SU999974A3 - Process for producing condensed derivatives of pyrimidine or their salts - Google Patents

Abstract

Compounds of the general formula <IMAGE> [wherein R and R<1> are H or C1-4alkyl, or together form (CH=CH)-2, R<2> is H or C1-4alkyl R<3> is H, C1-4alkyl, phenyl, carboxy or salt thereof, alkoxycarbonyl, carbamoyl, cyano, -CO-NH-CO-SO2-C6H4-p-CH3 or -(CH2)s-COOR<14> (s is 1, 2 or 3 and R<14> is H or C1-4alkyl, n is 0 or 1, (a) if R<13> is H, and R<12->R<11> and R<9->R<10> form bonds then YR<7>R<8> represents oxygen or sulfur, or Y represents nitrogen, R<7> is C1-4alkyl, optionally substituted C6-10aryl or C7-12aralkyl, R<8> is a lone pair of electrons or C1-4 alkyl and in this latter case a salt is formed; and XR<4>R<5>R<6> represents halogen; or XR<5>R<6> represents oxygen or sulfur, and R<4> is H or C1-4alkyl, XR<6> represents nitrogen and R<4> is chloroacetyl, C1-4alkyl or optionally substituted C6-10aryl or heteroaryl and R<5> is H or alkyl or (b) if R<11> is H and R<9->R<10> and R<12->R<13> form bonds, then R<4>, R<5>, R<6>, R<7>, R<8>, X and Y are as defined in item (a) and (c) if R<10->R<11> and R<12->R<13> form bonds, then YR<7>R<8>R<9> represents an oxygen or sulfur anion or YR<8>R<9> represents oxygen or sulphur and R<7> is H or C1-4alkyl; or YR<9> represents nitrogen, R<7> is H, C1-4alkyl or optionally substituted C6-10aryl, and R<8> is C1-4alkyl, and XR<4>R<5>R<6> represents halogen or an oxygen or sulfur anion or XR<5>R<6> is O or S and R<4> is H or C1-4alkyl, or XR<6> represents nitrogen, R<4> is chloroacetyl, C1-4alkyl or optionally substituted C6-10aryl or heteroaryl and R<5> is H or C1-4alkyl, and if YR<8>R<9> and XR<5>R<6> each represent oxygen or or sulfur or if YR<9> and XR<6> each represent nitrogen (R<5> and R<8> each being H or C1-4alkyl), then R<4> and R<7> together form optionally substituted -(CH2)-s (s is 1, 2, 3 or 4)] and the tautomers and salts thereof. The compounds have physiological activity.

Description

or their salts, which means that the compound of the general formula where R, R and p have the indicated meanings, is reacted with carbon disulfide in the presence of alkali metal cations, in a lower alcohol medium, at room temperature, followed by isolation of the Target Product or by subsequent reaction compounds with ethylene dihalogenide, ethylene diamine or an alkylating reagent and the target products are isolated in free form or in the form of salts. Example. 5.9 g of 3-ethoxycaro-a56nyl-6-methyl-4-bxo-b, 7,8, 9-tetra1Hydro-4H-pyrido- (1, 2-a) -pyrimidine and 2.3 ml of carbon disulfide are dissolved in J5 ml of ethanol and 2.8 g of potassium hydroxide in 25 ml of ethanol are added dropwise to it at 25-30 ° C. The reaction mixture is stirred for 1 hour at room temperature and evaporated under reduced pressure. 9.8 g of 3-ethoxy-carbonyl-b-methyl-9- (bis-thiolate) -methylene-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyridine are obtained in the form of two-potassium salt. Primv p 2. To a solution of 9.7 g of 3ethoxycarbonyl-b-methyl-9-C (methylene bis-thiolate} -4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine in the form of a two-; potassium salt prepared according to the method of example 1 in 60 ml (danol is bavlutt dropwise with external cooling of 4.7 ml of dimethyl sulfate and the reaction mixture is stirred for 1 part. The yellow crystals separated out are washed with 45, washed with water and dried. Obtain 7.1 g (86%) of 3 is sicarbonyl-b-methyl-9- (methylthio-thiocarbonyl) -4-OXO-1,6,7,8-tetrahydro-4H-pyrido {1, 2-a) -pyrimidine. After distillation from benzene, produce / is set at 198-199 ° C. Elemental analysis for C g Calculated,%: C 51.51; n 5.56; N 8.58. Found,%: C 51.70; H 5.78; N 8.48 Example 3. To a solution of 9.7 g of 3-ethoxycarbonyl-6-methyl-9- (bis thiolate) methylene-4-oxo-6,7,8,9-tet rahydro-4n-pyrido (1,2- a) pyrimidine in the form of a two-potassium salt prepared according to the procedure of Example 1, 4.7 g of ethylene bromide was added to 60 ml of ethanol.The reaction mixture was stirred for 1 hour at and the sodium bromide was filtered off. The mother liquor is evaporated by half, the crystals separated out after cooling are filtered and dried. 3 g of 3-ethoxycarbonyl-6-methyl-9- (1,3-dithiolan-2-ylidene) -4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine are obtained - which, after recrystallization from ethanol, melts at 205-207 0. Elemental analysis for (. Calculated,%: C, 53.28; H, 5.36; N- 8.27. Found,%: 53.17; H 5.41; N 8.22. Example 4. 3.26 g of 3-ethoxycarbonyl-6-methyl-9- (methylthio-thiocarbonyl) -4-OXO-1, b, 7,8-tetrahydro-4H-pyrido ( 1/2-a) of pyrimidine in 20 ml of acetic anhydride is boiled for 2 hours. After cooling, the separated crystals are filtered, washed with benzene, and dried to give 1.6 g (57.6%) of 3-ethoxycarbonyl-6-methyl- 9-4- {3- ethoxycarbonyl-6-methyl-1, 3-dithiolan-2-ylidene-4-oxo-b, 7,8,9 tetrahydro-4H-pyrido (1,2-a) pyrimidine, which, after crystallization from dimethylformamide, melts at 315318 ° C. , ./ Elemental analysis for C bN 1 4-b 2 Calculated,%: C 56.10; H 5.07; N 10.07; S 10.52; Found,%: C 55.89; - H 4, 91; N 10.20; S lOfSO. Example 5, 3.26 g of 3-ethoxycarbonyl-6-methyl-9- (methylthio-thiocarbonyl) -4-OXO-1, 6,7,8-tetrahydro-4H-. , -pyrido (1,2-a) pyrimidine and 0.6 g ethylene diamine in 50 ml of benzene are boiled for 10 hours. After cooling, the separated yellow crystals are filtered, covered with benzene and dried. 1.9 g (62%) of 3-ethoxycarbonyl-6-meter-9- {2-imidazolidin) -4-oxo-6 are obtained, 7,8,9-tetrahydro-4H-pyrido {1,2-a) pyrimidine which, after recrystallization from dimethylformamide, melts at 252-254 ° C. Elemental, dl. Oy analysis. Calculated,%: C 59.15; H 5.90; N 18.40. Found,%: C 58.91; H 5.85; N 18.35. Example To a solution of 0.8 g of 3-cyano-4-oxo-4,6,7,8-tetrahydro-pyrrolo- (1,2-a) pyrimidine and 0.6 ml of carbon disulfide in 10 ml of ethanol is added dropwise a solution 0.6 g of potassium hydroxide in 10 ml of ethanol. The reaction mixture is stirred at room temperature for 1 h and evaporated under reduced pressure. A two-potassium salt of Z-cyano-9- (bis-thiolate) -methylene-4-oxo-4, 6,7,8-tetrahydropyrrolo (1,2-a) pyrimidine is obtained. EXAMPLE 7 Cyano-9- (bis-thiolate) methylene-4-oxo-4, 6,7,8-tetrahydro-pyrrolo (1,2-a) pi two-potassium salt

Claims (1)

Claim The method of obtaining condensed pyrimidine derivatives of the General formula <·>. t -pyrido (1,2-a) pyrimidine and 0.6 g of ethi; 20 ® case, lendiamine is dripped for 10 hours in 50 ml of benzene. After cooling, the yellow crystals precipitated are filtered off, squeezed with benzene and dried. 1.9 g (69% of theory) of 25-carbonyl-b-methyl-9- (2-imidazolidene) -4-oxo-b, 7.8.9-tetrahydro-4H-pyrido (1.2) are obtained. -a) pyrimidine, which after recrystallization from dimethylformamide melts at 252-254 ^ 0. Elemental analysis for Calculated,%: С 59., 1'5 *; ~ Н 5.9и; 18.40. 58.91; H 5.85; 18.35. where R is a hydrogen atom or Cj-Cj-alkyl; R is alkoxycarbonyl with 2-5 carbon atoms or a cyano group; η = 0 or 1, _Ί a) in the case when R is a hydrogen atom, 'R ^ HR ⁶ , as well as R' and R ⁴ are an .. additional bond, x and y are sulfur, R ² is C ^ -alkyl, or when R ⁶ h R ⁷ as well R ⁴ and R ⁵ are an additional bond, x and y are negatively charged sulfur atoms, and R ² and R® are an alkali metal cation, or; x and y are sulfur atoms or a group of the formula> Ν - Η, ^Λ ”but are a group of the formula. - (CH ^) ^ or them. salts, characterized in that the compound of the general formula a R ¹ and R ^{5 are} compatible30 N Found,%: C N ι '· 4 · Dissolve 1.0 g of 3-ethoxycarbonyl-b-methyl-9- (2-imidazolylene) -4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine in 10 ml of ethanol . The solution was saturated with gaseous hydrogen chloride and evaporated. The residue was recrystallized from a mixture of ether and ethanol. 0.9 g of 3-ethoxycarbonyl-6- 45-methyl-9- (2-imidaeoliden) -4-oxo-b, 7.8,9-tetrahydro-4H-pyrido (.1,2-a) is obtained ) pyrimidine, which melts with decomposition. 59.15, 18.40. 58.91; H 5.85; 18.35. eat at 190 “s. Elemental Calculated Found,%: analysis for FROM N FROM N%: