Ammonia → 5-(2-chlorophenyl)-1,3-dihydro-7-iodo-2H-1,4-benzodiazepin-2-one

HRID 1032748Notes

Reaction equation

HRID 1032748 reaction equation
[NH3:1].C(=O)=O.Br[CH2:6][C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=1[C:17](=O)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[Cl:24])=[O:8]>C(Cl)Cl>[Cl:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:17]1[C:11]2[CH:12]=[C:13]([I:16])[CH:14]=[CH:15][C:10]=2[NH:9][C:7](=[O:8])[CH2:6][N:1]=1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 280Carbon DioxideHCID 148519552-bromo-N-[2-(2-chlorobenzoyl)-4-iodophenyl]acetamide

Product 1

HCID 136203855-(2-chlorophenyl)-1,3-dihydro-7-iodo-2H-1,4-benzodiazepin-2-oneYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Bromoacetyl bromide, 15 ml, was added to a solution of 52 g (0.145 mol) of (2-amino-5-iodophenyl)(2-chlorophenyl) methanone in 300 ml of methylene chloride cooled to 0° C. A 10% aqueous solution of sodium carbonate, 150 ml, was added slowly with stirring and the two phase system was stirred in the cold for 30 minutes. The organic layer was separated, washed with water and dried over sodium sulfate. The solution was filtered and evaporated. Crystallization of the residue from methylene chloride/ether yielded 61 g (90%) of 2-bromo-N-[2-(2-chlorobenzoyl)-4-iodophenyl]acetamide with m.p. 150°-152° C. A solution of 50 g of this material in 1 liter of methylene chloride was added to 800 ml of liquid ammonia with dry-ice cooling. After refluxing for 16 hours, the cooling was discontinued and the ammonia was allowed to evaporate. The remaining solution was washed with water, dried over sodium sulfate and evaporated under reduced pressure. The residue was dissolved in 1 liter of ethanol and the solution was heated to reflux for 30 minutes after the addition of 15 ml of acetic acid. The crystals separated from the cooled reaction mixture were collected to leave 38 g (89%) of 5-(2-chlorophenyl)-1,3-dihydro-7-iodo-2H-1,4-benzodiazepin-2-one which melted at 260°-262° C. after recrysyallization from tetrahydrofuran/ethanol.

Workup

  1. temperatureAfter refluxing for 16 hours
  2. customto evaporate
  3. washThe remaining solution was washed with water
  4. dry with materialdried over sodium sulfate
  5. customevaporated under reduced pressure
  6. dissolutionThe residue was dissolved in 1 liter of ethanol
  7. temperaturethe solution was heated
  8. temperatureto reflux for 30 minutes
  9. additionafter the addition of 15 ml of acetic acid
  10. customThe crystals separated from the cooled reaction mixture
  11. customwere collected

Sources & evidence

ORD record
ord-90a7a7d12dd9441792eeea0a3a79d240
Source dataset
uspto-grants-1990_09
Patent number
US04959361

Reaction notes

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