Decarboxylation process for preparing 4-(3-aminophenyl)pyridines

4-(3-Aminophenyl)pyridines, useful in the preparation of 1-alkyl-1,4-dihydro-4-oxo-7-pyridinyl-3-quinolinecarboxylic acids, are prepared by heating a 2-amino-4-(4-pyridinyl)benzoic acid at decarboxylation temperatures.

FIELD OF THE INVENTION 
This invention relates to 4-(3-aminophenyl)pyridines and more particularly 
to a process for preparing them. 
BACKGROUND 
As disclosed in Sterling Drug's U.S. Pat. Nos. 3,753,993 (Lesher et al.), 
3,907,808 (Lesher and Carabateas), and 4,118,557 (Lesher) and in copending 
applications Ser. No. 495,977 (Walter I), filed May 19, 1983; Ser. No. 
497,026 (Ramachandran I) and Ser. No. 497,027 (Ramachandran II), both 
filed May 23, 1983; Ser. No. 511,831 (Ramachandran and Ranken), Ser. No. 
511,832 (Ramachandran, Ranken, and Wiegand), and Ser. No. 511,913 (Ranken 
and Ramachandran), all filed July 8, 1963, it is known that antibacterial 
1-alkyl-1,4-dihydro-4-oxo-7-pyridinyl-3-quinolinecarboxylic acids can be 
prepared from 4-(3-aminophenyl)pyridines. 
From Mitscher et al., "Quinoline Antimicrobial Agents. 1. Versatile New 
Synthesis of 1-Alkyl-1,3-dihydro-4-oxo-3-quinolinecarboxylic Acids," 
Journal of Medicinal Chemistry, 1978, Vol. 21, No. 5, pp. 485-489, it is 
also known that antimicrobial agents related to the aforementioned 
bactericides can be prepared from the appropriate isatoic anhydrides. 
Copending applications Ser. No. 511,844 (Ranken and Walter), Ser. No. 
511,854 (Ramachandran III), and Ser. No. 511,887 (Walter II), all filed 
July 8, 1983, and Ser. No. 523,462 (Walter and Ranken), filed Aug. 15, 
1983, show that those bactericides can be prepared by a route similar to 
that employed by Mitscher et al.--a route utilizing a 
2-amino-4-(4-pyridinyl)-benzoic acid as an intermediate. 
Since each of the aforementioned processes for preparing 
1-alkyl-1,4-dihydro-4-oxo-7-pyridinyl-3-quinolinecarboxylic acid 
bactericides is a complicated process involving the preparation of several 
intermediates, it is sometimes desirable to have different stages of the 
processes performed by different manufacturers. Versatility could thus be 
contributed by making it possible to cross over from one process to the 
other, i.e., convert an intermediate useful for preparing the bactericides 
by one technique to an intermediate suitable for preparing the 
bactericides by another technique. It would also be desirable to find an 
alternative technique of preparing 4-(3-aminophenyl)pyridines. 
SUMMARY OF INVENTION 
An object of this invention is to provide a novel process for preparing 
4-(3-aminophenyl)pyridines. 
Another object is to provide a process for preparing 
4-(3-aminophenyl)pyridines from 2-amino-4-(4-pyridinyl)benzoic acids. 
A further object is to provide novel processes for preparing 
1-alkyl-1,4-dihydro-4-oxo-7-pyridinyl-3-quinolinecarboxylic acids from 
2-amino-4-(4-pyridinyl)benzoic acids. 
These and other objects are attained by heating a 
2-amino-4-(4-pyridinyl)benzoic acid at a decarboxylation temperature to 
form a 4-(3-aminophenyl)pyridine and, when desired, converting the 
4-(3-aminophenyl)pyridine to a derivative thereof.

DETAILED DESCRIPTION 
2-Amino-4-(4-pyridinyl)benzoic acid useful in the practice of the invention 
are compounds corresponding to the formula: 
##STR1## 
wherein X is hydrogen or an alkali metal and R.sub.2, R.sub.3, R.sub.4, 
and R.sub.5 are independently selected from hydrogen and innocuous 
substituents, such as substituted (e.g., halogenated) and unsubstituted 
aryl or aryloxyaryl groups, halo, etc.--the preferred acids being 
2-amino-4-(4-pyridinyl)benzoic acid and its alkali metal salts. These 
compounds are preferably prepared by the processes of Ranken and Walter or 
the processes of Ramachandran III, the teachings of both of which are 
incorporated herein by reference. Thus, they may be prepared, e.g., by 
oxidizing a 4-(4-alkyl-3-nitrophenyl)pyridine to a 
2-nitro-4-(4-pyridinyl)benzoic acid and reducing the nitro group to an 
amino group or by treating a 4-(4-alkyl-3-nitrophenyl)pyridine with an 
alcoholic base. 
The decarboxylation is accomplished simply by heating the acid at a 
decarboxylation temperature, e.g., at a temperature in the range of about 
200.degree.-300.degree. C., preferably about 240.degree.-250.degree. C., 
for a time sufficient to effect the decarboxylation. This time can vary 
from a few minutes to a few hours, depending on the particular 
decarboxylation temperature employed. 
The process results in the formation of the 4-(3-aminophenyl)pyridine 
corresponding to the acid used as a starting material, i.e., a compound 
corresponding to the formula: 
##STR2## 
wherein R.sub.2, R.sub.3, R.sub.4, and R.sub.5 have the same definitions 
as given above. 
As indicated above, the 4-(3-aminophenyl)pyridines produced by the 
decarboxylation process can be used in the production of antibacterial 
agents, such as the 
1-alkyl-1,4-dihydro-4-oxo-7-pyridinyl-3-quinolinecarboxylic acids of 
Lesher, Lesher et al., and Lesher and Carabateas. When these bactericides 
or their intermediates are desired, they may be prepared by subjecting the 
4-(3-aminophenyl)pyridines to suitable reactions which may be conducted by 
known techniques. For example: 
(1) the 4-(3-aminophenyl)pyridine may be reacted with a dialkyl 
ethoxymethylenemalonate to form a dialkyl 
3-(4-pyridyl)anilinomethylenemalonate, which may be cyclized to an alkyl 
1,4-dihydro-4-oxo-7-(4-pyridyl)-3-quinolinecarboxylate, which in turn may 
be N-alkylated to an alkyl 
1-alkyl-1,4-dihydro-4-oxo-7-(4-pyridyl)-3-quinolinecarboxylate, which may 
then be hydrolyzed to a 
1-alkyl-1,4-dihydro-4-oxo-7-(4-pyridyl)-3-quinolinecarboxylic acid, as in 
Lesher et al. and Lesher and Carabateas, 
(2) the 4-(3-aminophenyl)pyridine may be reductively alkylated, or it may 
be acylated and then reduced, as in Lesher, to form a 
4-(3-alkylaminophenyl)pyridine, otherwise designated as a 
3-(4-pyridyl)-N-alkylaniline, which may then be (a) subjected to the 
reaction steps of Lesher et al. and Lesher and Carabateas without the need 
for their N-alkylation step or (b) subjected to reaction with a cyclic 
alkylidenyl alkoxymethylenemalonate, etc., as in Lesher, to form the 
antibacterial agent, or 
(3) either of the above procedures may be terminated at the end of any step 
to receive a desired product for use in any other desired process, etc. 
The following example is given to illustrate the invention and is not 
intended as a limitation thereof. 
EXAMPLE 
A sample of 2-amino-4-(4-pyridinyl)benzoic acid was heated at 
240.degree.-245.degree. C. for four hours. HPLC analysis of the product 
showed 9 area % 2-amino-4-(pyridinyl)benzoic acid, 7 area % unknown, and 
84 area % 4-(3-aminophenyl)pyridine. 
It is obvious that many variations may be made in the products and 
processes set forth above without departing from the spirit and scope of 
the invention.