Cyclopropylacetylene → 7-chloro-3-(cyclopropylethynyl)-4,5-dihydro-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one

HRID 1606990Notes

Reaction equation

HRID 1606990 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:18])[N:9]([CH3:17])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3I)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH:19]1([C:22]#[CH:23])[CH2:21][CH2:20]1>C(NCC)C.C(Cl)CCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:1][C:2]1[C:7]2[C:8](=[O:18])[N:9]([CH3:17])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:23]#[C:22][CH:19]3[CH2:21][CH2:20]3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 2

HCID 138823CyclopropylacetyleneHCID 198306597-chloro-4,5-dihydro-3-iodo-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one

Product 1

HCID 198515147-chloro-3-(cyclopropylethynyl)-4,5-dihydro-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 111,2-DichloroethaneSolventHCID 8021DiethylamineSolvent

Procedure

3.37 g (10 mmol) of 7-chloro-4,5-dihydro-3-iodo-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one was heated to 75° for 16 hours with 1.47 g of cyclopropylacetylene, 70 mg of bis-(triphenylphosphine)-palladium(II) dichloride and 20 mg of copper(I) iodide in 20 ml of diethylamine and 10 ml of ethylene chloride. By evaporation of the reaction mixture and chromatography of the residue on silica gel while eluting with ethyl acetate there was obtained a mixture of product and starting material. In order to remove the starting material, the mixture was heated under reflux for 4 hours with 1 ml of 2-methyl-3-butyn-2-ol, 70 mg of bis-(triphenylphosphine)-palladium(II) dichloride and 20 mg of copper(I) iodide in 10 ml of diethylamine and 10 ml of ethylene chloride. By evaporation of the reaction mixture and chromatography of the residue on silica gel while eluting with ethyl acetate the byproduct can be separated from the desired product. After crystallization from ethyl acetate there was obtained 7-chloro-3-(cyclopropylethynyl)-4,5-dihydro-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one of melting point 177°-178°.

Workup

  1. customBy evaporation of the reaction mixture and chromatography of the residue on silica gel
  2. washwhile eluting with ethyl acetate
  3. customthere was obtained
  4. additiona mixture of product
  5. customIn order to remove the starting material
  6. temperaturethe mixture was heated
  7. temperatureunder reflux for 4 hours with 1 ml of 2-methyl-3-butyn-2-ol, 70 mg of bis-(triphenylphosphine)-palladium(II) dichloride and 20 mg of copper(I) iodide in 10 ml of diethylamine and 10 ml of ethylene chloride
  8. customBy evaporation of the reaction mixture and chromatography of the residue on silica gel
  9. washwhile eluting with ethyl acetate the byproduct
  10. customcan be separated from the desired product
  11. customAfter crystallization from ethyl acetate

Sources & evidence

ORD record
ord-3c95c1d79ed44b299f1136040214473c
Source dataset
uspto-grants-1989_09
Patent number
US04863920

Reaction notes

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