Benzodiazepine → N-methylbenzodiazepine

HRID 1435802Notes

Reaction equation

HRID 1435802 reaction equation
[NH:1]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[CH:5]=[CH:4][CH:3]=[N:2]1.[CH3:12]I.[H-].[Na+]>>[CH3:12][N:1]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[CH:5]=[CH:4][CH:3]=[N:2]1

Participants

3

Reactant 2

HCID 134664BenzodiazepineHCID 23686416Methyl iodide sodium hydride

Product 1

HCID 12543525N-methylbenzodiazepine

Procedure

The bromide 20 (Bogatskii A V, et al., (1977) Pharm Chem J (Engl Transl) 11:1520-1525; Vejdelek Z, Protiva M (1983) Collect Czech Chem Commun 48:1477-1482) was reacted with trimethylsilyacetylene in the presence of a palladium catalyst to provide trimethylsilyl analog 52. This product was methylated with methyl iodide/sodium hydride to give the N-methyl benzodiazepine 54 (XLi 351). This was subjected to fluoride-mediated desilylation to furnish 53 (XLi 350) from 53 and 55 (XLi 352) from 54.

Workup

  1. customVejdelek Z, Protiva M (1983) Collect Czech Chem Commun 48:1477-1482)
  2. customwas reacted with trimethylsilyacetylene in the presence of a palladium catalyst
  3. customto provide trimethylsilyl analog 52

Sources & evidence

ORD record
ord-fff88c841036420e8710bf6cfacda0a0
Source dataset
uspto-grants-2009_11
Patent number
US07618958B2

Reaction notes

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