Claims
- 1. A process for preparing a compound having the structure: ##STR188## and the pharmaceutically acceptable salts thereof: wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently selected from the group consisting of hydrogen, and substituted and unsubstituted: alkyl having 1-6 carbon atoms, aralkyl, alkenyl and alkynyl having 2-6 carbon atoms, aryl and aralkyl having 6-10 ring carbon atoms and 1-6 carbon atoms in the alkyl chain, cycloalkyl and cycloalkylalkyl having 3 to 6 ring carbon atoms and 1-6 carbon atoms in the alkyl moiety; wherein the substituents on R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are selected from chloro, bromo, fluoro, hydroxyl, amino, mono-, di- and trialkyl substituted amino (each alkyl having 1-6 carbon atoms) alkoxyl having 1-6 carbon atoms, guanidino, cyano, amidino, and carboxyl; comprising treating a compound of the formula: ##STR189## wherein R is a readily removable protecting group selected from acetyl, bromo-t-butoxycarbonyl, benzyloxycarbonyl, formyl, trifluoroacetyl, trimethylsilyl, t-butyldimethylsilyl with a glyoxalate ester wherein the ester moiety is a pharmaceutically acceptable ester moiety or a readily removable blocking group, R.sup.5, selected from benzyl, p-nitrobenzyl, o-nitrobenzyl, pivaloyloxymethyl, bromo-t-butyl to provide a compound having the structure: ##STR190## followed by halogenating with a reagent selected from SOCl.sub.2, POCl.sub.3, oxalyl chloride to provide a compound having the structure; ##STR191## wherein X is chloro followed by treating with triphenylphosphine in a solvent to yield: ##STR192## followed by deblocking and oxidation to yield: ##STR193## followed by treating with oxalyl chloride to yield: ##STR194## followed by treating with thiophenol to yield: ##STR195## followed by treating with a Grignard reagent R.sup.3 -Mg-halo to obtain ##STR196## and followed by heating at 100.degree.-160.degree. C. in a solvent selected from the group consisting of benzene, toluene, dioxane, xylene, or dimethylformamide to yield ##STR197## followed by deblocking.
- 2. A process for preparing a compound having the structure: ##STR198## and the pharmaceutically acceptable salts thereof: wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently selected from the group consisting of hydrogen, and substituted and unsubstituted: alkyl having 1-6 carbon atoms, aralkyl, alkenyl and alkynyl having 2-6 carbon atoms, aryl and aralkyl having 6-10 ring carbon atoms and 1-6 carbon atoms in the alkyl chain, cycloakyl and cycloalkylalkyl having 3 to 6 ring carbon atoms and 1-6 carbon atoms in the alkyl moiety; wherein the substituents on R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are selected from chloro, bromo, fluoro, hydroxyl, amino, mono- di- and trialkyl substituted amino (each alkyl having 1-6 carbon atoms) alkoxyl having 1-6 carbon atoms, guanidino, cyano, amidino, and carboxyl; comprising treating a compound of the formula: ##STR199## with chlorosulphonyl isocyanate to yield: ##STR200## followed by hydrolysis and reduction to yield: ##STR201## followed by hydrolysis to yield: ##STR202## followed by reaction with 2,2-dimethoxypropane in the presence of a catalyst to yield: ##STR203## followed by alkylation and hydrolysis to obtain ##STR204## followed by establishing O-protecting group R to obtain: ##STR205## wherein R is a readily removable protecting group selected from acetyl, bromo-t-butoxycarbonyl, benzyloxycarbonyl, formyl, trifluoroacetyl, trimethylsilyl, t-butyldimethylsilyl and treating the above O-protected intermediate with a glyoxalate ester wherein the ester moiety is a pharmaceutically acceptable ester moiety or a readily removable blocking group, R.sup.5, selected from benzyl, p-nitrobenzyl, o-nitrobenzyl, pivaloyloxymethyl, bromo-t-butyl to provide a compound having the structure: ##STR206## followed by halogenating with a reagent selected from SOCl.sub.2, POCl.sub.3, oxalyl chloride to provide a compound having the structure: ##STR207## wherein X is chloro followed by treating with triphenylphosphine in a solvent to yield: ##STR208## followed by deblocking and oxidation to yield: ##STR209## followed by treating with oxalyl chloride to yield: ##STR210## followed by treating with thiophenol to yield: ##STR211## followed by treating with a Grignard reagent R.sup.3 -Mg-halo and heating at 100.degree.-160.degree. C. in a solvent selected from the group consisting of benzene, toluene, dioxane, xylene, or dimethylformamide; followed by deblocking.
Parent Case Info
This is a continuation-in-part application of U.S. Ser. No. 208,711 filed Nov. 20, 1980, now abandoned which is a division application of U.S. Ser. No. 954,271 filed Oct. 24, 1978, now U.S. Pat. No. 4,260,627, which parental applications are fully incorporated herein by reference.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
4153714 |
Ponsford |
May 1979 |
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4210661 |
Ponsford et al. |
Jul 1980 |
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Divisions (1)
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Number |
Date |
Country |
Parent |
954271 |
Oct 1978 |
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Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
208711 |
Nov 1980 |
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