2-Methyl-3-butyn-2-ol → 8-fluoro-4,5-dihydro-3-(3-hydroxy-3-methyl-1-butynyl)-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one

HRID 1607000Notes

Reaction equation

HRID 1607000 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:12]=[N:13][C:14](I)=[C:10]3[CH2:9][N:8]([CH3:16])[C:7](=[O:17])[C:6]=2[CH:18]=1.[CH3:19][C:20]([OH:24])([C:22]#[CH:23])[CH3:21]>C(NCC)C.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>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:12]=[N:13][C:14]([C:23]#[C:22][C:20]([OH:24])([CH3:21])[CH3:19])=[C:10]3[CH2:9][N:8]([CH3:16])[C:7](=[O:17])[C:6]=2[CH:18]=1

Participants

6

Reactant 2

HCID 82582-Methyl-3-butyn-2-olHCID 198306858-fluoro-4,5-dihydro-3-iodo-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one

Product 1

HCID 198515648-fluoro-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 3

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

Procedure

3.57 g (10 mmol) of 8-fluoro-4,5-dihydro-3-iodo-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one was heated to boiling under reflux for 6.5 hours with 0.925 g (11 mmol) of 2-methyl-3-butyn-2-ol, 70 mg of bis-(triphenylphosphine)-palladium(II) dichloride and 10 mg of copper(I) iodide in 30 ml of diethylamine. The reaction mixture was then evaporated and the residue was chromatographed on silica gel while eluting with ethyl acetate. After recrystallization from ethyl acetate there was obtained 8-fluoro-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 165°-167°.

Workup

  1. customThe reaction mixture was then evaporated
  2. customthe residue was chromatographed on silica gel
  3. washwhile eluting with ethyl acetate
  4. customAfter recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-8bb2ab058f95452f96df5557f2177bd9
Source dataset
uspto-grants-1989_09
Patent number
US04863920

Reaction notes

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