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Publication numberUS2631164 A
Publication typeGrant
Publication dateMar 10, 1953
Filing dateMay 8, 1952
Priority dateMay 8, 1952
Publication numberUS 2631164 A, US 2631164A, US-A-2631164, US2631164 A, US2631164A
InventorsDavid I Weisblat, Barney J Magerlein
Original AssigneeUpjohn Co
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Keto acetal compounds and their preparation
US 2631164 A
Abstract  available in
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Claims  available in
Description  (OCR text may contain errors)

Patented Mar. 10, .1953

UNITED PATENT OFFICE" KETO ACETAL COMPOUNDS AND THEIR PREPARATION David I. Weisblat, \Galesburg, :and Barney Magerlein, Kalamazoo, Mich., assignors ,to The Upjohn Company, Kalamazoo, Mich.,a eorporation of Michigan No Drawing. Application Mar 18, .1952, Serial "No. 286322 15 Claims. (Cl. 260470) This invention relates to certain keto acetal estersand acidsrand to a method for :their preparation. This application a -.,eontinuation- -in part .of-applicaLtion Serial No. 63,45'3pfiledDecember x3,1948.

Keto cacetal-comp'ounds of the invention, which can be prepared by the :method ;,given herein, sometimes referred to herein has .N-.(3 ,-3-.dialkorgyJ-ketopnopyl) :N- rtarylsulfonyl) peaminobenzoate compounds havestheggeneric formula media given, andinth'ose givensubsequentlynepresents zero :or the -;integer..1, i. e. those c0nte1-nin-g either no giutamic acid or esticrrresidue --,o r only one -glutamic :acid or ester residue, and the method will he described with particular reference thereto.

. "Compounds having 41118 generic fonmula given above :are of particular :evalue ask-intermediates the preparation of compounds similar totorcidentical with certain naturallyoccurr'mg compounds (aim-0 ),on-Q'o-mHHNGcotNnenomcmo 0 non 1 enzoate compound wherein R "is a member o'f.;the group consisting or hydrogen and the :alkyl radicals .and n .is a member dfthegroup consistingoi zero t.and"the pos'itivefintegers "1 to .Z, inclusive. They ,thusinelude N 'substitution products of 'p-aminobenzoic acids, of ,p-aminobenzoyleglutamic acid, of the .p-aminobenzoy1+g1utamylg1utamic acids having up to '7 glutanii'c :acid residues in the ,mc'ilecule,

and of their esters, theiNesubstituentlbeinglin In the structural Iformulae egiven herein :and in the appendedrilaims, aromatic. nucleisare represented by one 'ormore s'impl'e i'hexajgons. In the "naming go'f compounds "having the ,generic formula given and of other compounds mentioned herein wherein both aglutamic acid residue :and a p-aimno'benzoic acid "residue .are included in the moleculejth'e nitrogen atom .of theglutamic acid residue is, for conveniencelherein.referred to :by the 'symbol N "and the nitrogen vatom .of the .p-aminobenzoicacid.residueistreferredLtolby the symbol N. indicatedibythe,genericiormula, compounds used inor preparedlby..the,pro.c-

ess of Tthe linvention which :.contain -more lthan one jglutamic acid .or tester residue vare. .those wherein only the jgamma carboxyl yroupsQ-are involvedin theppeptidellinkages. TBreferredecompounds usedlin ornprenaredlby the methodnf the invention are those Whereinrn 'ofthergeneric 'for-r ofthe'iolicacid roup. 'Ihusas described in'i parent application ..referr.ed to, the Iketo acetall compounds '(IV) of the invention can "be condensed readily with 2,4,5etriaminoefi hydmxw pyrimidine to form alkyl "N-(IZ-amino-eihydroxy-fiepteridyl) emethyl) p-eaminobenzoates 0r dialkyl. :N'-.(N-;( (2eaminoeehydroxy epteridyl) methyl) N- '(arylsulfonyl) paminobenzoyl) glutamates, .91 the .free acids, depending upo the particularlketo uacetal esterpr acid emiiloyed. These l latter ccompounds can, in turmihy'hydrdlysisof the ester groups with 'alkalies in lthegqase m n s .t 'be described are, however, notrlimited asto Ithe econfigurationtof the te'lutamicacid liesidues involved.

N- (arylsulfonyl)-p-aminobenzoate ester 4 subsequent reactions. Gentle alkaline hydrolysis of the N- (3,3-dialkoxy-2-ketopropyl) -N- (arylsulfonyD-p-aminobenzoate compounds which are esters leads to the formation of the corresponding acids. The hydrolysis can be effected by mixing the ester with an aqueous or alcoholic alkali. Upon acidifying the cold aqueous reaction mixture, the acid is precipitated in the form of a solid or oily material which is generally somewhat yellowish in color. The solid compounds can be purified, if desired, by recrystallization from alcohol.

Certain of the N-(arylsulfonyl)-p-aminobenzoate esters (II) are described and claimed in co-pending application Serial-No. 41,888, filed 1 oxidation (Ci-Oz) N-(3,3-dlalkoxy-2-ketopropyl)-N-Karylsullonyl)-p-aminobenzoate compound The process of the invention, as illustrated in the accompanying reaction chart wherein the formulae of the compounds given are numbered to correspond with the following description and wherein n and B have the values given previously, comprises the step of oxidizing an N-(3,3- dialkoxy-2-hydroxypropyl) -N-(arylsulfonyl) paminobenzoate compound (III) to form an N- (3,3-dialkoxy-2-ketopropyl) N (arylsulfonyl) p-aminobenzoate compound (IV). The oxidation can be carried out conveniently using chromic oxide, although any other suitable oxidizing agent can be employed. Either the hydroxy acetal acids or their alkyl esters can be oxidized to the corresponding keto acetal acids or esters. Both the hydroxy acetal esters and the keto acetal esters can be hydrolyzed readily to the corresponding hydroxy acetal acids and keto acetal acids.

The oxidation of an N-(3,3-dialkoxy-2-hydroxypropyl) -N-(arylsulfonyl) -p-aminobenzoate compound to an N-(3,3-dialkoxy-Z-ketopropyl)- N-(arylsulfonic) -p-aminobenzoate compound can becarriedout conveniently by dissolving the hydroxy compound and chromic anhydride in glacial acetic acid and agitating the mixture for several hours, 'e. g. at room temperature. The reaction mixture then generally consists of a mixture of liquid and solid substances from which the keto compound can be recovered in any convenient manner. If desired, the mixture can be agitated thoroughly with ether and filtered or it can be diluted with water andthen extracted with benzene or ethyl acetate. In either case, the organic layer or solution can be washed free of acid and inorganic salts with Water, dried with sodium sulfate or other suitable agent and the solvent then distilled in vacuo to leave the N-(3,3-dialkoxy-Z-ketopropyl) -N-(arylsulf0nyl) -p aminobenzoate compound, generally as a yellowish sirupy residue.

In some instances, the product can be obtained in partially crystalline form upon allowing the oily product to stand. The crude product can, however, be used without further purification in July 31, 1948. They can be prepared readily, as described in the co-pending application just mentioned, by reacting an arylsulfonyl halide with an alkyl ester of p-aminobenzoic acid, of p-aminobenzoyl-glutamic acid, or of a p-aminobenzoyl-glutamyl-glutamic acid having up to 7 glutamic acid residues in the molecule.

Dialkyl acetals of 1,2-oxidopropanol which can be used in the process include the dimethyl, diethyl, di-n-propyl, di-iso-propyl, dibutyl, diamyl and other dialkyl acetals. As a matter of convenience and availability dialkyl acetals wherein the alkyl radicals each contain less than 8 carbon atoms are preferred, although others can be used, if desired. It is apparent that the nature of the alkyl groups in the 3,3-dialkyl-2- hydroxypropyl and in the 3,3-dialkyl-2-ketopropyl radicals of the compounds (III) and (IV) are determined by the particular 1,2-oxidopropanol diallzyl acetal used in the first step of the process.

Esters which can be used as starting com pounds in the process, with the production of the corresponding ester intermediates, include the methyl, ethyl, n-propyl, iso-propyl, butyl, amyl, hexyl, nonyl and other 'alkyl esters. As a matter of convenience, lower alkyl esters containing less than about" 8 carbon atoms in the alkyl radicals are preferably used in the process, although insofar as is knomrany alkyl ester can be used.

Although starting compounds containing substantially any arylsulfonyl radical can be used in the process of the invention and in the preparation of the corresponding arylsulfonyl intermediates and final products, the preferred starting materials and intermediate products are those containing the p-toluenesulfonyl radical due to the ready availability of the p-toluenesulfonyl halides and to the generally crystalline nature of the p-toluenesulfonyl' derivatives of compounds with which the present invention is concerned. The invention is, however, not limited to compounds containing the p-toluenesulfonyl radical and compounds containing other arylsulfonyl 5 ra'dieals, such as the befiz'enesulfonyl, io-tolu'ene sulfonyl, maphthalenesul'fonyl, methylnaphthalenesulfonyl radicals and others, can be used, if desired.

-It should also he mnti'oiied that compounds containin a fiylsiilfohm madman ha ving nen-hydroearbonsu-betituems ca'n he i'i's'e'd inthe process iiffd the corresponding intermediate fi'nal roducts prepared, provided *only that the substituent is r-io'rr rea'tive u' nd'er the rea'tion conditions. Such non-reactive substituents include chlorine, bromine, and the metnox yphenoxy, intro "and similar radicals. "It "should be mentioned further that, although the' present invention is concerned primarily with compounds wherein "the sulfo'nyl radical is an 'arylsulfonyl radical; the processjcan also-'be'carrietiout and the corresponding *produets prepared using S'fialtifig materials 'containing allr-ylsulfonyl, aralkylsub fon'yl =orcy1oa1k ls i1fony1 "radicals, such as the meth'anes'ulfonyl, 'ethane'siilfonyl, 'cyoloh'exylsiil fon'yl, and *pheriylm'ethanesulfonyl radicals.

The reaction or dialkyl "acetal bras-emopro'panm "with "an 1 'T- ary1su1fonyl) -*p-'aminohen- Zoateester can he "Carried 'out readily by heating thesnbstances'togethenm'referably with t'headdrti'on of a catalytic prop'or'tion of 'pyridi'ne'or" other tertiary amine. Approximately "equimol'ecnla'r proportions 'ofthe reactants canhe used and the mixture preferably heated at from "about 100 degrees to about 150 degrees Centigrade fio'r from abo'iitfi to QlbouflBOmimites. 'Th'e N-(3,3"dial k'oxy 2 -hydroxypropyl) N (aryl'snlfonyl)-paminobenz'o'at'e co'ni'pofih'diormed can' 'b'ei'solated fromthe reaction mixture, e. g. by Washingthe cru'ii'e reactionfpro duct thoroughly "with a suitable solvent, such as naphtha o'r isopropanol, "toremove the catalys't and iifnrea'cted starting materials. 'Some of the N-i3l3-iiialkoxy 2-hydroxypropyl) N ('arylsulfony-I) T-p-an'linobenz'oate esters are thus obtained as crystalline c'ompoiindshaving Well defined meltinghp'oints and some as sirupy liquids. "They can "be 'hyiirolyzed to the corresponding acids by mixing with aqueous alkalies or other conventional alkalinehydro'lytio agents and acidifying -the aqueous r'eaction mixtureQpreferablY W itha mineral acid. Certain of the acids'are thus obtained 'as-s-oliilsubstances.

New compounds representedhy the. genericformnla (IV) whic hcan'bevprepareii'by the methoii of the invention include arnongmany others, methyl N- (3,3-diethxy i 2 ketopropyll-litptoluenesul-fonyl) -p-aminobenzoate,iso=propyl N- 3,3-- di-n-hexoxy 2 ketopropyl) N'- (al phanaphthalenesulfony-l)-p-aminobenzoate, n-ootyl N (-33 --di-- n-octoxy --2 -'-ketopropy1) -N- tpethoxybenzenesulfonyl) p amino'benzoate, dimethyl N'- (N (3,3 -diethoxy-2-ketopropyl) N-(ptoluenesulfonylh-paminobenzoyl) rglutamatediiso-propyl N'- (N- (3,3-di-n-hexoxy 2 ketopropyl) N- (alpha riaphthalenesiilfonyl)'p aminobenzoyl) -glutamate, di n-ootyl N( N'-'(3,3-di=nnonoxy "2 ketopropyl) N'- (o 'chloro ipethoxybenzenesulfonyl) p :aminobenzoyl) glutamate, -"N-' (33 diethoxy ketopropyl) -'N- (ptoliienesulfonyl) epaminoben'zoic aci'd, :N 3,-3-din -:-hexoxy 2 letopropyl) N- (alpha-- naph thaleries'ulfonyl) p-"aminobenzoic -aeid, N- 3,3-di=- T glutariiic acid.

'u'enesulfonyl) -'p-aminobenzoate "and two drops of pyridine was heatedifortwelve minutes'at 'degrees to degreesC. The *cl'e'a'r' melt whichwals formedwas-cooled and-seeded with crystals of previously prepared ethyl N-(3j'3-diethoxy=2hydroxypro'pyl) -N (p toluenesulfonyl) -.paminobenzoate. The partially crystalline mass was triturated with-.a mixture ef-six millilitersot petroleum naphtha and three milliliters of isoprop'anol "and the mixture filtered. There was thus obtained "1.71 grams of ethyl --N-(3;3-diethoX-y 2- hydroxyp'ropyly- Nl (p--'toluen'esulfonyl-) -ipaminobenzoate melting-at 89 degrees to 94 degrees 0. Repeated. recrystallization of the product from 'i-so'propanol--petrolenm naphtha raised the melting .point to 91 degreesto 94'degrees C.

Following substantially the-same .procedure5h1it using an equi-molarproportion of the-:d-im'ethyl acetal of 2,3-oxidopropanal, the di-n-propyl acetal of 2,3-oxidopropanaljtheiii-n-butyl acetal of 2,3 -oxidopropanal, the di-isobutyl acetal of 2-,3- oiiiiiopropanal oror the iii-'iiodecyl 'act'a' l of '2',3- ozidopropanal in place of the diethyl'acetal of 2B-oxidopropahal, there are 'formed ethyl N-"(SBF dimethoxy 2 hydroxypropyl) "N (p tolu'en'esul'fon'yl') :p-aminohenzo'a'te, 'e'thyll N 't3'j3-die ne'prospoxy -2 hydroXyp'roWl) N "(,p lienesliliomil)ep aniinobenzoate, ethyl "N- ;3 'din-blitoxy -'2 hydroxypropyl) N (p toluen'estilfon yl) -p-amin6benzoate, ethyl N-(3','3 di-iso butoxy '2 -"h-y"droxypropyl) -"N '(p to1uen'esiilfonyl) ep aminobenzoate, and ethyl 'N-(3,3-d.idodec-yloxy 2 --"hydroxypropyl) N .(p-"tol: uenesulfonyl)p-aminobenzoate, respectively. "Following sii-bstaiitially'thesame proc'edurehrit using equi-molartproportions of ethyl Fri-"(benzenesvilfonyll =p-aniinobenzeate, n hexyl lT-(o t'o'lnenesulfohyl)-p-an'iinobenzoate, 'n-butyl N(pchloroberiaenesulfonyll p aminobenzoate, 01' 6f n doii'eoylll Kb'eta naphthalenesulf-ohyl) 1oaminobenzoate'in filace of theethyl- N-lp toluenesulfonyl)-p-aminobenzoate, there are obtained ethyl N 3 ,3 -'.'diethoxy- 2-hydroxyehropyl) N (ben- Empty-and nine tenthsigrams voiN-i p-ltoluenesulfonylbp aniinobenzoyl chloride "and 23!.9 grams of vdiethyl 11 eglutamate hydrochloride were dissolved in 300;milliliters of ethylene ilchloride and the solution cooled tobetween il degrees and'li) qlegrees C. The coldsolution was stirred.vigorously:and22;3gramsoftriethylamine in 72 milliliters of :ethylene dichloride was added slowly over a period of about 20 minutes. The temperature of the mixture was held between 10 degrees and degrees C. during the addition of the triethylamine and the mixture then allowed to stand at room temperature for one hour. The mixture was then washed successively with water, dilute hydrochloric acid, saturated aqueous sodium bicarbonate and finally with water. The colorless Solution thus obtained was dried with anhydrous sodium sulfate and naphtha was added until the solution became opalescent. The mixture was then cooled to cause crystallization and filtered. The crystals, after drying, consisted of 36 grams. of diethyl N-(N-(p-toluene sulfonyl) -p-aminobenzoyl) -l-glutamate melting at 124 degrees to 126 degrees C.

Example 3.Diethyl N -(N -(3,3-d2'ethoxy-2-hy dmzcypropyl) -N-(p-toluenesulfonyl) -p-aminobenzoyl) -1 glutamate One and six-tenths grams of the diethylacetal of 2,3-oxidopropanal and five drops of pyridine were added to 4.77 grams of fused diethyl N'-(N- (p"-' toluenesulfonyl) p aminobenzoyl) 1- glutamate at degrees C. The mixture was stirred for about 30 minutes at degrees to degrees C. The highly colored mass consisted chiefly of diethyl N'- (N-(3,3-diethoxy-2-hydroxypropyl) N (p toluenesulfonyl) p aminobenzoyD-l-glutamate. It had an index of refraction without further purification of Following substantially the same procedure, but using an equi-molar proportion of the dimethyl acetal of 2,3-oxidopropanal, the di-n-propyl acetal of 2,3-oxidopropanal, the di-n-butyl acetal of 2,3-oxidopropanal, the di-iso-butyl acetal oi 2,3-oxidopropanal or the di-dodecyl acetal of 2,3- oxidopropanal in place of the diethyl acetal of 2,3-oxidopropanal, there are obtained diethyl N (N (3,3 dimethoxy 2 hydroxypropyl) N- (p toluenesulfonyl) p aminobenzoyl) lglutamate, diethyl N (N- (3,3-di-n-propoxy-2- hydroxypropyl) N (p toluenesulionyl) paminobenzoyl) -l-g1utamate, diethyl N'-(N-(3,3- di n butoxy 2 hydroxypropyl) N .(ptoluenesulfonyl) p aminobenzoyl) 1 glutamate, ,diethyl N '-(N-(3,3-di-iso-butoxy-2-hydroxypropyl) N (p toluenesulfonyl) paminobenzoyl)-l-glutamate, and diethyl N-(N- (3,3 di dodecyloxy 2 hydroxypro'pyD-N- (p toluenesulfonyl) p aminobenzoyl) 1- glutamate, respectively.

Following substantially the same procedure, but using an equi-molar proportion of diethyl N '-(N- (benzenesulfonyl) p aminobenzoyl) l glutamate, di-n-hexyl N'- (N-(o-toluenesulfonyl) -paminobenzoyl)-1-glutamate, di-n-butyl N-(N- (p chlorobenzenesulfonyl) p aminobenzoyl) I-glutamate, or of di-n-dodecyl N'-(N-(betanaphthalenesulfonyl) p aminobenzoyl) 1- glutamate in place of diethyl N '-(N-(p-toluenesulfonyl) p aminobenzoyl) 1 glutamate, there are obtained diethyl N'-(N-(3,3-diethoxy 2 hydroxypropyl) N (benzenesulfonyl) paminobenzoyl)-l-glutamate, di-n-hexyl N'-(N- (3,3 diethoxy 2 hydroxypropyl) N (otoluenesulfonyl) p aminobenzoyl) 1 glutamate, di-n-butyl N (N- (3,3-diethoxy-2-hydroxypropyl) N (p chlorotoluenesulfonyD- p-aminobenzoyl)-1-glutamate and di-n-dodecyl N (N (3,3 diethoxy 2 hydroxypropyD- N (beta naphthalenesulfonyl) p aminobenzoyl) -1-g1utamate, respectively.

8 Example 4.-N-(3,3-dietho:cy-2-hydroxypropyl) N (p-toluenesulfonyl) -p-aminobenzoic acid A quantity of ethyl N-(3,3-diethoxy-2hydroxypropyl) N (p-toluenesulfonyl) -p-aminobenzoate is warmed for several minutes with slightly more than one molar portion of dilute aqueous or alcoholic sodium hydroxide and the mixture then cooled, diluted, acidified and filtered. There is thus obtained N-(3,3-diethoxy- 2 hydroxypropyl) N (p toluenesulfonyl) -paminobenzoic acid.

- Following substantially the same procedure ethyl N- 3,3-dimethoxy-2 hydroxypropyl) -N- ptoluenesulfonyl) -p-aminobenzoate, ethyl N-(3,3- di n propoxy-2-hydroxypropyl) -N-(p-toluenesulfonyl)-p-aminobenzoate, ethyl N-(3,3-di-nbutoxy-2 -hydroxypropyl) -N (p-toluenesulfonyl) p-aminobenzoate, ethyl N-(3,3-di-isobutoxy-2- hydroxypropyl) -N-(p-toluenesulfonyl) -p-aminobenzoate, butyl N-(3,3-di-dodecyloxy-2-hydroxypropyl) -N- (p-toluenesulfonyl) -p-amin0benzoate, n hexyl N (3,3-diethoxy-2-hydroxypropy1) -N- (o-toluenesulionyl)-p-aminobenzoate, n-dodecyl N (3,3 diethoxy 2 hydroxypropyl) -N-(betanaphthalenesulfonyl)-p-aminobenzoate, diethyl N' (N (3,3 diethoxy-2-hydroxypropyl) -N-(ptoluenesulfonyl) p-aminobenzoyl) -l-glutamate, di n butyl N'-(N-(3,3-diethoxy-2hydroxypropyl) N- (p-ch1orobenzenesulfonyl) -p-aminobenzoyl) -l-glutamate, diethyl N-(N-(3,3-diethoxy- 2 hydroxypropyl) N-(benzenesulfonyl) -p-aminobenzoyD-l-glutamate and di-dodecyl N'-(N- 3,3 diethoxy Z-hydroxypropyl) -N-(beta-naphthalenesulfonyl) p-aminobenzoyl) -l-glutamate are hydrolyzed to form N-(3,3-dimethoxy-2-hydroxypropyl) N (p-toluenesulfonyl) -p-aminobenzoic acid, N- (3,3-di-n-propoxy-2-hydroxypropyl) N (p-toluenesulfonyl) -p-aminobenzoic acid, N (3,3 di-n-butoxy-2-hydroxypropyl) -N- (p-toluenesulfonyl) -p-aminobenzoic acid, N- (3,3- di iso butoxy-2-hydroxypropyl) -N- (p-toluenesulfonyl) p aminobenzoic acid, N-(3,3-di-dodecyloxy 2 hydroxypropyl) N-(p-toluenesulfonyD-p-aminobenzoic acid, N-(3,3-diethoxy-2- hydroxypropyl) -N- (o-toluenesulfonyl) -p-aminobenzoic acid, N-(3,3-diethoxy-Z-hydroxypropyl) N beta naphthalenesulfonyl) -p-aminobenzoic acid, N (N-(3,3-diethoxy-2-hydroxypropyl) -N- (p-toluenesulfonyl) -p-aminobenzoyl) -l-glutamic acid, N (N -(3,3-diethoxy-2-hydroxypropyl) -N- (p chlorobenzenesulfonyl) -p-aminobenzoyl) -1- glutamic acid, N (N- (3,3-diethoxy-2-hydroxypropyl) N-(benzenesulfonyl) -p-aminobenzoyl) l-glutamic acid, and N'-(N-(3,3-diethoxy-2-hydroxypropyl) N- (beta-naphthalenesulfonyl) -p-' aminobenzoyl)-1glutamic acid, respectively.

Example 5.-Ethyl N-(3,3-diethoxy-2-ketopropyl) -N- (p-toluenesulfonyl) -paminobenzoate Approximately 3.2 grams of ethyl N- (p-toluenesulfonyl) -p-aminobenzoate was reacted with the diethyl acetal of 2,3-oxidopropanal by the method described in Example 1. The crude reaction mixture prior to seeding was dissolved in 10 milliliters of glacial acetic acid and the solution mixed with a solution of one gram of chromic anhydride in 20 milliliters of glacial acetic acid. The mixture was allowed to stand at room temperature for about three hours and the acetic acid distilled in vacuo. The residue was triturated with ether and the mixture filtered; The ethereal filtrate was washed with water, dried and the ether volatilized. The residue consisted of ethyl N-(3,3- diethoxy 2 -ketopropyl) -N- (p-toluenesulfonyl) 11 12 N-(p-toluenesulfonyl) -p-aminobenzoyl) 1 glu- 7. Diethyl N '-(N-( 3,3-diethoxy-2-ketopropyl) tamic acid, N-(N-(3,3-diethoxy-2-ketopropy1)- N-(p-toluenesulfonyl) -p-aminobenzoyl) gluta- N- (p chlorobenzenesulfonyl) -p-aminobenzoyl) mate. l-glutamic acid, N'-(N-(3,3-diethoxy-2-ketopro- 8. The method which includes: oxidizing an pyl) N (benzenesulfonyl) -p-am.inobenzoyl) -1- 5 hydroxy acetal having the formula (alkyl-O-MCH-UHOH-CHP-NGC0(NH47HCH2CH2COLOR' aryl-SO:

glutamic acid, and N'-(N-(3,3-diethoxy-2-ketowherein R i a member of the group consisting 'propyl)-N-(beta-naphthalenesulfonyl)-p-aminoof hydrogen and the alkyl radicals and n is a -benzoyl) -1-glutamic acid, respectively. member of the group consisting of zero and the The keto esters thus obtained are hydrolyzed by positive integer 1 to form a keto acetal having dilute alkali to form the corresponding keto acids. the formula 000R (alkyl-O-hCH-C o-cm-N comm ncmomcohon' aryl- O: I

It is to be understood that the invention is not 9. The method of claim 8 wherein n is zero and to be limited to the exact details of operation or R is an alkyl radical. exact compounds shown and described, as ob- 10. The method of claim 8 wherein n is the vious modifications and equivalents will be apparpositive integer 1 and R is an alkyl radical. ent to one killed in the art, and the invention is, 11. The method of claim 8 wherein the alkyl therefore, to be limited only by the scope of the radicals each contains less than 8 carbon atoms. appended claims. 12. The method of claim 8 wherein the arylsul- We claim: fonyl radical is the p-toluenesulfonyl radical. 1. A compound having the formula 13. The method of claim 8 wherein the hydroxy 000R (alkyl-O-JzCH-C o-cm-N o omncncmomo O).OR'

aryl-SO:

wherein R is a member of the group consisting acetal is ethyl N (3,3 diethoxy 2 --hydroxyof hydrogen and the alkyl radicals and n is a propyl) N (p toluenesulfonyl) p aminomember of the group consisting of zero and the benzoate.

positive integer l. 14. The method of claim 8 wherein the hydroxy 2. A compound as claimed in claim 1 wherein acetal is diethyl N-(N-(3,3-diethoxy-2-hydroxythe alkyl radicals each contains less than 8 carpropyl) N (p toluenesulfonyl) p aminobon atoms. benzoyl) -glutamate.

3. A compound as claimed in claim 1 wherein 15. The method which includes: oxidizing an R is an alkyl radical and n is zero. '4 hydroxy acetal ester having the formula GOO-alkyl (alkyl-0);CHCHOH-CH:N oo NHcHoH=omc0),.-0-a1r 1 aryl- O:

' 4. A compound as claimed in claim 1 wherein wherein n is a member of the group consisting of R is an alkyl radical and n is the positive inzero and the positive integer l to form a keto teger 1. acetal etser having the formula 5. A compound as claimed in claim 1 wherein and hydrolyzing the keto acetal ester with an the arylsulionyl radical is the p-toluenesulfonyl alkali to form a keto acetal acid having the forradical. mula coon (alkylO-)z cH-o O-CHr-N c owner-romaine 0),.011

aryl 01 6. Ethy] N-(3,3-diethoxy-2-ketopropyl)-N-(p- DAVID) I. WEISBLAT. toluenesulfonyl)-p-aminobenzoate. BARNEY J. MAGERLEIN.

No references cited.

Non-Patent Citations
Reference
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Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US5716990 *Sep 9, 1996Feb 10, 1998Cancer Research Campaign Technology LimitedDrug delivery systems
Classifications
U.S. Classification560/12, 560/10, 560/13, 562/430
Cooperative ClassificationC07D491/04