SU468421A3 - "Method for the preparation of phthalazone-1 derivatives - Google Patents

Description

(54) METHOD FOR OBTAINING DERIVATIVES OF PHTHALAZONE-1

A method is proposed for the preparation of the starting compounds of phthalazane derivatives of formula 1:

about

OisOCNHRt

de ri -

Pril my silt “branched aldayl, dicloalkyl, alkenyl, aryl, aral kil, dialkyl aminoalkyl-il, furfuryl, 1P | I1K-ol1Il OR | P1p1Idil; R2 (water a, alkyl, ar l, “arbamoyl, K-aluyl1c | bams1, N, Nd, and a L KILk b am oyl, alkil1Sulphonyl ar | ilsulfon1il;

Rs atoms: m hydrogen or halogeka, alkyl OR alkasysprulpa;

R4 atom (HYDROXIDE OF HYLOGEN, ALKYL OR ALKAKOI, AVDINO, ACYLAMYO- AND AL (COCHIC ARB) THEY ln a and l

carbamobile gru.lpa.

These compounds have the valuable physical characteristics of the properties of aM (I.P. unavan method of car preparation, ba-matov. Mutual alcohols -: isocyanatam-i.

The proposed method is that the compound of the general formula 2

Rx CH, OH .. X

y

-R.

where RI has the indicated meanings. Lod1 converse. interaction with the isocyanate of formula 3

RiNCO,

rDi has the indicated meanings.

With the implementation of both the method and the method, the reaction of 1B3 and 1Modeist1B1 and the compounds of formula 2 is carried out with the EC-IMOLAR or excess CiBOM (1.2-2 mol) of the isocyanate of formula 3 in an Inert solvent or diluent, such as benzene, toluene, chlorobenzene, acetone) , chloroform. m, unisan, getragi.drofuran n ILI PyrI1Di. Preferably, this reaction is carried out at a temperature from room temperature to 150 ° C, especially at a temperature below 100 ° C. If the reaction is hydrated | at 50-i00 ° C, it completes at an interval of 1-5 hours If you use reactive scans, they are used at a room temperature (a standpoint of 1 st), its duration is 5–24 hours per hour. In case of inconsistency, the MOH1NO target used is a catalyst (such as CML trimethyl.min, triethyl MI: , X-alkyl-pisperidin or lir dId. Instead of isocyanates of general formula 3, there can be 1 yr of 1 van, compounds that can be pre geoscheny. in. oschmanaty general formula 3, under the conditions: t.rozede1-sh reactionin, :: ph of necessity, you can also use the kata: the congestion of the beam and isocyanate directly in the reaction medium. Ta: k, for the receiving (nziocyanate can be subjected to nalivane acylaseId of general formula RjCON where RI has the indicated values, or 5-alkylthiocarboxylic compounds of the general formula Vdas-8-A1k where RI has fixed values, excluding the hydrogen atom; Aik is a lower alkyl radical, such KajK methyl ll. And ethical / cal. In addition, 5-alkylthio (Carbamate can be used in the presence of tr, ialkilnna and salts of heavy metal, covertly as silver nitrate. The product can be isolated and cleaned by ordinary. MI cnioco6aj fH. PIMbf 1. In ipacTiBop 5 g 4-oxyadyl 1-phthalazone in 100 ml of dry pyridin Idina is added 2 g; methyl lysocia "ata. PacTiBop" Stayed on the daughter at the same temperature, then cooked at 80 ° C for 1 hour in a water batch. Then The iriyain is distilled under reduced pressure, the residue is subjected to lerecrystallization from methyl alcohol, and 5 g are obtained with 4- (M-methyl carbs 01 Xyme1Il) -1 Phetazone, mp 230-232 ° C. Found: C, 56.26; H, 4.70; 18.06; CncO3. Calculated,%: C, 56.65; H, 4.75; N 18.02. 2. To a solution of 3 g of 7-bram-4-0 | Xymethyl-2-methyl-1-phthalazone IB, 6 ml of dry pyridine is added 1.3 g of methyl isocyanate. After that, ipacTiBop is left overnight at night: room The temperature was measured with P1next and anaNateBaiHHeiM.It was 80 ° C for 30 minutes, then the solution was scrubbed at a lower pressure, the remainder was drawn through a mixture of petroleum acetate and petroleum efflux | 0m, and 3 g 7-br01M were obtained. 4- {X-methylcarbamox:; methyl) -2-methi.t-1-phthalazole, so pl. 181-183 ° C. Found,%: C 44.46; H 3.49; N 13.01. C-HiaOsNcBr. Calculated,%: C, 44.17; And 3.68; N 12.88. Example 3. 3 g of 4-0 Xymet; IL-1-phthalazone and 5 g of 3-l1Crid / AND carboxyl azide are dissolved in 40 ml of hydrous sodium npridine. After this, the temperature of the reaction mixture is increased. In a stepwise manner: | p1 = but up to 100 ° C and the mixture is kept at this temperature for 40 minutes. Next, the recovery solution is boiled under reflux at a fridge at 125 ° C for 8 hours. Pyridine is distilled off from the reaction mixture — a mixture of n-Kanech precipitate — is subjected to chemical treatment of acetone. 2.8 g of 4- (H-p-Pyridylcarbads-1XImetpl) -1ftalazoa are obtained, tl. 194-196 ° C. Found,%: C 60.42; H 4.27; N 19.00. C, 5H120zM4. Calculated,%: C 60.80; H 4.08; N 18.91. Example 4. 4 g of 4-oxime-Bil-1-phthalazone, 6 g of 5- | Methyl-N-a.-furfurylthio-1-carbamate and 3 g of triethylamine are added to pacTiBOp 40 ml of pyridine with 10 ml of aceto-nitro-ml. After that, a solution of 5.2 g of silver nitrate 1B of 10 ml of acetovitrile with one time and cooling is added to the indicated solution | After completion of the addition, the reactive CiO1nnuyu CiMecb was left: for 24 hours, followed by: heating three to 100 ° C, for 2 hours. After cooling, the reaction mixture was diluted with chloroform and the precipitate separated from the solution. The chloroform is washed with water and distilled off. The residue obtained is subjected to recrystallization from a mixture of ethyl alcohol and water to obtain 3 g of 4- (M-cc-furfurylcarbaMoxy-methyl) -phthalazone, so pl. 182-184 ° C. Found,%: C 60.03; H 4.25; N 14.34. C, 5H, ZO4Mz. Calculated,%: C 60.19; H 4.38; N 14.34. Examples 5-38. The compounds given in Table 1 are obtained analogously to Exampleraad. one.

P.P. Mer. 39. To ipacTiBCipy 4 g of 4 -0101XIMetil1-phthalazo and in 80 ml of pyridine add loka: pl m 3 g of p-dimethyl MI (Noethyl1iso.Tsi-1nat with stirring. The reaction mixture is left three the temperature is very low and then heated for 1 hour; a water bath at 100 ° C. Pyridin is replenished, under a umanshenny day, then (M residue: first install, come out of ethyl acetate and get 5 g ((3-dimethylamio-ethyl) ca-r ba mokaimethyl - ftalazo, on, llav shchessss inpii 148-150 ° C. Found: C 57.87; H 6.23; N 19.36.

C14H, 80eM4.

Calculated,%: C 57.62; H 6.25; N 19.30.

40-50. Similar to the iri-measure, the compounds given in