Substituted indolealkanoic acids

1. A process for preparing a compound of formula I:

or a pharmaceutically acceptable salt thereof wherein

R a is hydrogen, C 1 -C 6 alkyl, fluoro, or trifluoromethyl;

R 1 is hydrogen, alkyl having 1-6 carbon atoms, halogen, 2-, 3-, or 4- pyridyl, or phenyl, where the phenyl or pyridyl is optionally substituted with up to three groups selected from halogen, hydroxy, C 1 -C 6 alkoxy, C 1 -C 6 alkyl, nitro, amino, or mono- or di(C 1 -C 6 )alkylamino;

R 2 , R 3 , R 4 and R 5 are each independently

hydrogen, halogen, nitro, or an alkyl group of 1-6 carbon atoms unsubstituted or substituted with one or more halogens;

OR 7 , SR 7 , S(O)R 7 , S(O) 2 N(R 7 ) 2 , C(O)N(R 7 ) 2 , or N(R 7 ) 2 , wherein each R 7 is independently hydrogen, an alkyl group of 1-6 carbon atoms unsubstituted or substituted with one or more halogens, or benzyl, where the phenyl portion is unsubstituted or substituted with up to three groups independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, amino, and mono or di(C 1 -C 6 )alkylamino;

phenyl or heteroaryl, each of which phenyl or heteroaryl is unsubstituted or substituted with up to three groups independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, amino, and mono- or di(C 1 -C 6 )alkylamino;

phenoxy where the phenyl portion is unsubstituted or substituted with up to three groups independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, amino, and mono or di(C 1 -C 6 )alkylamino; or

a group of the formula

 where

J is a bond, CH 2 , oxygen, or nitrogen; and

each r is independently 2 or 3;

R 6 is hydroxy, benzyloxy, di(C 1 -C 6 )alkylaminoethyloxy, acetoxymethyloxy, pivaloyloxymethyloxy, phthalidoyloxy, ethoxycarbonyloxyethyloxy, 5-methyl-2-oxo-1,3-dioxol-4-yl methyloxy, C 1 -C 6 alkoxy unsubstituted or substituted by N-morpholino, or di(C 1 -C 6 )alkylamino;

and Ar represents benzothiazolyl, where the benzo portion is unsubstituted or substituted by one of iodo, cyano, nitro, perfluoroethyl, trifluoroacetyl, or (C 1 -C 6 )alkanoyl, one or two of fluoro, chloro, bromo, hydroxy, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylthio, trifluoromethoxy, trifluoromethylthio, (C 1 -C 6 )alkylsulfinyl, (C 1 -C 6 )alkylsulfonyl or trifluoromethyl, or two fluoro or two trifluoromethyl with one hydroxy or one (C 1 -C 6 )alkoxy, or one or two fluoro and one trifluoromethyl, or three fluoro;

comprising

(a) heating a solution containing (i) a protected acid of formula V

 where

R a , R 1 , R 2 , R 3 , R 4 , and R 5 are as defined above; and

Ar 2 is unsubstituted phenyl or phenyl substituted by one of iodo, cyano, nitro, perfluoroethyl, trifluoroacetyl, or (C 1 -C 6 )alkanoyl, one or two of fluoro, chloro, bromo, hydroxy, (C 1 -C 6 ) alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylthio, trifluoromethoxy, trifluoromethylthio, (C 1 -C 6 )alkylsulfinyl, (C 1 -C 6 )alkylsulfonyl or trifluoromethyl, or two fluoro or two trifluoromethyl with one hydroxy or one (C 1 -C 6 )alkoxy, or one or two fluoro and one trifluoromethyl, or three fluoro;

R 61 is benzyloxy, di(C 1 -C 6 )alkylaminoethyloxy, acetoxymethyloxy, pivaloyloxymethyloxy, phthalidoyloxy, ethoxycarbonyloxyethyloxy, 5-methyl-2oxo-1,3-dioxol-4-yl methyloxy, C 1 -C 6 alkoxy unsubstituted or substituted by N-morpholino, or di(C 1 -C 6 )alkylamino;

and (ii) potassium ferricyanide or sodium hydride;

to produce a protected acid of Formula VII

 and

(b) optionally removing the protecting group from the protected acid VII.

2. The process of claim 1 , wherein the protected acid is prepared according to the process comprising,

contacting a compound of the formula,

with P 2 S 5 .

3. The process of claim 2 , wherein the compound of the formula,

is prepared according to the process comprising,

contacting a compound of the formula,

with a compound of the formula, HNAr 2 , in the presence of a amide coupling reagent.

4. The process of claim 3 , wherein the amide coupling reagent is 1,3-dicyclohexylcarbodiimide.

5. The process of claim 2 , wherein the compound of the formula,

is prepared according to the process comprising,

contacting a compound of the formula,

with an acid chloride forming reagent to produce an acid chloride intermediate; and

contacting the acid chloride intermediate with a compound of the formula, HNAr 2 .

6. The process of claim 2 , wherein the compound of the formula

is prepared according to the process comprising,

contacting a compound of the formula,

with an mixed anhydride forming reagent to produce a mixed anhydride intermediate; and

contacting the mixed anhydride intermediate with a compound of the formula, HNAr 2 .