50451-22-4

Upstream product

• 109-01-3 1-methyl-piperazine 
• 506-68-3 bromocyane 
• 66443-73-0 N-allyl-4-methylpiperazine 

Relevant academic research and scientific papers

Benzoxazinone derivatives and their use as antibacterial agents

The invention discloses benzoxazinone derivatives, a synthesis method and applications thereof. The derivatives can be used as an antibacterial agent for treating infectious diseases caused by bacteria, especially tuberculosis (TB) caused by mycobacterium. Specifically, the invention relates to compounds represented by the formula (I), pharmaceutically acceptable salts thereof, and a pharmaceutical composition comprising the provided compounds; wherein the R1 to R4 are defined in the description. The invention aim to prepare novel compounds capable of inhibiting the mycobacterium activity, the compounds can be used as a potential novel drug for treating infectious diseases caused by bacteria, moreover, the compounds can be used to treat or prevent tuberculosis (TB) caused by mycobacterium, at the same time the problems related with drug resistance can be solved, and the drug metabolism property can be improved on the basis that the mycobacterium tuberculosis resistant activity is not influenced.

A allyl uncle amine compound by one-step synthesis method of cyano uncle amine compound (by machine translation)

The invention relates to a one-step synthesis of amine compound allyl unclecyano uncle amine compounds, which belongs to the technical field of organic synthetic method. The method specific synthetic process is as follows: in the airtight reaction environment, to the anhydrous organic solvent is added in the cyanogen bromide, under protection of inert gas, and then added dropwise to the solution in the allylic and high yield amine compound, to obtain allyl uncle amine compound concentration is 0.8 - 1 mol/L solution, at room temperature the reaction 16 - 24 hours later, after column chromatography separation and purification, to obtain a corresponding cyano uncle amine compound. The method to get rid of the expensive deallylation use of the catalyst, the synthesis step is less, raw materials are easy, cheap, mild reaction conditions, the operation is simple, easy to craft and industrialization. Yield 50% - 80% between. (by machine translation)

Synthesis of Cyanamides from Cyanogen Bromide under Mild Conditions through N-Cyanation of Allylic Tertiary Amines

Cyanamides were selectively formed through a one-step nucleophilic substitution reaction of allylic tertiary amines with cyanogen bromide. Because of the mild reaction conditions and good yields of the reaction, as well as the commercial availability of the starting materials, this new method represents a valuable tool for the synthesis of cyan-amides through an N-deallylation reaction and an N-cyanation reaction in one pot.

3,5-Disubstituted-[1,2,4]-oxadiazoles and analogs as activators of caspases and inducers of apoptosis and the use thereof

Disclosed are 3,5-disubstituted-[1,2,4]-oxadiazoles and analogs thereof, represented by the Formula I: wherein Ar1, R2, A, B and D are defined herein. The present invention relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

Synthesis and anti-arrhythmic activity of aminoguanidine derivatives

A series of new aminoguanidine derivatives were synthesized and tested for anti-arrhythmic activity.The compounds selected were investigated on other test models.Finally, compound 13 1-(2,6-dimethylphenyl)-4,4-dimethyl-aminoguanidine-hydrochloride (B-GYKI-38 233) was chosen for detailed study. aminoguanidines / anti-arrhythmic activity

Process for preparing 3-(cyanimino)-3-amino-propionitriles

An improved multistep process for the production of intermediates for hypotensive compounds, which intermediates are of the formula V: STR1 wherein R1 and R2 are lower alkyl of 1 to 4 carbon atoms, inclusive, alkenyl of 3 or 4 carbon atoms, cycloalkyl from 3 to 7 carbon atoms, phenylalkyl in which the alkyl group is defined as above, or the group STR2 is a heterocyclic moiety of 4 to 8 ring members, e.g., azetidinyl, piperidino, pyrrolidinyl, hexahydroazepinyl, or heptamethyleneimino, each of which can be substituted by one or two methyl groups, N-alkylpiperazino, wherein alkyl is defined as above, morpholino, or thiomorpholino, and wherein R3 is hydrogen or alkyl of 1 to 4 carbon atoms, inclusive, starts with the corresponding secondary amine I STR3 wherein R1 and R2 have the significance of above. SU BRIEF SUMMARY OF THE INVENTION This invention is concerned with a new, improved process for the production of 2,N-dicyanoacetamidines which are the primary intermediates for anti-hypertensive 2,4-diamino-6-aminopyrimidine-3-oxides. This process can be illustratively represented as follows: STR4 wherein R1 and R2 are alkyl of 1 to 4 carbon atoms, inclusive, alkenyl of 3 to 4 carbon atoms inclusive, cycloalkyl from 3 to 7 carbon atoms, inclusive, phenylalkyl in which the alkyl group is defined as above, or the group STR5 is a heterocyclic moiety of 4 to 8 ring members, e.g., azetidinyl, pyrrolidinyl, piperidino, hexahydroazepinyl, or heptamethyleneimino, each of which can be substituted by 1 to 2 methyl groups, or 4-morpholino, 4-thiomorpholino, or N-alkylpiperazino, in which alkyl is defined as above; wherein R3 is hydrogen or alkyl defined as above, wherein X is chlorine, bromine or iodine. M is a metal ion selected from the group consisting of lithium, sodium, potassium, magnesium, calcium or aluminum, and Alk is alkyl of 1 to 4 carbon atoms, inclusive. From compounds of formula V, the final desired compounds VI are prepared by the single step: STR6 See U.S. Pat. No. 3,910,928. FIELD OF THE INVENTION The principal compound in this field is the compound in which STR7 is piperidino; thus the intermediate has the formula Va (below), and the final product has the formula VIa (below), produced by the process STR8 Prior to the present invention, compound Va has been produced by the following process: STR9 In the present new process the intermediate Va is produced by the following specific synthesis: STR10 The advantages in this process are: (1) the cost of the new process is less, since the price of cyanoacetic acid is only about one-third of that of malononitrile; (2) the new process provides 20-25% relative yield increase with a lower cost. In the new four-step synthesis of this invention, the step IV to V is similar to the reaction described in J. Chem. Soc. Chemical Communication, page 350, 1974, by Kristinsson. However, Kristinsson used cyanoacetic acid ethyl ester rather than the free acid, and as a result the carbethoxy group was incorporated into a new ring (a uracil ring). Thus, the process of Kristinsson cannot be used in this synthesis to give compounds of structure V, and therefore the last step is novel. DETAILED DESCRIPTION The preferred process of this invention is that in which the starting compounds are heterocyclic secondary amines, such as pyrrolidine, piperidine, morpholine, thiomorpholine, hexahydroazepine, heptamethyleneimine or N-alkylpiperazine in which alkyl is of 1 to 4 carbon atoms, inclusive. Most preferred of these starting compounds is piperidine, of which the process (with starting compound Ia) has been described above. The process with starting compound Ia provides the compound Va. Compound Va is the last intermediate used to make compound VIa: STR11 Compound VIa, under the generic name, minoxidil, is one of the more effective drugs in the treatment of hypertension, and works particularly well in the treatment of patients having toxic hypertension, often intractable by other drugs, and the patients are therefore in acute danger of life. Minoxidil is still a clinical experimental drug. Other compounds of formula VI also have been found to be anti-hypertensives and are useful for the treatment of hypertensive patients. U.S. Pat. No. 3,461,461 provides the details of how to use the compounds of formula VI in oral and parenteral formulations and the dosages and modes of administration. The new process for the final intermediates of formula V, herein claimed, is useful to lower the price of the final medicament of formula VI. In carrying out the process of the invention, a selected secondary amine of formula I is reacted in solution with cyanogen halide and a base. Solvents used in this reaction include water, ether and non-polar organic solvents, such as diethyl or dipropyl ether, methylethyl ether, tetrahydrofuran, ethyl acetate, acetone and hydrocarbons, e.g., pentane, hexane, toluene and the like. The reaction temperature is preferably kept low, between about 0° and 15° C. when water is solvent, and can be lower for the organic solvents. A two-phase system, water-organic solvent, is preferred. As bases, sodium or potassium hydroxide or carbonate are preferred, usually in aqueous solution. In the preferred embodiment of this invention a solution of the secondary amine is cooled to 0° to 10° C. and cyanogen halide is slowly added, in small portions, using an excess of 10% to 25%. Larger excess of this reagent is operative, but is not necessary or desirable. The base, aqueous sodium or potassium hydroxide is preferred, is added slowly and the temperature is kept at the low level of 0° to 10° C. After stirring for 1/2 to 2 hours, the product II, the carbonitrile of the amine, is isolated and purified by conventional procedures, such as extraction, washing, chromatography, crystallization, distillation and the like. Cyanogen halide used in this process is available commercially or can be made by standard methods, e.g., using sodium cyanide and a halogen source. Compound II is treated with a metal alkoxide of which the alkyl group of the alkoxide is of 1 to 4 carbon atoms, inclusive, and the metal is lithium, sodium, potassium, magnesium or aluminum, in a lower alkanol solution of 1 to 4 carbon atoms, inclusive, to give compound III. Sodium or potassium methoxide or ethoxide is preferred. In the preferred embodiment of the invention the N-carbonitrile of the amine (II) in methanol is reacted at 10° to 50° C. preferably at room temperature (20° to 30° C.) with the methoxide. Higher or lower temperatures can be selected and are operative in this reaction. The reaction time is from 2 to 48 hours. At the termination of the reaction the resultant compound, a methyl 1-aminocarboximidate (III), is isolated and purified by conventional means, e.g., extraction, evaporation, crystallization, distillation or the like. Compound III in solution is treated with a cyanogen halide and thereto is added a base to produce compound IV. As solvent, ethers, e.g., methylethyl, diethyl, ethylpropyl ether or tetrahydrofuran, or hydrocarbons, e.g., hexane or toluene, or mixtures thereof, or the like may be used. As base sodium or potassium carbonate or bicarbonate is utilized. In the preferred embodiment of this invention to a solution of compound III in an ether is added cyanogen bromide followed by anhydrous sodium or potassium carbonate. The reaction is carried out between 0° C. and the boiling temperature of the solvent, with room temperature preferred. The reaction time is between 2 to 48 hours. After the reaction is terminated, the product IV, a methyl N'-cyano-1-carboximidate, is isolated and purified by conventional means, e.g., filtration, evaporation, extraction, chromatography, crystallization or the like. Compound IV is converted to compound V, a 2,N-dicyanoacetamidine, by treating a solution of IV with a solution of a cyanoacetic acid of formula X, and a base. Preferred bases are sodium or potassium alkoxides. As solvents alcohols, e.g., methanol, ethanol and the like, ethers, e.g., tetrahydrofuran, diethylether, hydrocarbons, e.g., benzene, toluene and the like, dimethylformamide, or mixtures thereof, or the like can be used. The solution of the cyanoacetic acid VII and base is mixed with a solution of compound IV in one of the before-mentioned solvents. The mixture is stirred from 1 to 48 hours at temperatures between 0° and 50° C. with room temperature (20° to 30° C.) preferred. After the reaction is terminated, the solution is acidified, preferably with acetic acid, evaporated and extracted. The product is isolated from the extracts and purified in conventional manners, e.g., by extraction, crystallization, chromatography, distillation or the like. Starting cyanoacetic acids if not commercially available can be synthesized by the method cited by R. B. Wagner et al. in "Synthetic Organic Chemistry", John Wiley (1965) p. 593.