Claims
- 1. A process for preparing a compound of the formula I or a pharmaceutically acceptable salt or prodrug derivative thereof wherein:R1 is selected from the group consisting of C7-C20 alkyl; where;R10 is selected from the group consisting of halo, C1-C10 alkyl, C1-C10 alkoxy, —S—(C1-C10 alkyl) and halo(C1-C10)alkyl, and t is an integer from 0 to 5 both inclusive; R2 is selected from the group consisting of hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), —S—(C1-C2 alkyl), aryl, aryloxy, and HET; R4 is selected from the group consisting of —CO2H, —SO3H, and —P(O)(OH)2 or salt or prodrug derivatives thereof; and R5 is selected from the group consisting of hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, halo(C2-C6)alkyl, bromo, chloro, fluoro, iodo and aryl; which process comprises the steps ofa) halogenating a compound of formula X where R8 is (C1-C6)alkyl, aryl or HET; with SO2Cl2 to form a compound of formula IX b) hydrolyzing and decarboxylating a compound of formula IX to form a compound of formula VIII c) alkylating a compound of formula VII with a compound of formula VIII to form a compound of formula VI d) aminating and dehydrating a compound of formula VI with an amine of the formula R1NH2 in the presence of a solvent that forms an azeotrope with water to form a compound of formula V e) oxidizing a compound of formula V by heating with a base and a sulfinylating reagent of the formula RSOX where R is —(C1-C6)alkyl or aryl and X is —(C1-C6)alkoxy, halo or —OCO2(C1-C6)alkyl to form a compound of formula IV f) alkylating a compound of the formula IV with an alkylating agent of the formula XCH2R4a where X is a leaving group and R4a is —CO2R4b, —SO3R4b, —P(O)(OR4b)2, or —P(O)(OR4b)H, where R4b is an acid protecting group, to form a compound of formula III g) reacting a compound of formula III with oxalyl chloride and ammonia to form a compound of formula II h) optionally hydrolyzing a compound of formula II to form a compound of formula I; and i) optionally salifying a compound of formula I.
- 2. A process for preparing a compound of the formula I or a pharmaceutically acceptable salt or prodrug derivative thereof wherein:R1 is selected from the group consisting of C7-C20 alkyl; whereR10 is selected from the group consisting of halo, C1-C10 alkyl, C1-C10 alkoxy, —S—(C1-C10 alkyl) and halo(C1-C10)alkyl, and t is an integer from 0 to 5 both inclusive; R2 is selected from the group consisting of hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), —S—(C1-C2 alkyl), aryl, aryloxy, and HET; R4 is selected from the group consisting of —CO2H, —SO3H, and —P(O)(OH)2 or salt or prodrug derivatives thereof; and R5 is selected from the group consisting of hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, halo(C2-C6)alkyl, bromo, chloro, fluoro, iodo and aryl; which process comprises the steps ofe) oxidizing a compound of formula V by heating with a base and a compound of the formula RSOX where R is —(C1-C6)alkyl or aryl and X is —(C1-C6)alkoxy, halo or —OCO2(C1-C6)alkyl to form a compound of formula IV f) alkylating a compound of the formula IV with an alkylating agent of the formula XCH2R4a where X is a leaving group and R4a is —CO2R4b, —SO3R4b, —P(O)(OR4b)2, or —P(O)(OR4b)H, where R4b is an acid protecting group, to form a compound of formula III g) reacting a compound of formula III with oxalyl chloride and ammonia to form a compound of formula II h) optionally hydrolyzing a compound of formula II to form a compound of formula I; and i) optionally salifying a compound of formula I.
- 3. The process of claim 1 or 2 where the sulfinating reagent is p-tolulylsulfinicisobutyric anhydride.
- 4. The process of any one of claims 1 to 3 which prepares ((3-(2-amino-1,2-dioxyethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl)oxy) acetic acid.
Parent Case Info
This application is a 371 of PCT/US99/08332 filed Apr. 15, 1999, which claims benefit of U.S. Provisional Application No. 60/082,110 filed Apr. 17, 1998.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US99/08332 |
|
WO |
00 |
9/27/2000 |
9/27/2000 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO99/54300 |
10/28/1999 |
WO |
A |
Foreign Referenced Citations (2)
Number |
Date |
Country |
0 675 110 |
Apr 1995 |
EP |
0 675 110 A1 |
Apr 1995 |
EP |
Non-Patent Literature Citations (1)
Entry |
Draheim, et al., Journal of Medicinal Chemistry, Indole Inhibitors of Human Nonpancreatic Secretory Phospholipase A2. 3. Indole-3-Glyoxamides, vol. 39, No. 26, p. 5161, Scheme 2 (1996). |
Provisional Applications (1)
|
Number |
Date |
Country |
|
60/082110 |
Apr 1998 |
US |