Preparation of N1-(2′-pyridyl)-1,2-propanediamine...

Details Preparation of N1-(2′-pyridyl)-1,2-propanediamine... Preparation of N1-(2′-pyridyl)-1,2-propanediamine...

2003-03-10

2004-08-31

Desai, Rita (Department: 1625)

Organic compounds -- part of the class 532-570 series

Organic compounds

Nitrogen attached directly or indirectly to the purine ring...

C546S304000, C546S309000, C546S312000

Reexamination Certificate

active

06784294

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to the field of processes for preparing N-aryl piperazines and intermediates therefor.
BACKGROUND OF THE INVENTION
Piperazines of formula A
wherein R is a lower alkyl, Ar is an unsubstituted or substituted aryl or heteroaryl, and Q is a hydrogen, CO-(lower) alkyl, CO-cycloaklyl, or CO-aryl, and * indicates a chiral center are potent 5HT
1A
receptor binding agents. U.S. Pat. No. 6,127,357 teaches piperazine derivatives that are useful in the treatment of Central Nervous System (CNS) disorders. Enantiomers of such piperazines can display differnet binding abilities to 5HT
1A
receptors. Therefore, their potency, selectivity, and metabolic effects may be different. WO 9703982 teaches that certain enantiomers of such piperazines display improved 5HT
1A
binding affinity and bioavailability. Therefore, an efficient, operationally facile, inexpensive and safe alternative process for making the optically preferred piperazines is desirable.
WO 9533725 teaches a method for synthesizing some chiral piperazines of formula A by alkylation of the corresponding 1-aryl-piperazine with enantiomerically pure 2-(5-methyl-2,2-dioxido-1,2,3-oxathiazolidin-3-yl)pyridine. WO 9533725 also teaches nucleophilic ring openings of sulfamidates with 1-aryl-piperazine and opening with various primary and secondary amines is known form L. T. Boulton,
J. Chem. Soc., Perkin Trans.
1, 1999, 1421-1429.
WO 97/37655 and Cignarella et al., Farmaco Ed. Sci.; 31; 1976; 194, 196 discuss preparation and reaction of N1-(2′pyridyl)-1,2-propane-diamine.
SUMMARY OF THE INVENTION
The present invention is a process for making an N1-(2′-pyridyl)-1,2-alkanediamine sulfamic acid of formula II comprising reacting a compound of formula I with NH
2
R′
wherein R is selected form the group consisting of C
1
-C
3
alkyl, and R′ is H, C
1
-C
6
alkyl, C
3
-C
7
cycloalkyl, C
2
-C
7
acyl, C
5
-C
10
aryl C
6
-C
11
aroyl, (C
3
-C
7
)cycloalkyl(C
1
-C
6
)alkyl, di-(C
3
-C
7
)cycloalkyl-(C
1
-C
6
)alkyl, (C
5
-C
10
)aryl(C
1
-C
6
)alkyl, and di-(C
5
-C
10
)aryl-(C
1
-C
6
)alkyl. The invention further comprises the compound of formula II and optical isomers thereof.
The invention also includes processes that comprise one or more of the following reaction steps:
The compound of formula II may be hydrogenated to convert R′ to H, if it is not already H, and then hydrolyzed using an acid to form the compound of formula III
Either the compound of formula II where R′═H, or the compound of formula III, may be reacted with the compound of formula IV to form the compound of formula V
wherein Ar is a dihydrobenzodioxinyl or benzodioxinyl, or phenyl optionally substituted with up to three substituents independently selected from halogen, methoxy, halomethyl, dihalomethyl and trihalomethyl, and L is a suitable group such as halo (especially chloro or bromo), tosylate, mesylate or p-bromophenyl-sulfonyloxy.
The compound of formula V may be treated an with aroyl compound selected from aroyl chloride, aroyl bromide and aroyl anhydride, in the presence of a base, to form a compound of formula VI
wherein Aryl represents a C
6
-C
12
aromatic group optionally substituted with up to three substituents independently selected from the group consisting of halogen atoms, alkyl, alkoxy, alkoxycarbonyl, nitro, amino, alkylamino, dialkylamino, haloalkyl, dihaloalkyl, trihaloalkyl, nitrile and amido substituents each having no more than six carbon atoms.
It is an object of the present invention to provide a novel intermediate compound of formula II useful in preparing N-aryl piperazines.
It is a further object of this invention to provide a novel process for making N-aryl piperazines and intermediates therefor.
It is another object of the invention to provide a novel process for making a compound of formula II.
Other objects and advantages of the present invention will be apparent to those skilled in the art from consideration of the detailed description of the invention provided herein, and from the appended claims.


REFERENCES:
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patent: 6127357 (2000-10-01), Cliffe et al.
patent: 01125357 (1989-05-01), None
patent: WO 94/24115 (1994-10-01), None
patent: WO 95/33725 (1995-12-01), None
patent: WO 95/33743 (1995-12-01), None
patent: WO 97/03982 (1997-02-01), None
patent: WO 97/37655 (1997-10-01), None
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