Dipropylamine → HCID 21308432, compound

HRID 1418903Notes

Reaction equation

HRID 1418903 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][CH:19]=[C:20]([Cl:21])[C:15]=3[C:14](=[O:22])[N:13]3[CH2:23][CH2:24][CH2:25][C@H:12]3[C:11]=12)=[O:6])[C:2]#[CH:3].IN1C(=O)CCC1=O.[CH2:34]([NH:37][CH2:38][CH2:39][CH3:40])[CH2:35][CH3:36]>C(O)(=O)C>[Cl:21][C:20]1[C:15]2[C:14](=[O:22])[N:13]3[CH2:23][CH2:24][CH2:25][C@H:12]3[C:11]3[N:10]([CH:9]=[N:8][C:7]=3[C:5]3[O:6][C:2]([CH2:3][N:37]([CH2:38][CH2:39][CH3:40])[CH2:34][CH2:35][CH3:36])=[CH:1][N:4]=3)[C:16]=2[CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 8902DipropylamineHCID 120273N-IodosuccinimideHCID 86753943HCID 86753943, compound

Product 1

HCID 21308432HCID 21308432, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 1.07 g (0.003 mol) of (S)-8-chloro-9-oxo-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]-benzodiazepine-1-carboxylic acid prop-2-ynylamide in 10 ml of acetic acid was treated with 1.01 g (0.0045 mol) of N-iodosuccinimide. After stirring at room temperature for 12 hrs. the mixture was heated to 50° for a further 4 hrs. The dark suspension obtained was completely freed from solvent in a vacuum and dried azeotropically several times with toluene. The brown residue was dissolved in 10 ml of THF, treated at room temperature with 10 ml (0.073 mol) of dipropylamine and stirred at 50° for 2 hrs. The suspension obtained was completely freed from the solvents and the residue was partitioned between ethyl acetate and 1N aqueous hydrochloric acid and extracted. The acidic phase was made basic and extracted with ethyl acetate. The organic phase was concentrated, the pale brown product was chromatographed over silica gel with dichloromethane/methanol 95:5 as the eluent and digested with diethyl ether. There was obtained 0.65 g (48%) of (S)-8-chloro-1-(5-dipropylaminomethyl-oxazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]-benzodiazepin-9-one; [α]D20 =+11.5° (MeOH, c=1%)

Workup

  1. temperaturethe mixture was heated to 50° for a further 4 hrs
  2. customThe dark suspension obtained
  3. dry with materialdried azeotropically several times with toluene
  4. dissolutionThe brown residue was dissolved in 10 ml of THF
  5. stirringstirred at 50° for 2 hrs
  6. customThe suspension obtained
  7. customthe residue was partitioned between ethyl acetate and 1N aqueous hydrochloric acid
  8. extractionextracted
  9. extractionextracted with ethyl acetate
  10. concentrationThe organic phase was concentrated
  11. customthe pale brown product was chromatographed over silica gel with dichloromethane/methanol 95:5 as the eluent and digested with diethyl ether

Sources & evidence

ORD record
ord-efcc7c7ca0964217b9b68b368d0d5cf6
Source dataset
uspto-grants-1999_03
Patent number
US05885986

Reaction notes

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