Claims
- 1. A process for preparing the compounds of formula (I) ##STR11## wherein R.sup.1 is lower alkyl containing 1 to 4 carbon atoms, R.sup.2 and R.sup.3 are hydrogen or R.sup.2 and R.sup.3 are joined together to give
- --CH.dbd.CH--CH.dbd.CH--
- and form a benzene ring, R.sup.4 and R.sup.5 are hydrogen, alkyl containing 1 to 6 carbon atoms, halogen, and the pharmaceutically acceptable salts thereof which comprises the steps
- (1) condensing a substituted isatin of formula (III) ##STR12## wherein R.sup.4 and R.sup.5 are as defined above with the enolate of the carboxylic acid ester of formula (IV) ##STR13## wherein R.sup.2 and R.sup.3 are as defined above to produce the intermediate compound of formula (V) ##STR14## wherein R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined above (2) reducing said compound of formula (V) to produce the tryptophol of formula (VI) ##STR15## wherein R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined above (3) reacting the compound of formula (VI) with 3-methoxy-2-alkenoic acid, methyl ester of formula (VII) ##STR16## wherein R.sup.1 is as defined above to produce the methyl ester of compound (I) ##STR17## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined above and hydrolyzing said ester to obtain the compound of formula (I) and, if desired, reacting said compound of formula (I) with a pharmaceutically acceptable inorganic or organic base to produce a pharmaceutically acceptable salt.
- 2. A process for preparing the compounds of formula (I) ##STR18## wherein R.sup.1 is lower alkyl containing 1 to 4 carbon atoms, R.sup.2 and R.sup.3 are hydrogen or R.sup.2 and R.sup.3 are joined together to give
- --CH.dbd.CH--CH.dbd.CH--
- and form a benzene ring, R.sup.4 and R.sup.5 are hydrogen, alkyl containing 1 to 6 carbon atoms, halogen, and the pharmaceutically acceptable salts thereof which comprises the steps
- (1) condensing a substituted indole-3-acetic acid, methyl ester of formula (VIII) ##STR19## wherein R.sup.4 and R.sup.5 are as defined above with the halide of formula (IX) ##STR20## wherein R.sup.2 and R.sup.3 are as defined above and X is halogen selected from the group consisting of chlorine, bromine and iodine to produce the .alpha.-substituted indole-3-acetic acid ester of formula (X) ##STR21## wherein R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined above (2) reducing said compound of formula (X) to produce the compound of formula (VI) ##STR22## wherein R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined above (3) reacting the compound of formula (VI) with 3-methoxy-2-alkenoic acid, methyl ester of formula (VII) ##STR23## wherein R.sup.1 is as defined above to produce the methyl ester of compound (I) ##STR24## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined above and hydrolyzing said ester to obtain the compound of formula (I), and, if desired, reacting said compound of formula (I) with a pharmaceutically acceptable inorganic or organic base to produce a pharmaceutically acceptable salt.
- 3. A process for preparing the compounds of formula (XIV) ##STR25## wherein R.sup.1 is lower alkyl containing 1 to 4 carbon atoms, R.sup.4 and R.sup.5 are hydrogen, alkyl containing 1 to 6 carbon atoms or halogen, and Y is 4-halogen, 2- and 4-dihalogen, 3-trifluoromethyl or 4-methoxy and the pharmaceutically acceptable salts thereof which comprises the steps
- (1) condensing a substituted indole-3-acetic acid, methyl ester of formula (VIII) ##STR26## wherein R.sup.4 and R.sup.5 are as defined above with the halide of formula (XV) ##STR27## wherein Y is as defined above and X is halogen selected from the group consisting of chlorine, bromine and iodine to produce the .alpha.-substituted indole-3-acetic acid ester of formula (XVI) ##STR28## wherein R.sup.4, R.sup.5 and Y are as defined above (2) reducing said compound of formula (XVI) to produce the compound of formula (XVII) ##STR29## wherein R.sup.4, R.sup.5 and Y are as defined above and (3) reacting the compound of formula (XVII) with 3-methoxy-2-alkenoic acid, methyl ester of formula (VII) ##STR30## wherein R.sup.1 is as defined above to produce the methyl ester of compound (XIV) ##STR31## wherein R.sup.1, R.sup.4, R.sup.5 and Y are as defined above and hydrolyzing said ester to obtain the compound of formula (XIV) and, if desired, reacting said compound of formula (XIV) with a pharmaceutically acceptable inorganic or organic base to produce a pharmaceutically acceptable salt.
Parent Case Info
This is a divisional application of copending U.S. Ser. No. 002,825, filed Jan. 13, 1987, now U.S. Pat. No. 4,775,690 which in turn is a continuation-in-part application of both copending U.S. Ser. No. 927,029, filed Nov. 5, 1986, now abandoned, which in turn is a divisional of copending U.S. Ser. No. 838,510, filed Mar. 11, 1986, now U.S. Pat. No. 4,670,462, issued June 2, 1987.
US Referenced Citations (13)
Non-Patent Literature Citations (3)
Entry |
Derwent Abstract of European Patent 5365, published 11/1979. |
Derwent Abstract of Netherlands Patent 7300518, published 7/1973. |
Derwent Abstract of German Patent DE 2301525, published 7/1973. |
Divisions (2)
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Number |
Date |
Country |
Parent |
2825 |
Jan 1987 |
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Parent |
838510 |
Mar 1986 |
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Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
927029 |
Nov 1986 |
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