Phosgene → 8-Chloro-6-(2-chlorophenyl)-1,2-dihydro-1-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid methyl ester

HRID 26047

Reaction equation

HRID 26047 reaction equation
N[CH2:2][O:3][C:4]([CH:6]=[C:7]1[CH2:13][N:12]=[C:11]([C:14]2C=[CH:18][CH:17]=[CH:16][C:15]=2Cl)[C:10]2[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:9]=2[NH:8]1)=[O:5].O1C(C[O:30][C:31]2C=CC=CC=2)C1.[C:37]([Cl:40])(Cl)=O.[OH-].[NH4+:42].[K+].[Br-]>C(Cl)Cl.C1C=CC=CC=1>[CH3:2][O:3][C:4]([C:6]1[NH:42][C:31](=[O:30])[N:8]2[C:9]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:10]=3[C:11]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:37]=3[Cl:40])=[N:12][CH2:13][C:7]=12)=[O:5]

Participants

8

Reactant 5

HCID 6371PhosgeneHCID 14923Ammonium HydroxideHCID 31217Phenyl glycidyl etherHCID 253877Potassium BromideHCID 700515042-[(amino)methoxycarbonylmethylene]-7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepine

Product 1

HCID 127034758-Chloro-6-(2-chlorophenyl)-1,2-dihydro-1-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 6344DichloromethaneSolvent

Procedure

A stirred solution of 15 g (0.04 mole) of 2-[(amino)methoxycarbonylmethylene]-7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepine and 12 g (0.08 mole) of 1,2-epoxy-3-phenoxypropane in 150 ml of methylene chloride was cooled in an ice-salt bath and treated with 47 g (0.06 mole) of a 12.5% solution of phosgene in benzene at a moderate rate. Stirring in the cold under a drying tube was continued for 2 hours. A cold solution of 3N ammonium hydroxide (50 ml) was added and stirring was continued for 10 min. The organic phase was separated, dried over sodium sulfate and evaporated under reduced pressure. Stirring the oily residue with anhydrous ether gave off-white crystals. The crystals were filtered, washed with ether and air dried on the funnel to yield the end product. Recrystallization from ethanol methylene chloride gave white needles with mp 273°-276° (dec). Uv λ max 223 mμ (ε=43800) 276 (21100) infl 348 (1100) ir (KBr) 3150 (NH) 1720 (COOMe, CO) nmr (CDCl3) δ 3.80 ppm (s, 3, OCH3) 4.11 (broad d, 1) and 5.58 (broad d, 1) (AB-system, J=12 Hz, C4 -H) 6.95 (d, 1, J=2.5 Hz, C7 -H) 7.3-7.8 (m, 5, aromatic H) 7.96 (d, 1, J=8 Hz, C10 -H) 11.19 (broad s, 1, NH).

Workup

  1. stirringstirring
  2. waitwas continued for 10 min
  3. customThe organic phase was separated
  4. dry with materialdried over sodium sulfate
  5. customevaporated under reduced pressure
  6. stirringStirring the oily residue with anhydrous ether
  7. customgave off-white crystals
  8. filtrationThe crystals were filtered
  9. washwashed with ether and air
  10. customdried on the funnel
  11. customto yield the end product
  12. customRecrystallization from ethanol methylene chloride
  13. customgave white needles with mp 273°-276° (dec)

Sources & evidence

ORD record
ord-67330f99046c476a8877197d20621a66
Source dataset
uspto-grants-1979_04
Patent number
US04147875

Linked notes

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