KR830005220A - Preparation of new 3- (1-piperidinylalkyl) -4H-pyrido [1,2-a] pyrimidin-4-wan derivatives - Google Patents

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Preparation of new 3- (1-piperidinylalkyl) -4H-pyrido [1,2-a] pyrimidin-4-wan derivatives

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Claims (11)

General Formula, A compound selected from the group consisting of 3- [1-piperidinyl) alkyl] -4H-pyrido [1,2-a] pyrimidin-4-wan derivatives represented by &lt; RTI ID = 0.0 &gt; and acid addition salts &lt; / RTI &gt; Wherein R ¹ and R ² are each independently selected from hydrogen, lower alkyl, lower alkyloxy, halo and trifluoromethyl; R ³ is a member selected from the group consisting of hydrogen, lower alkyl and aryl; Alk is a lower alkylene radical; R is a member selected from the group consisting of hydrogen, lower alkyl, hydroxy, lower alkyloxy and hydroxymethyl at the 2-, 3-4 or 4-position of the piperidine ring; X is A member selected from the group consisting of> C = NOH and> C = N-NH ₂ , wherein R _a is hydrogen or lower alkyl and q is an integer 2 or 3; And Ar is aryl, which aryl is a member selected from the group consisting of phenyl, substituted phenyl, thienyl, furanyl and pyridinyl, and the double substituted phenyl is halo, lower alkyl, lower alkyloxy, trifluoromethyl, nitro, Each having 1 to 3 substituents independently selected from the group consisting of amino and hydroxy. A compound according to claim 1, wherein R is hydrogen. R is hydrogen, X is> C = O,> C (O-lower alkyl) ₂ or A compound according to claim 1. A compound according to claim 1 wherein R is hydrogen, X is> C═O and Alk is a 1,2-ethanediyl radical. 3- [2- [4- (4-fluorobenzoyl) -1-piperidinyl] ethyl] -2-methyl-4H-pyrido [1,2-a] pyrimidin-4-wan and its agents Compounds selected from the group consisting of "acid addition salts" usable as: General Formula, A compound selected from the group consisting of 4H-pyrido [1,2-a] pyrimidine-4-wan derivatives represented by " acid addition salts " usable as medicaments thereof. among these : R ¹ and R ² are each independently selected from the group consisting of hydrogen, lower alkyl, lower alkyloxy, halo and trifluoromethyl; R ³ is a member selected from the group consisting of hydrogen, lower alkyl and aryl; Alk is a lower alkylene radical; R is a member selected from the group consisting of hydrogen, lower alkyl, hydroxy, lower alkyloxy, hydroxymethyl at the 2-, 3- or 4- position of the piperidine ring; And R ⁴ and R ⁵ are each independently selected from the group consisting of hydrogen, halo, lower alkyl, lower alkyloxy, trifluoromethyl, nitro, amino and hydroxy; The aforementioned aryl is a member selected from the group consisting of phenyl, substituted phenyl, thienyl, furanyl and pyridinyl, wherein substituted phenyl is halo, lower alkyl, lower alkyloxy, trifluoromethyl, nitro, amino and Each having 1 to 3 substituents independently selected from the group consisting of hydroxy. General Formula, A compound selected from the group consisting of 3-[(1-piperidinyl) alkyl] -4H-pyrido [1,2-a] -4-wan derivatives represented by " acid addition salts " Process for preparation, wherein R ¹ and R ² are each independently selected from the group consisting of hydrogen, lower alkyl, lower alkyloxy, halo and trirofluoromethyl; R ³ is a member selected from the group consisting of hydrogen, lower alkyl and aryl; Alk is a lower alkylene radical; R is a member selected from the group consisting of hydrogen, lower alkyl, hydroxy, lower alkyloxy and hydroxymethyl at the 2-, 3- or 4- position of the piperidine ring; X is A member selected from the group consisting of> C = NOH and> C = N-NH ₂ , wherein R _a is hydrogen or lower alkyl and q is an integer 2 or 3; And Ar is aryl, where aryl is a member selected from the group consisting of phenyl, substituted phenyl, thienyl, furanyl and pyridinyl, of which substituted phenyl is halo, lower alkyl, lower alkyloxy, trifluoromethyl, nitro, It has 1 to 3 substituents each independently selected from the group consisting of amino and hydroxy and is characterized by the following. a) general formula A compound represented by General formula Reaction with the compound represented by. W represents a reactive ester such as a halo or sulfonyloxy group, which is carried out with the addition of a suitable base in a suitable reaction-inert organic solvent and better at the reflux temperature of the reaction mixture; or b) general formula Of compounds General Formula, Cyclization with Compounds. R ¹ , R ² , R ³ , Alk, X, R and Ar of the double reactants (IV) and (V) are described above and L is lower alkyloxy, hydroxy, halo, amino, mono- or di (lower alkyl). A) leaving a suitable leaving group such as amino, wherein the cyclization reaction is carried out by stirring the reactants together in the presence of a suitable reaction-inert solvent, more preferably at an elevated temperature; or c) i) a general formula, Of the compounds of the general formula, By hydrolysis of a compound. Wherein R ¹ , R ² , R ³ , Alk and R are as previously defined and R ⁴ and R ⁵ are each independently from the group consisting of hydrogen, haloloweralkyl, loweralkyloxy, trifluoromethyl, nitro, amino and hydroxy Is selected; or c) ii) a general formula, A suitable reducing agent such as sodium borohydride or sodium cyanoborohydride of the compound of Preparation by Reduction of Compounds. In this case, when sodium borohydride is used as the reducing agent, the reaction is carried out in an alkaline aqueous medium, more preferably in a mixture with an aqueous organic solvent; or c) iii) Preparation by acylation of a compound of formula (I-b) using preferably lower alkanoic acid and halogenated acyl and anhydride derivatives thereof; or c) iv) a general formula, By reduction of the carbonyl group of the compound of formula (Ic), such as by clemensen reduction using zinc amalgam and hydrochloric acid or by Wolf-Kisner reduction using hydrazine and alkali in boiling polar solvents at elevated temperatures Produce; or c) v) X is> C (O-lower alkyl) or Wherein q is a compound of formula (I), wherein q is described above, which can be derived from the corresponding carbonyl compound by ketalizing the latter; or c) vi) A compound of formula (I) in which X represents a radical of the formula <C = NOH or a radical of the formula> C = N-NH ₂ , from the corresponding carbonyl compound, the latter being hydrogen chloride hydroxylamine or Can be induced by reacting with hydrogen hydrazine, respectively; or c) vii) general formula Of compounds, general formula Preparation of the compound by reaction with formaldehyde or derivative thereof. The hydroxymethylation reaction is carried out by stirring and heating the starting compound (I-g) in a suitable polar solvent in the presence of a suitable base. And, if desired, the preparation of "acid addition salts" which can be used as medicaments of the products of the process. 3- [2- [4- (4-fluorobenzoyl) -1-piperidinyl] ethyl-2-methyl-4H-pyrido [1,2-a] pyrimidin-4-wan and its pharmaceuticals 3- (2-Chloroethyl) -2-methyl-4H-pyrido [1,2-a] pyrimidine-4-wan (4-fluorophenyl) selected from the group consisting of available "acid addition salts" (4-piperidinyl) A process for preparing compounds wherein methane is characterized by reaction with hydrochloride and for preparing "acid addition salts" which can be used as medicaments thereof if desired. General Formula, A method for producing a compound selected from the group consisting of 4H-pyrido [1,2-a] pyrimidine-4-wan derivatives represented by " acid addition salts " usable as medicaments thereof. among these : R ¹ and R ² are each independently selected from the group consisting of hydrogen, lower alkyl, lower alkyloxy, halo and trifluoromethyl: R ³ is a member selected from the group consisting of hydrogen, lower alkyl and aryl; Alk is a lower alkylene radical; R is a member selected from the group consisting of hydrogen, lower alkyl, hydroxy, lower alkyloxy, hydroxy methyl at the 2-, 3- or 4- position of the piperidine ring. And R ⁴ and R ⁵ are each independently selected from the group consisting of hydrogen, halo, lower alkyl, lower alkyloxy, trifluoromethyl, nitro, amino and hydroxy; Aryl is a member selected from the group consisting of phenyl, substituted phenyl, thienyl, furanyl and pyridinyl, said substituted phenyl being halo, lower alkyl, lower alkyloxy, trifluoromethyl, nitro, amino and hydroxy Each having 1 to 3 substituents independently selected from the group consisting of In addition, the compound is a general formula, General formula of a compound of Characterized by reaction with a compound of, wherein W is represented by a reactive ester group such as halo or sulfonyloxy group, the reaction being carried out by addition of a suitable base in a suitable reaction-inert organic solvent, the reaction of the reaction mixture It performs better at reflux temperature. And, if desired, a process for preparing acid addition salts which can be used as a medicament of this product. Use of a compound of formula (I) as a seratonin-antagonist. A seratonin-antagonist containing a compound of formula (I) as a carrier usable as an active ingredient and a medicament. ※ Note: The disclosure is based on the initial application.