Butyryl chloride → HCID 13343344, compound

HRID 1263056Notes

Reaction equation

HRID 1263056 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][NH2:13])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[C:6]=2[CH:20]=1.[C:21](Cl)(=O)[CH2:22][CH2:23][CH3:24].C(=O)(O)[O-].[Na+]>O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:21]([CH2:22][CH2:23][CH3:24])=[N:13][N:12]=[C:10]3[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[C:6]=2[CH:20]=1

Participants

5

Reactant 3

HCID 8855Butyryl chloride2×HCID 516892Sodium BicarbonateHCID 12612400HCID 12612400, compound

Product 1

HCID 13343344HCID 13343344, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1.5 g of 7-bromo-2-hydrazino-5-(2-pyridinyl)-3H-1,4-benzodiazepine in 45 ml of tetrahydrofuran cooled in an ice bath over a nitrogen atmosphere is added 0.57 ml of butyryl chloride dropwise over 90 sec. After stirring for 4.5 hrs, there is added an additional 0.1 ml of butyryl chloride. The resulting mixture is then stirred at ambient temperature for 18 hrs, poured into 300 ml of aqueous sodium bicarbonate and filtered. The filtrate is extracted with dichloromethane, washed with dilute brine, dried over sodium sulphate, and concentrated under reduced pressure. The resulting residue is then heated in an oil bath at 120°-125° C. for 45 min, allowed to cool, and concentrated under reduced pressure. The residue is then dissolved in dichloromethane, washed with aqueous sodium bicarbonate and dilute brine, dried over sodium sulphate, and concentrated under reduced pressure. The resulting residue is then chromatographed on 150 g of silica gel eluting with 2.5% methanol in dichloromethane. Crystallization from ethyl acetate yields 0.27 g of title product. Melting point is 184°-186° C.

Workup

  1. temperaturecooled in an ice bath over a nitrogen atmosphere
  2. stirringThe resulting mixture is then stirred at ambient temperature for 18 hrs
  3. filtrationfiltered
  4. extractionThe filtrate is extracted with dichloromethane
  5. washwashed with dilute brine
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated under reduced pressure
  8. temperatureThe resulting residue is then heated in an oil bath at 120°-125° C. for 45 min
  9. temperatureto cool
  10. concentrationconcentrated under reduced pressure
  11. dissolutionThe residue is then dissolved in dichloromethane
  12. washwashed with aqueous sodium bicarbonate and dilute brine
  13. dry with materialdried over sodium sulphate
  14. concentrationconcentrated under reduced pressure
  15. customThe resulting residue is then chromatographed on 150 g of silica gel eluting with 2.5% methanol in dichloromethane
  16. customCrystallization from ethyl acetate

Sources & evidence

ORD record
ord-15ef43d979944604ba9fe0a2824f6319
Source dataset
uspto-grants-1984_06
Patent number
US04455307

Reaction notes

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