elution. The clean fractions of product were combined and evaporated. The residue was crystallized from ether and recrystallized from ethyl acetate/hexane for analysis to yield end product as yellow crystals with mp 200°-203° C.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 16 hours
  3. customThe crude product obtained after the usual workup
  4. customwas chromatographed over 60 g of silica gel using 5% (v/v) of ethanol in methylene chloride for elution
  5. customevaporated
  6. customThe residue was crystallized from ether
  7. customrecrystallized from ethyl acetate/hexane for analysis
  8. customto yield end product as yellow crystals with mp 200°-203° C.

Sources & evidence

ORD record
ord-898b0cf24f33414c99eb444100d1f762
Source dataset
uspto-grants-1981_01
Patent number
US04244868

Reaction notes

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