1,4-diazabicylo[3,2,2]nonane derivatives, their...

Details 1,4-diazabicylo[3,2,2]nonane derivatives, their... 1,4-diazabicylo[3,2,2]nonane derivatives, their...

2001-07-16

2002-06-18

Raymond, Richard L. (Department: 1624)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

C540S567000

Reexamination Certificate

active

06407095

ABSTRACT:

The compounds of the present invention correspond to the general formula (I)
in which
one of the symbols X, Y and Z represents a nitrogen atom, another represents a group of formula C—R
3
and the third represents a nitrogen atom or a group of formula C—R
4
,
R
3
and R
4
represent, independently of each other, a hydrogen or halogen atom or a trifluoromethyl, cyano, hydroxyl, (C
1
-C
6
)alkyl or (C
1
-C
6
)alkoxy group.
R
1
and R
2
represent, independently of each other, a hydrogen or halogen atom or a trifluoromethyl, cyano, hydroxyl, (C
1
-C
6
)alkyl or (C
1
-C
6
)alkoxy group or a phenyl group optionally substituted with a halogen atom, with a trifluoromethyl group, with a cyano group, with a nitro group, with a hydroxyl group, with a (C
1
-C
6
)alkyl group, with a (C
1
-C
6
)alkoxy group, with an acetyl group, with a methylenedioxy group, with a trifluoromethoxy group, with a methylthio group or with a phenyl group.
The compounds of the invention can exist in the form of bases or of addition salts with acids.
The preferred compounds are those in the formula of which the heterocycle containing X, Y and Z is a 3-pyridyl or 3-pyridazinyl group.
In accordance with the invention, and according to the scheme which follows, the compounds of general formula (I) can be prepared by reacting 1,4-diazabicyclo[3.2.2]nonane, of formula (II), with a heterocyclic compound of general formula (III), in which X, Y, Z, R
1
and R
2
are as defined above and W represents a halogen atom.
A Buchwald coupling (
J. Org. Chem
. (1997) 62 6066-6068) can thus be carried out in the presence of a palladium catalyst such as palladium acetate, tris(dibenzylideneacetone)dipalladium(0), etc., a complexation ligand such as triphenylphosphine, tributylphosphine or 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, and a base, for example an organic base such as sodium t-butoxide, or an inorganic base such as caesium carbonate.
When X or Z represents a nitrogen atom, a nucleophilic substitution reaction can also be carried out in the presence of a strong base such as caesium carbonate or triethylamine.
1,4-Diazabicyclo[3.2.2]nonane is described in
J. Med. Chem
. (1993) 36 2311-2320.
For certain compounds, the substituents R
1
and/or R
2
are not present in the starting compound of general formula (III); depending on their nature, these substituents can be introduced onto the final compound of general formula (I). Thus, for example, compounds of general formula (I) in which R
1
and/or R
2
represent aryl groups, can be prepared from the corresponding compounds, in the formula of which R
1
and/or R
2
represent bromine or iodine atoms, according to any known method, such as a Suzuki coupling in the presence of a boronic acid and a palladium catalyst, for example tetrakis(triphenylphosphine)palladium.
The compounds of general formula (III) are commercially available or are accessible by methods described in the literature.
The examples which follow illustrate the preparation of a number of compounds of the invention. The elemental microanalyses and the IR and NMR spectra confirm the structures of the compounds obtained.
The numbers given in parentheses in the example titles correspond to those in the first column of Table 1 given later.
In the compound names, the hyphen “—” forms part of the name, and the underscore mark “_” serves merely to indicate the line break; it should be removed if a line break does not occur at that point, and should not be replaced either by a normal hyphen or by a space.


REFERENCES:
patent: 5478939 (1995-12-01), Tryulski et al.
patent: 0400661 (1990-12-01), None
patent: WO 96/30372 (1996-10-01), None
DeCosta et al., J. Med. Chem., 36(16), 1993, pp. 2311-2320

Affiliated with

Also associated with

Rating

1,4-diazabicylo[3,2,2]nonane derivatives, their... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with 1,4-diazabicylo[3,2,2]nonane derivatives, their..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 1,4-diazabicylo[3,2,2]nonane derivatives, their... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2917400