NO753480L - - Google Patents

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Publication number
NO753480L
NO753480L NO753480A NO753480A NO753480L NO 753480 L NO753480 L NO 753480L NO 753480 A NO753480 A NO 753480A NO 753480 A NO753480 A NO 753480A NO 753480 L NO753480 L NO 753480L
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Norway
Prior art keywords
formula
pyrimidine
diamino
water
hydroxy
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NO753480A
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Norwegian (no)
Inventor
P Bamberg
L J S Vegh
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Astra Pharma Prod
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Publication of NO753480L publication Critical patent/NO753480L/no

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C07D239/49—Two nitrogen atoms with an aralkyl radical, or substituted aralkyl radical, attached in position 5, e.g. trimethoprim
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)

Description

Oppfinnelsen angår en ny fremgangsmåte for fremstilling av' 2 , 4-diamino-6-hydroksy-5-(3',4',5'-trimetoksybenzyl)-pyrimidin med formel I: The invention relates to a new process for the preparation of 2,4-diamino-6-hydroxy-5-(3',4',5'-trimethoxybenzyl)-pyrimidine with formula I:

Det er kjent at forbindelsen med formel I er et verdi-fullt mellomprodukt for fremstilling av trimetoprim, d.v.s. It is known that the compound of formula I is a valuable intermediate for the production of trimethoprim, i.e.

2 ,4-diamino-5-(3 ' , 4 ' , 5 '-trimetoksybenzyl)-pyrimidin. Trimetoprim 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine. Trimethoprim

har antibakteriell og sulfonamid-potensierende virkning (B. Roth et al., J. Med. Pharm. Chem. 5, 1103/1962, og S.R.M. Bushby og G.M. Hit.bhings, Brit. J. of Pharm. Chem. 33, 72/1968). has antibacterial and sulfonamide-potentiating action (B. Roth et al., J. Med. Pharm. Chem. 5, 1103/1962, and S. R. M. Bushby and G. M. Hit.bhings, Brit. J. of Pharm. Chem. 33, 72 /1968).

1 henhold til fremgangsmåter som er beskrevet i den tekniske litteratur kan forbindelser med formel I fremstilles i det vesentlige på to måter: a) I tysk utlegningsskrift OLS 2.003-578 (1970) beskri-ves en fremgangsmåte hvorved en cyaneddiksyrealkylester omsettes 1 according to methods described in the technical literature, compounds of formula I can be prepared essentially in two ways: a) In German explanatory document OLS 2.003-578 (1970) a method is described whereby a cyanoacetic acid alkyl ester is converted

med 3,4,5-trimetoksybenzylklorid til 3,4,5-trimetoksybenzyl-cyaneddiksyrealkylester. Denne forbindelse blir derpå kondensert med guanidin til en forbindelse med formel I. with 3,4,5-trimethoxybenzyl chloride to 3,4,5-trimethoxybenzyl cyanoacetic acid alkyl ester. This compound is then condensed with guanidine to a compound of formula I.

Enkelte av ulempene ved denne fremgangsmåte er at 3,4,5-trimetoksybenzylklorid er en kostbar forbindelse og at det dannes flere biprodukter som vanskelig kan separeres. Arbeids-eksemplene ifølge utlegningsskrift 2.003.578 er i virkeligheten ikke reproduserbare, man får bare råblandinger når man går frem som beskrevet i eksemplene. Some of the disadvantages of this method are that 3,4,5-trimethoxybenzyl chloride is an expensive compound and that several by-products are formed which are difficult to separate. The working examples according to explanatory note 2,003,578 are in reality not reproducible, you only get raw mixtures when you proceed as described in the examples.

b) Tysk utlegningsskrift OLS 2.165-362 (1972) beskriver en fremgangsmåte hvor 3,4,5-trimetoksybenzaldehyd omsettes med cyaneddiksyreaibkylester under dannelse av alkyl-a-cyano-3-(3j4j5-trimetoksyfenyl)-akrylat som derpå hydrogeneres til 3>4,5-trimetoksybenzyl-cyaneddiksyre-alkylester. Forbindelsen konden-seres med guanidin på samme måte som under prosess a). b) German explanatory document OLS 2.165-362 (1972) describes a method in which 3,4,5-trimethoxybenzaldehyde is reacted with cyanodeoxyreayl alkyl ester to form alkyl-a-cyano-3-(3j4j5-trimethoxyphenyl)-acrylate which is then hydrogenated to 3>4 ,5-trimethoxybenzyl cyanoacetic acid alkyl ester. The compound is condensed with guanidine in the same way as during process a).

Enkelte av ulempene ved denne fremgangsmåten er at den krever tre trinn og at det er vanskelig å gjenvinne uomsatt 3j4j5-trimetoksybenzaldehyd fra reaksjonsblandingen. Syntese-utbyttet er mindre enn i henhold til den foreslåtte fremgangsmåte. Some of the disadvantages of this method are that it requires three steps and that it is difficult to recover unreacted 3j4j5-trimethoxybenzaldehyde from the reaction mixture. The synthesis yield is less than according to the proposed method.

Foreliggende oppfinnelse er basert på den oppdagelse at 2j4-diamino-6-hydroksypyrimidin med formel II: The present invention is based on the discovery that 2j4-diamino-6-hydroxypyrimidine of formula II:

kan omsettes med 3,4,5-trimetoksybenzaldehyd hvorved man over-raskende danner en ny forbindelse med formel III: i godt utbytte. Nevnte forbindelse 2,4-diamino-6-okso-5~(3',4',5'-trimetoksybenzyliden)-pyrimidin, som etter reaksjonen fås som et kompleks av en ekvivalent 2,4-diamino-6-hydroksy-pyrimidin og en ekvivalent vann can be reacted with 3,4,5-trimethoxybenzaldehyde whereby a new compound of formula III is surprisingly formed in good yield. Said compound 2,4-diamino-6-oxo-5~(3',4',5'-trimethoxybenzylidene)-pyrimidine, which after the reaction is obtained as a complex of an equivalent 2,4-diamino-6-hydroxy-pyrimidine and one equivalent of water

blir deretter katalytisk hydrogenert til forbindelsen med formel I. Forbindelsen med formel I kan omsettes med godt utbytte til trimetoprim, f.eks. i henhold til ovennevnte utlegningsskrift is then catalytically hydrogenated to the compound of formula I. The compound of formula I can be converted with good yield to trimethoprim, e.g. in accordance with the above-mentioned specification document

2.003-578 og 2.165.362. (Disse metoder bygger på å erstatte 6-hydroksygruppen med klor i forbindelse med formel I, f.eks. med fosforoksyklorid. 6-klorgruppen blir derpå fjernet ved katalytisk hydrogenering). 2,003-578 and 2,165,362. (These methods are based on replacing the 6-hydroxy group with chlorine in connection with formula I, e.g. with phosphorus oxychloride. The 6-chloro group is then removed by catalytic hydrogenation).

Ovenstående reaksjonsvei er uventet, blant annet av den grunn at man ville anta at benzaldehydet reagerte med pyrimidinets aminogrupper. For eksempel vet man at 2-amino-4-hydroksypyrimidin reagerer med benzaldehyd under dannelse av en Schiffsk base (se J.A.C.S. 34, 554 (1905))og mange andre-eksempler på reaksjoner mellom aldehyder og aminogrupper i amino-substituerte pyrimidiner er beskrevet i den kjemiske litteratur: Dymickly, Caldwell, J.Org.Chem. 27, 4211 (1962), Klotzer, Herzberg, Monatshefte, 76, I567 (1965), Mc. Leod, J. Res. Nat. Bur. Stand., 66A, 65 (1962), Miura, Ikeda, Oohashi, Igarashi, Okada, Chem. Pharm. Bull, 13, 529 (1965), Kaye, Kogan, Ree. The above reaction pathway is unexpected, partly because one would assume that the benzaldehyde reacted with the pyrimidine's amino groups. For example, it is known that 2-amino-4-hydroxypyrimidine reacts with benzaldehyde to form a Schiff base (see J.A.C.S. 34, 554 (1905)) and many other examples of reactions between aldehydes and amino groups in amino-substituted pyrimidines are described in the chemical literature: Dymickly, Caldwell, J.Org.Chem. 27, 4211 (1962), Klotzer, Herzberg, Monatshefte, 76, I567 (1965), Mc. Leod, J. Res. Nat. Cage. Stand., 66A, 65 (1962), Miura, Ikeda, Oohashi, Igarashi, Okada, Chem. Pharm. Bull, 13, 529 (1965), Kaye, Kogan, Ree.

Trav. Chim. 71, 309 (1952), Lincoln, Heinzelman, Hunter, J.Am. Chem. Soc. 71, 2902 (1949). Trot. Chim. 71, 309 (1952), Lincoln, Heinzelman, Hunter, J. Am. Chem. Soc. 71, 2902 (1949).

Oppfinnelsen angår en fremgangsmåte for fremstilling av 2,4-diamino-6-hydroksy-5-(3 ' , 4 ' , 5 '-trimetoksybenzyl)-pyrimidin med formel I,'og karakteriseres ved at man i et oppløsningsmiddel omsetter 2,4-diamino-6-hydroksy-pyrimidin som har formel II med 3,4,5-trimetoksybenzaldehyd fulgt av katalytisk hydrogenering av den fremstilte nye forbindelse med formel III. The invention relates to a process for the preparation of 2,4-diamino-6-hydroxy-5-(3', 4', 5'-trimethoxybenzyl)-pyrimidine of formula I,' and is characterized by reacting 2,4 -diamino-6-hydroxy-pyrimidine having formula II with 3,4,5-trimethoxybenzaldehyde followed by catalytic hydrogenation of the new compound of formula III prepared.

Forbindelsene med formel III og IV utgjør en annen side ved oppfinnelsen. The compounds of formulas III and IV constitute another aspect of the invention.

Utgangsstoffene 2,4-diamino-6-hydroksy-pyrimidin og 3,4,5-trimetoksybenzaldehyd er velkjente kjemiske reagenser. Metoder til syntese av disse er beskrevet i f.eks. Org. Synth. Coll Vol. 4, 245-246 (1963) og i belgisk patent 789-586, respektivt. The starting materials 2,4-diamino-6-hydroxy-pyrimidine and 3,4,5-trimethoxybenzaldehyde are well-known chemical reagents. Methods for the synthesis of these are described in e.g. Org. Synth. Coll Vol. 4, 245-246 (1963) and in Belgian Patent 789-586, respectively.

Teoretisk kreves 0,5 ekvivalenter aldehyd og 1 ekvivalent pyrimidin for fremstilling av produktet med formel IV. Theoretically, 0.5 equivalents of aldehyde and 1 equivalent of pyrimidine are required for the preparation of the product of formula IV.

Ved den foreslåtte fremgangsmåte er det en fordel åt all pyrimidin omsettes. Av denne grunn kreves en mengde på ca. 0,6 ekvivalenter aldehyd for å gjennomføre reaksjonen kvantitativt innenfor et godtagbart tidsrom. En godt tørket prøve av pyrimidinet inneholder 0-1 ekvivalent krystallvann. Det er derfor en fordel å benytte pyrimidinet som det er og knytte alle angivelser'av utbyttet til det forbrukte og kostbarere benz aldehyd. All uomsatt aldehyd kan gjenvinnes ved enkel utvasking av råproduktet med varm toluen. Det gjenvundne aldehyd kan brukes på nytt. Den enkle og effektive gjenvinning av uomsatt aldehyd er en av fordelene med den foreliggende fremgangsmåte. In the proposed method, it is an advantage that all the pyrimidine is converted. For this reason, a quantity of approx. 0.6 equivalents of aldehyde to carry out the reaction quantitatively within an acceptable period of time. A well-dried sample of the pyrimidine contains 0-1 equivalent of crystal water. It is therefore an advantage to use the pyrimidine as it is and link all indications of the yield to the consumed and more expensive benzaldehyde. All unreacted aldehyde can be recovered by simply washing out the crude product with hot toluene. The recovered aldehyde can be reused. The simple and effective recovery of unreacted aldehyde is one of the advantages of the present method.

Omsetningen mellom aldehyd og pyrimidin kan skje i forskjellige oppløsningsmidler som vann, etanol/vann, vandig eddiksyre, vandig natriumhydroksyd, metylcellosolv, dimetylsulf-oksyd, etylenglykol, dioksan eller blandinger av disse. Minimal mengde kokende vann er det mest egnede oppløsningsmiddel,. The reaction between aldehyde and pyrimidine can take place in various solvents such as water, ethanol/water, aqueous acetic acid, aqueous sodium hydroxide, methylcellosolve, dimethylsulfoxide, ethylene glycol, dioxane or mixtures thereof. A minimal amount of boiling water is the most suitable solvent.

Reaksjonstemperaturen velges fortrinnsvis innenfor området 50 - 150°C. I kokende vann er reaksjonen kvantitativ etter 6-10 timer. Fortrinnsvis utføres reaksjonen i en autoklav og under inert atmosfære som f.eks. nitrogen. The reaction temperature is preferably chosen within the range 50 - 150°C. In boiling water, the reaction is quantitative after 6-10 hours. Preferably, the reaction is carried out in an autoclave and under an inert atmosphere such as e.g. nitrogen.

Den påfølgende katalytiske hydrogenering av forbindelsen med formel IV gjennomføres fortrinnsvis i en autoklav og ved overatmosfærisk trykk, f.eks. 1-8 atmosfærer. Man kan bruke forskjellige oppløsningsmidler. Et oppløsningsmiddel av metylcellosolv/vann (3:1) har vist seg særlig egnet. Palladium-på-trekull er en god katalysator. Reduksjonen foregår kvantitativt mindre syntesetap skyldes ufullstendig separasjon av sluttpro-duktet fra pyrimidinet som bindes i forbindelsen med formel IV og som frigjøres ved hydrogenering. The subsequent catalytic hydrogenation of the compound of formula IV is preferably carried out in an autoclave and at superatmospheric pressure, e.g. 1-8 atmospheres. Different solvents can be used. A solvent of methylcellosolv/water (3:1) has proven particularly suitable. Palladium-on-charcoal is a good catalyst. The reduction takes place quantitatively less loss of synthesis is due to incomplete separation of the end product from the pyrimidine which is bound in the compound with formula IV and which is released by hydrogenation.

Fremgangsmåten i henhold til foreliggende oppfinnelse illustreres ved de følgende eksempler. The method according to the present invention is illustrated by the following examples.

Fremstilling av 2,4-diamino-6-hydroksy-5-(3',4',5'-trimetoksy-benzyl )zEyrimidin Preparation of 2,4-diamino-6-hydroxy-5-(3',4',5'-trimethoxy-benzyl)zEyrimidine

a) 2,4-diamino-6-hydroksypyrimidin (31s5g = 230 mmola) 2,4-diamino-6-hydroxypyrimidine (31s5g = 230 mmol

- 250 mmol, inneholdende 0-1 ekvivalenter vann) oppløses i vann - 250 mmol, containing 0-1 equivalents of water) dissolve in water

(300 ml) ved badtemperatur, 115°C. 3,4 ,5-trimetoksybe.nzaldehyd (29,4 g = 150 mmol) tilsettes i en porsjon og reaksjonssuspen-sjonen røres i 20 timer ved 115°C under nitrogenatmosfære. Det avdampede vann (100 ml), den avkjølte reaksjons-suspensjon filtreres og filteret vaskes med ovenstående destillat (100 ml). Filteret tørkes ved 60°C/100 Torr og suspenderes i 400 ml varm toluen. Suspensjonen røres ved 100°C i 1 time og filtreres varm. Dette gjentas en gang med filter. Filteret tørkes ved 60°C/ (300 ml) at bath temperature, 115°C. 3,4,5-trimethoxybenzaldehyde (29.4 g = 150 mmol) is added in one portion and the reaction suspension is stirred for 20 hours at 115°C under a nitrogen atmosphere. The evaporated water (100 ml), the cooled reaction suspension is filtered and the filter is washed with the above distillate (100 ml). The filter is dried at 60°C/100 Torr and suspended in 400 ml of hot toluene. The suspension is stirred at 100°C for 1 hour and filtered hot. This is repeated once with the filter. The filter is dried at 60°C/

L0.0, Torr og gir 48 g rent 2 ,4-diamino-6-okso-5" (3 ' ,4 ' ,5 '-tri-metoksybenzyliden)-pyrimidin som er kompleksdannet til en ekvivalent 2,4-diamino-6-hydroksypyrimidin og en ekvivalent vann, sm.p. 291-293°C. L0.0, Dry and gives 48 g of pure 2,4-diamino-6-oxo-5"(3',4',5'-tri-methoxybenzylidene)-pyrimidine which is complexed to an equivalent of 2,4-diamino- 6-hydroxypyrimidine and one equivalent of water, mp 291-293°C.

Toluenfiltratet ekstraheres med ovenstående vandige filtrat. Toluensjiktet inndampes til tørrhet. Det leverer 7,7 g uomsatt 3^4,5-trimetoksybenzaldehyd som kan brukes på nytt til videre reaksjoner. Nettoutbyttet er 96,7 The toluene filtrate is extracted with the above aqueous filtrate. The toluene layer is evaporated to dryness. It delivers 7.7 g of unreacted 3^4,5-trimethoxybenzaldehyde which can be reused for further reactions. The net yield is 96.7

Analyse: C]_8H24N8°6:Analysis: C]_8H24N8°6:

Beregnet: C 48,21 H 5,39 N 24,98 %Calculated: C 48.21 H 5.39 N 24.98%

Funnet: C 47,90 H 5,39 N 24,94 % b) 2,4-diamino-6-okso-5-(3',4',5'-trimetoksybenzyliden)-pyrimidin (31,7 g = 70,6 mmol, inneholdende en ekvivalent 2,4-diamino-6-hydroksypyrimidin og en ekvivalent vann) og fremstilt som ovenfor, ble oppløst i 600 ml metylcellosolv og 200 ml vann og hydrogenert med 5 g 10 % ig palladium-på-trekull i 16 timer ved -80°C og 5 at. Den avkjølte suspensjon filtreres på silika-gel og filteret vaskes med 100 ml varm metylcellosolv-vann = 3:1. Filtratet inndampes og inndampningsresten tørkes ved 60°C /100 Torr. Man tilsetter vann (100 ml) til inndampningsresten og suspensjonen røres i 1 time ved 100°C. Man lar suspensjonen avkjøle til 65°C og filtrerer den. Filteret vaskes med 50 ml vann som holder 65°C og tørkes ved 60°C/100 Torr. Man får 20,1 g 2,4-diamino-6-hydroksy-5-(3',4',5'-trimetoksybenzyl)-pyrimidin i utbytte 93 %. Sm.p. 275-276°C. Found: C 47.90 H 5.39 N 24.94% b) 2,4-diamino-6-oxo-5-(3',4',5'-trimethoxybenzylidene)-pyrimidine (31.7 g = 70 .6 mmol, containing one equivalent of 2,4-diamino-6-hydroxypyrimidine and one equivalent of water) and prepared as above, was dissolved in 600 ml of methylcellosolve and 200 ml of water and hydrogenated with 5 g of 10% ig palladium-on-charcoal in 16 hours at -80°C and 5 at. The cooled suspension is filtered on silica gel and the filter is washed with 100 ml of warm methylcellosolv water = 3:1. The filtrate is evaporated and the evaporation residue is dried at 60°C /100 Torr. Water (100 ml) is added to the evaporation residue and the suspension is stirred for 1 hour at 100°C. The suspension is allowed to cool to 65°C and filtered. The filter is washed with 50 ml of water at 65°C and dried at 60°C/100 Torr. 20.1 g of 2,4-diamino-6-hydroxy-5-(3',4',5'-trimethoxybenzyl)-pyrimidine is obtained in a yield of 93%. Sm.p. 275-276°C.

En prøve'acetyleres i pyridin og eddiksyreanhydrid og gir 2,4-diacetylamino-6-hydroksy-5-(3',4',5'-trimetoksybenzyl)-pyrimidin. Acetylderivatet ble mikroanalysert. A sample is acetylated in pyridine and acetic anhydride to give 2,4-diacetylamino-6-hydroxy-5-(3',4',5'-trimethoxybenzyl)-pyrimidine. The acetyl derivative was microanalyzed.

Beregnet for<C>^<H>^<N>^<Og:>C 55,38 % H 5,68 % N 14,38 % Funnet: C 55,47 % H 5,65 % N 14,40 % Calculated for<C>^<H>^<N>^<Og:>C 55.38% H 5.68% N 14.38% Found: C 55.47% H 5.65% N 14.40%

Filtratet inneholdt ca. 9 g 2,4-diamino-6-hydroksy-pyrimidin som kan brukes på nytt for omsetning med 3',<l>4,5-trimetoksybenzaldehyd (første trinn) og gir 14 g 2,4-diamino-6-okso-5-(3',4',5'-trimetoksybenzyliden)-pyrimidin. The filtrate contained approx. 9 g of 2,4-diamino-6-hydroxy-pyrimidine which can be reused for reaction with 3',<l>4,5-trimethoxybenzaldehyde (first step) and gives 14 g of 2,4-diamino-6-oxo- 5-(3',4',5'-trimethoxybenzylidene)-pyrimidine.

Claims (4)

1.' Fremgangsmåte for fremstilling av 2,4-diamino-6-hydroksy-5-(3_^,4 ' ,5 '-trimetoksybenzyl)-pyrimidin med formel I: 1.' Process for the preparation of 2,4-diamino-6-hydroxy-5-(3-^,4',5'-trimethoxybenzyl)-pyrimidine of formula I: karakterisert ved at man i et oppløsningsmiddel omsetter 2,4-diamino-6-hydroksypyrimidin med formel II: characterized in that 2,4-diamino-6-hydroxypyrimidine with formula II is reacted in a solvent: med 3j 4,5-trimetoksybenzaldehydj og katalytisk hydrogenerer den således fremstilte nye forbindelse med formel III: with 3j 4,5-trimethoxybenzaldehydej and catalytically hydrogenates the thus produced new compound of formula III: 2. Fremgangsmåte som angitt i krav 13karakterisert ved at oppløsningsmidlet består av kokende vann. 2. Method as stated in claim 13, characterized in that the solvent consists of boiling water. 3. Forbindelse med formel: 3. Connection with formula: 4. Forbindelse med formel: 4. Connection by formula:
NO753480A 1974-10-21 1975-10-15 NO753480L (en)

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SE7413202A SE400077B (en) 1974-10-21 1974-10-21 A PROCEDURE FOR THE PREPARATION OF 2,4-DIAMINO-5 (3 ', 4', 5 ', - TRIMETHOXYBENZYL) -PYRIMIDINE

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DK (1) DK135375B (en)
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FR (1) FR2299326A1 (en)
GB (1) GB1526235A (en)
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DE3365869D1 (en) * 1982-07-30 1986-10-09 Smith Kline French Lab Amino pyrimidinones and their preparation
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SE400077B (en) 1978-03-13
CH599168A5 (en) 1978-05-12
DK135375B (en) 1977-04-18
DK135375C (en) 1977-10-17
ATA788475A (en) 1977-09-15
NL7512341A (en) 1976-04-23
DK465375A (en) 1976-04-22
LU73620A1 (en) 1976-08-19
FR2299326B1 (en) 1978-10-13
FI752900A7 (en) 1976-04-22
JPS5165776A (en) 1976-06-07
FR2299326A1 (en) 1976-08-27
GB1526235A (en) 1978-09-27

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