2-Methyl-3-butyn-2-ol → 7-chloro-4,5-dihydro-3-(3-hydroxy-3-methyl-1-butynyl)-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one

HRID 1606970Notes

Reaction equation

HRID 1606970 reaction equation
Br[C:2]1[N:3]=[CH:4][N:5]2[C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([Cl:16])[C:10]=3[C:9](=[O:17])[N:8]([CH3:18])[CH2:7][C:6]=12.[CH3:19][C:20]([OH:24])([C:22]#[CH:23])[CH3:21]>C(NCC)C.C(Cl)Cl.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:16][C:15]1[C:10]2[C:9](=[O:17])[N:8]([CH3:18])[CH2:7][C:6]3[N:5]([CH:4]=[N:3][C:2]=3[C:23]#[C:22][C:20]([OH:24])([CH3:21])[CH3:19])[C:11]=2[CH:12]=[CH:13][CH:14]=1

Participants

7

Reactant 2

HCID 82582-Methyl-3-butyn-2-olHCID 198515903-bromo-7-chloro-4,5-dihydro-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one

Product 1

HCID 198306547-chloro-4,5-dihydro-3-(3-hydroxy-3-methyl-1-butynyl)-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 6344DichloromethaneSolventHCID 8021DiethylamineSolvent

Procedure

3.26 g (10 mmol) of 3-bromo-7-chloro-4,5-dihydro-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one was heated to boiling under reflux overnight with 1.10 g (12 mmol) of 2-methyl-3-butyn-2-ol, 70 mg of bis-(triphenylphosphine)-palladium(II) dichloride and 10 mg of copper(I) iodide in 20 ml of diethylamine and 15 ml of methylene chloride. The reaction mixture was evaporated and the residue was dissolved in methylene chloride. After chromatography of the solution on silica gel while eluting with ethyl acetate and crystallization from ethyl acetate there was obtained 7-chloro-4,5-dihydro-3-(3-hydroxy-3-methyl-1-butynyl)-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one of melting point 194°-195°.

Workup

  1. customThe reaction mixture was evaporated
  2. dissolutionthe residue was dissolved in methylene chloride
  3. washAfter chromatography of the solution on silica gel while eluting with ethyl acetate and crystallization from ethyl acetate

Sources & evidence

ORD record
ord-0a1f3d88acff4796ba8dafac7984f941
Source dataset
uspto-grants-1989_09
Patent number
US04863920

Reaction notes

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