Water → HCID 15943230, compound

HRID 342311Notes

Reaction equation

HRID 342311 reaction equation
BrBr.O=C1C2C=CC=CC=2N(C([C:17]2[CH:35]=[CH:34][C:20]([NH:21][C:22](=[O:33])[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[O:29][CH:30]([CH3:32])[CH3:31])=[CH:19][CH:18]=2)=O)CCC1.O>C(Cl)(Cl)Cl>[CH:30]([O:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[C:22]([NH:21][C:20]1[CH:19]=[CH:18][CH:17]=[CH:35][CH:34]=1)=[O:33])([CH3:32])[CH3:31]

Participants

5

Reactant 3

HCID 962WaterHCID 24408Bromine2×HCID 10694496HCID 10694496, compound

Product 1

HCID 15943230HCID 15943230, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A 1.32 g portion of bromine dissolved in 6.6 ml of chloroform was dropwise added gradually (spending about 60 minutes) to 36 ml of chloroform solution containing 3.55 g of 4'-[(5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]-2-isopropoxybenzanilide at room temperature. When disappearance of the color of bromine was confirmed, the reaction solution was washed with a saturated sodium bicarbonate aqueous solution. The resulting organic layer was dried over anhydrous magnesium sulfate, concentrated under a reduced pressure and then evaporated to dryness using a vacuum pump. The thus obtained solid substance was dissolved in 40 ml of chloroform, and the resulting solution was mixed with 5.0 g of cyclopropylcarbamidine hydrochloride and 8.02 g of potassium carbonate and subjected to 20 hours of heating under reflux in a stream of argon. The resulting reaction solution was mixed with water to effect phase separation, and the separated organic layer was dried over anhydrous magnesium sulfate. After removing the solvent by distillation under a reduced pressure, the thus obtained residue was crystallized from toluene to obtain 2.96 g of 4'-[(2-cyclopropyl-1,4,5,6-tetrahydroimidazol4,5-d][1]benzazepin-6-yl)carbonyl]-2-isopropoxybenzanilide. A 1.08 g portion of this compound was dissolved in 20 ml of ethyl alcohol, mixed with 0.8 ml of 4N hydrochloric acid-ethyl acetate and recrystallized to obtain 916 mg of 4'-[(2-cyclopropyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)carbonyl]-2-isopropoxybenzanilide hydrochloride.

Workup

  1. washthe reaction solution was washed with a saturated sodium bicarbonate aqueous solution
  2. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under a reduced pressure
  4. customevaporated to dryness
  5. dissolutionThe thus obtained solid substance was dissolved in 40 ml of chloroform
  6. additionthe resulting solution was mixed with 5.0 g of cyclopropylcarbamidine hydrochloride and 8.02 g of potassium carbonate
  7. temperatureof heating
  8. temperatureunder reflux in a stream of argon
  9. customThe resulting reaction solution
  10. customphase separation
  11. dry with materialthe separated organic layer was dried over anhydrous magnesium sulfate
  12. customAfter removing the solvent
  13. distillationby distillation under a reduced pressure
  14. customthe thus obtained residue was crystallized from toluene

Sources & evidence

ORD record
ord-1e0ad444adf6455eb9fe07dfadb7fa29
Source dataset
uspto-grants-1999_01
Patent number
US05856564

Reaction notes

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