Methanol → 8-chloro-6-(2-chlorophenyl)-1,2-dihydro-1-oxo-4H-imidazo[1,5-a] [1,4]benzodiazepine-3-carboxylic acid

HRID 614985Notes

Reaction equation

HRID 614985 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12](=[O:19])[NH:13][C:14]([C:15]([O:17]C)=[O:16])=[C:10]3[CH2:9][N:8]=[C:7]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[Cl:26])[C:6]=2[CH:27]=1.CO.[OH-].[K+]>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12](=[O:19])[NH:13][C:14]([C:15]([OH:17])=[O:16])=[C:10]3[CH2:9][N:8]=[C:7]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[Cl:26])[C:6]=2[CH:27]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 127034758-Chloro-6-(2-chlorophenyl)-1,2-dihydro-1-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid methyl ester

Product 1

HCID 203945818-chloro-6-(2-chlorophenyl)-1,2-dihydro-1-oxo-4H-imidazo[1,5-a] [1,4]benzodiazepine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 4.02 g (0.01 mole) of 8-chloro-6-(2-chlorophenyl)-1,2-dihydro-1-oxo-4H-imidazo[1,5-a] [1,4]benzodiazepine-3-carboxylic acid, methyl ester, 150 ml of methanol, 15 ml of water and 2 g (0.035 mole) of potassium hydroxide was heated to reflux for 5 hours under a nitrogen atmosphere. The solution was then concentrated down to 40 ml, acidified by addition of 4 ml of glacial acetic acid and crystallized by diluting with water. The precipitate was collected, dried and recrystallized from tetrahydrofuran/methanol/ethyl acetate to yield 8-chloro-6-(2-chlorophenyl)-1,2-dihydro-1-oxo-4H-imidazo[1,5-a] [1,4]benzodiazepine-3-carboxylic acid which was decarboxylated as follows: A solution of 1 g of this acid in 5 ml of ethylene glycol was heated to reflux for 45 min and then partitioned between methylene chloride and saturated sodium bicarbonate solution. The organic layer was washed with bicarbonate solution and water, dried and evaporated. Crystallization of the residue from ethyl acetate/ether gave end product which was further purified by chromatography over 20 g silica gel using methylene chloride/ethyl acetate 1:3. Crystallization from ethyl acetate/ether yielded the pure colorless product with mp 236°-238°. nmr (CDCl3) δ 4.15 ppm (broad d, 1) and 4.86 (broad d, 1) (AB-system, J= 13 Hz, C4 -H) 6.25 l (d, 1, J=2 Hz, C3 -H) 6.98 (d, 1, J=2.5 Hz, C7 -H) 7.1-7.7 (m, 5, aromatic H) 8.0 (d, 1, J=8 Hz, C10 -H) 10.4 (broad s, 1, NH).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 5 hours under a nitrogen atmosphere
  3. concentrationThe solution was then concentrated down to 40 ml
  4. additionacidified by addition of 4 ml of glacial acetic acid
  5. customcrystallized
  6. additionby diluting with water
  7. customThe precipitate was collected
  8. customdried
  9. customrecrystallized from tetrahydrofuran/methanol/ethyl acetate

Sources & evidence

ORD record
ord-7f5c10a001eb4d84ae03da799c589095
Source dataset
uspto-grants-1979_03
Patent number
US04146722

Reaction notes

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