Propylamine → HCID 21842244, compound

HRID 1418908Notes

Reaction equation

HRID 1418908 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].I[N:25]1C(=O)[CH2:28][CH2:27][C:26]1=O.C(N)CC>C(O)(=O)C>[F:21][C:19]1[CH:18]=[CH:17][C:16]2[N:10]3[CH:9]=[N:8][C:7]([C:5]4[O:6][C:2]([CH2:3][NH:25][CH2:26][CH2:27][CH3:28])=[CH:1][N:4]=4)=[C:11]3[CH2:12][N:13]([CH3:23])[C:14](=[O:22])[C:15]=2[CH:20]=1

Participants

5

Reactant 3

HCID 7852PropylamineHCID 120273N-IodosuccinimideHCID 54122806HCID 54122806, compound

Product 1

HCID 21842244HCID 21842244, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 10 g (0.032 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 10.8 g (0.048 mol) of N-iodosuccinimide while gassing with argon. After stirring at room temperature for 90 hrs. the dark suspension obtained was completely freed from the solvents and dried azeotropically several times with toluene. The dark residue was dissolved in 200 ml of THF, treated with 23 ml (0.278 mol) of propylamine and stirred at room temperature for 5 hrs. The suspension 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 and the orange crystalline product was chromatographed twice; firstly over basic Alox (grade III) with ethyl acetate/methanol 4:1 as the eluent, then over silica gel with dichloromethane/methanol 9:1 as the eluent. There were obtained 1.17 g (10%) of 8-fluoro-5-methyl-3-(5-propylaminomethyl-oxazol-2-yl)-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one as yellowish crystals; m.p. 134°-136°.

Workup

  1. customthe dark suspension obtained
  2. dry with materialdried azeotropically several times with toluene
  3. dissolutionThe dark residue was dissolved in 200 ml of THF
  4. stirringstirred at room temperature for 5 hrs
  5. customThe suspension 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 crystalline product was chromatographed twice

Sources & evidence

ORD record
ord-6950e0c956bc4c7aad604ac2eb20b662
Source dataset
uspto-grants-1999_03
Patent number
US05885986

Reaction notes

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