Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
  • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
  • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
  • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
  • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
  • C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
  • C07D251/16—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
  • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
  • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
  • C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
  • C07D251/22—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to two ring carbon atoms
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
  • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
  • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

• Hal is a halogen atom, preferably chlorine
• R is selected from the group consisting of hydrogen, alkyl of 1-6 carbon atoms and alkyl of 1-6 carbon atoms substituted by -OH, --OR -NHR -N(R or a halogen atom, R and R have the same significance as R and R and furthermore may be closed to a ring, possibly with the inclusion of a further heteroatom, such as piperazine, piperidine, phenoxazine, 9,10-dihydrophenazine or morpholine ring and R is selected from the group consisting of aryl such as phenyl and alkyl of 1-6 carbon atoms, R taken individually are aryl or alkyl of 1 to 6 carbon atoms and taken together can be closed to a ring with the nitrogen atom, possibly with inclusion of a further heteroatom, as described above with reference to R and R and Z is
• the invention relates to novel substituted s-triazines and a method
• R and R can be the same or different and are selected from the group consisting of hydrogen, alkyl 3,522,255 Patented July 28, 1970 ice of 16 carbon atoms and hydroxy alkyl of 1-6 carbon atoms; Y is selected from the group consisting of -0H3, GHzHa1, -OHHal2, 'CHal Hal, 0 R, SR and wherein Hal is a halogen atom, preferably chlorine, R is selected from the group consisting of alkyl of 1-6 carbon atoms and alkyl of l-6 carbon atoms substituted by OH, OR -NHR N(R or a halogen atom, R and R have the same significance as R and R and furthermore may be closed to a ring, possibly with the inclusion of a further heteroatom, such as a piperazine, piperidine, phenoxazine, 9,10-dihydrophenazine or preferably morpholine ring and R is selected from the group consisting of a piperazine,
• the new compounds can be prepared by saponifying compounds of the formula (I wherein R is alkyl or hydroxy alkyl of 1-6 carbon atoms or aryl or hydroxy aryl, in the presence of a water misci-- ble organic solvent, especially a lower alkanol, and preferably methanol, and in the presence of about molar quantities of barium hydroxide or sodium hydroxide, potassium hydroxide at a temperature between 0 C. and the boiling point of the solvent, preferably between about 50 and 70 C. to form a compound of Formula I.
• a water misci-- ble organic solvent especially a lower alkanol, and preferably methanol
• barium hydroxide or sodium hydroxide, potassium hydroxide at a temperature between 0 C. and the boiling point of the solvent, preferably between about 50 and 70 C.
• Y initially represents the group -CHal
• the compound can be reacted with an amine of the formula wherein R and R have the same significance as above to form compounds wherein Y is
• the latter reaction can, for example, be carried out in the presence of an alkali metal alcoholate, preferably in quantities of 0.1 to about 10 wt. percent at room or raised temperatures.
• an alkali metal alcoholate preferably in quantities of 0.1 to about 10 wt. percent at room or raised temperatures.
• a lower alkanol as solvent.
• the ratios of the compounds used for example, can be between 1:5
• the amine is a solid substance, it can first be dissolved in a small quantity of an organic solvent, such as, for example, acetone, ethyl acetate, dioxane or alkanols. If desired, the reaction can also be carried out in the presence of cathalytic quantities of water or alkali metal hydroxide. The reaction can be carried out at room temperature.
• an organic solvent such as, for example, acetone, ethyl acetate, dioxane or alkanols.
• the reaction can also be carried out in the presence of cathalytic quantities of water or alkali metal hydroxide. The reaction can be carried out at room temperature.
• the compounds used as starting materials can be prepared by the process described in German Pat. 1,189,999.
• the compounds according to the invention exhibit biological activity and can be used as herbicides and also, for example, as analgesic and antiphlogistic substances.
• the compounds for example, provide a strong antiphlogistic action on carrageen edema of the rats paw upon oral administration in dosages of 10-100 mg./kg.
• the following table indicates the arrest in carrageen edema of the rats paw upon oral administration of 30 mg./kg. of several illustrative compounds according to the invention (results in percent of edema arrest as compared to control group) and the acute toxicity of such compounds.
• the antiphlogistic action investigations were carried out according to the method of Domenjoz and Cll., Arch. Exp. Pharm. Path., 230, 325 (1957), and the acute toxicity tests were carried out according to the method of Miller & Tainter, Proc. Soc. Exper. Biol. and Med., 57, 261 (1944) with a 24 hour observation period.
• D 9220 Z-trichloromethyM-(l-methyl-l-hydroxy)-etl1yl-fi-morpholino-s-triazine.
• t D 9721 2-ethylamino i-(l-methyl-Lhydroxy)-ethyl-6-piperazino-sriazlne.
• EXAMPLE 1 50 g. of 2-trichloromethyl-4-morpholino-6-[ct-(carbethoxy-oxy)-et-methyl-ethyl]-s-triazine were dissolved in 300 ml. of methanol and the solution heated to boiling. 42 g. of Ba(OH) -8H O were dissolved in 400 ml. of hot methanol and such solution added to the triazine solution over a 3 hour period while the latter was constantly boiled. The triazine solution which initially was clear became cloudy as the saponification proceeded upon addition of the Ba(OH) solution. The reaction mixture was then boiled down without first separating the solids and the residue stirred up with dilute HCl whereupon CO was set free.
• EXAMPLE 2 85 g. of 2-trichloromethyl-4-ethylamino-6-[ct-(carbethoxy-oxy)-ot-methyl-ethyl]-s-triazine were dissolved in 300 ml. of methanol and heated to boiling.
• EXAMPLE 4 114 g. of 2-[a-(carbomethoxy-oxy-a-methyDethyl]- 4 morpholino 6 trichloromethyl s triazine (M.P. C.) were dissolved in 500 ml. of methanol and a solution of 90 g. of Ba(OH) -8H O in 750 ml. of methanol added thereto over a 30 minute period. The mixture was then refluxed for 1 /2 hours. The processing was described in Example 3.
• EXAMPLE 5 Analogously the following compounds (a) 2-(a-hydroxy-a-methyl)-ethyl-4-(3-methoxypropyl)- amino-6-trichloromethyl-s-triazine (M.P. 4l-43 C.)
• EXAMPLE 7 41.25 g. of 2-[ot-(carboethoxy-oxy)-tx-methyl-ethyl] 4- piperazino-6-trichloromethyl-s-triazine (0.1 mol) were heated to reflux with 161.6 g. (1.8 mols) 50 RC. aqueous ethylamine for 4 hours.
• reaction solution was then concentrated under vacuum and the residue dissolved in 200 ml. of methylene chloride.
• the solution was washed with water to extract the residue of ethylamine. Then the solution had been concentrated under vacuum.
• the residue yielded 22.3 g. of 2- [a-(carbethoxy-oxy) -a-methyl-ethyl] -4-piperazino-6-ethylamino-s-triazine which was 66% of theory. Its melting point was 9497 C.
• EXAMPLE 8 33.8 g. of 2-[ut-(carbethoxy-oxy)-u-methyl-ethyl]-4-piperazino 6-ethylamino-s-triazine (0.1 mol) were dissolved in 500 m1. of methanol and then a solution of 10 g. of
• EXAMPLE 10 E 36.2 g. of 2-[a-(carbethoxy-oxy)-a-methyl-ethy1]-4-N'- methyl-piperazino-6-ethylamino-s-triazine (0.1 mol, vis- 25 W111 be represented therein by the Symbol cous, produced according to Example 7 from 2-(m-carbethoxy oxy a-methyl-ethyl)-4-N'-methyl-piperazino-6- ethylamino-s-triazine (0.1 mol, viscous, produced accord- TABLE Example Starting Material End Product /C(CH5)2OCOC;H5 C(CHQa-OTI 1 O13C 0130-4 ⁇ N H 0 ⁇ N/ H 0 C(GHQzOfiOCgH a O(OH2)2OH 0 2 Cl3C-- 0130- ⁇ NHCQILI, NHCgH C(CHQEOEOCZH C(CHmOH Imam-
• the substituted s-triazine of claim 1 which has the 1.
• R is selected from the group consisting of hydrogen, lower alkyl of l to 6 carbon atoms and lower alkyl of 1 to 6 carbon atoms substituted with a substituent selected from the group consisting of OH, -OR -NHR N(R and Hal, Hal signifies a halogen atom
• R and R have the same meaning as R and may be the same or different with the proviso that only one of these two radicals shall be said substituted alkyl and wherein R and R together may form cyclohexyl, piperazino, N'-methyl-piperazino or piperidino
• R is selected from the group consisting of phenyl and lower alkyl of 1 to 6 carbon atoms
• R is selected from the group consisting of wherein R and R have the same significance as above; and their pharmaceutically acceptable acid addition salts.
• each of R and R are selected from the group consisting of hydrogen, lower alkyl of 1 to 6 carbon atoms and lower alkyl of 1 to 6 carbon atoms substituted by a member selected from the group consisting of References Cited UNITED STATES PATENTS 2,887,409 5/1959 Van Loo 260-249.9 XR 2,926,165 2/1960 Shapiro et al. 260-2499 HENRY R. JILES, Primary Examiner J. M. FORD, Assistant Examiner US. Cl. X.R. 260-249.5, 999

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• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Plural Heterocyclic Compounds (AREA)

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Citations (2)

• 1965
  • 1965-10-30 DE DE19651545753 patent/DE1545753A1/de active Pending
• 1966
  • 1966-09-30 CH CH1419666A patent/CH478130A/de not_active IP Right Cessation
  • 1966-10-19 FR FR80579A patent/FR1502959A/fr not_active Expired
  • 1966-10-20 NL NL6614788A patent/NL6614788A/xx unknown
  • 1966-10-26 GB GB47997/66A patent/GB1122524A/en not_active Expired
  • 1966-10-26 BE BE688933D patent/BE688933A/xx unknown
  • 1966-10-31 US US594647A patent/US3522255A/en not_active Expired - Lifetime
• 1967
  • 1967-01-19 FR FR91778A patent/FR6242M/fr not_active Expired
• 1970
  • 1970-06-01 US US42488A patent/US3684806A/en not_active Expired - Lifetime

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