Dipropylamine → 3-{5-[(Dipropylamino)methyl]-1,3-oxazol-2-yl}-8-fluoro-5-methyl-4,5-dihydro-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one

HRID 1418910Notes

Reaction equation

HRID 1418910 reaction equation
[CH2:1]([NH:4][C:5]([C:7]1[N:8]=[CH:9][N:10]2[C:16]3[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:15]=3[C:14](=[O:22])[N:13]([CH3:23])[CH2:12][C:11]=12)=[O:6])[C:2]#[CH:3].IN1C(=O)CCC1=O.[CH2:32]([NH:35][CH2:36][CH2:37][CH3:38])[CH2:33][CH3:34]>C(O)(=O)C>[CH2:32]([N:35]([CH2:3][C:2]1[O:6][C:5]([C:7]2[N:8]=[CH:9][N:10]3[C:16]4[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:15]=4[C:14](=[O:22])[N:13]([CH3:23])[CH2:12][C:11]=23)=[N:4][CH:1]=1)[CH2:36][CH2:37][CH3:38])[CH2:33][CH3:34]

Participants

5

Reactant 3

HCID 8902DipropylamineHCID 120273N-IodosuccinimideHCID 54122806HCID 54122806, compound

Product 1

HCID 98663173-{5-[(Dipropylamino)methyl]-1,3-oxazol-2-yl}-8-fluoro-5-methyl-4,5-dihydro-6H-imidazo[1,5-a][1,4]benzodiazepin-6-oneYield 24.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 3.12 g (0.010 mol) of 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid prop-2-ynylamide in 200 ml of acetic acid was treated with 3.36 g (0.015 mol) of N-iodosuccinimide while gassing with argon. After stirring at room temperature for 39 hrs. the dark brown suspension obtained was completely freed from the solvents and dried azeotropically several times with toluene. The brown residue was dissolved in 100 ml of THF, treated with 11.9 ml (0.0865 mol) of dipropylamine and stirred at room temperature for 22 hrs. The brown solution obtained was completely freed from the solvents, the residue was partitioned between ethyl acetate and 1N aqueous hydrochloric acid and extracted. The aqueous-acidic phase was made basic and extracted with ethyl acetate. The organic phase was concentrated, the orange-brownish product was chromatographed over basic Alox (grade III) with dichloromethane/ethyl acetate 4:1 as the eluent and recrystallized from hot isopropyl ether. There was obtained 1.0 g (24%) of 3-(5-dipropylaminomethyl-oxazol-2-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one as yellowish crystals; m.p. 123°-125°.

Workup

  1. customthe dark brown suspension obtained
  2. dry with materialdried azeotropically several times with toluene
  3. dissolutionThe brown residue was dissolved in 100 ml of THF
  4. stirringstirred at room temperature for 22 hrs
  5. customThe brown solution obtained
  6. customthe residue was partitioned between ethyl acetate and 1N aqueous hydrochloric acid
  7. extractionextracted
  8. extractionextracted with ethyl acetate
  9. concentrationThe organic phase was concentrated
  10. customthe orange-brownish product was chromatographed over basic Alox (grade III) with dichloromethane/ethyl acetate 4:1 as the eluent
  11. customrecrystallized from hot isopropyl ether

Sources & evidence

ORD record
ord-7ccd537bcd39425492b9fc9efd257d87
Source dataset
uspto-grants-1999_03
Patent number
US05885986

Reaction notes

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