Category: 485-71-2

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.485-71-2,Cinchonidine,as a common compound, the synthetic route is as follows.,485-71-2

General procedure: The alkaloid (12.3 mmol, 1 eq.) and the appropriate substituted benzylic halide derivative(12.3 mmol, 1 eq.) were dissolved in THF (40 mL) with addition of a trace of NaI. The mixture washeated to reflux overnight and then cooled and stirred at ambient temperature for 1 h. In most cases theproduct precipitated as an off-white solid, but where this was not the case and the mixture containedonly a small amount of solid or no solid at all, then diethyl ether (20 mL) was added dropwise.The solid was removed via filtration and washed with THF (50 mL) or ether:THF, (1:1, v/v, 50 mL)and was dried under reduced pressure at 40 C. Where the solid formed was not a fine powder it was then taken up in DCM and this solution was then added dropwise to rapidly stirring ether (100 mL).This usually gives a finely divided solid that could be filtered and dried. (Note: The cinchonine derivedPTCs are usually very insoluble. The quinidine derived PTCs are often completely soluble at the endof the reaction.) The di(t-butyl)benzyl PTC was prepared according to the standard procedure aboveand was filtered directly from the reaction mixture.

485-71-2 Cinchonidine 101744, acatalyst-ligand compound, is more and more widely used in various.

Reference£º
Article; Zhang, Tao; Scalabrino, Gaia; Frankish, Neil; Sheridan, Helen; Molecules; vol. 23; 7; (2018);,
Metal catalyst and ligand design
Ligand Template Strategies for Catalyst Encapsulation – NCBI

485-71-2, Cinchonidine is a catalyst-ligand compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,485-71-2

Resolution of the enantiomers of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylic acid The resolution of the enantiomers of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylic acid was carried out via reaction with the following chiral bases: BrucineQuinine(-)-Cinchonidine(+)-CinchonineR-(+)-1-Phenylethylamine(1 R,2S)-(-)-Ephedrine hydrochloride(1S,2R)-(+)-Ephedrine hydrochloride. In each case the reactions were carried out with 0.5 and 1 equivalents of base in respect to 1 equivalent of the acid compound and by using the following solvents EthanolAcetoneAcetonitrilDioxaneEthylacetateChloroform. The results are summarized in the following tables. It may be understood that the afore mentioned crystallisation experiments that are not reflected in the following tables did not yield crystals of the respective salts under the given conditions. However, suitable conditions for crystallization of these salts can be determined by those skilled in the art via routine experiments. In the following tables Acid represents racemic 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazo)e-3-carboxylic acid R-Acid represents the respective derivative of (R)-5-( 4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylic acid S-Acid represents the respective derivative of (S)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-pyrazole-3-carboxylic acidProcesses for crystallisation: Process A: A solution of the chiral base was added on top of a solution of the racemic acid at room temperature.Process C: A solution of the racemic acid was added on top of a solution of the chiral base. The mixture was heated to reflux and solvent was added until dissolution was complete. The solution was left to crystallisation at r.t.Process D: The chiral base was directly added on top of a solution of the racemic acid at room temperature.Process E: The chiral base was directly added on top of a solution of the racemic acid at reflux temperature.Process F: The solution of the salt was evaporated to dryness. The residue was dissolved in a minimum amount of the solvent under reflux heating. The solution was left to crystallisation at r.t.Resolution with (-)-Cinchonidine [Show Image] Acid g (mmol) Eq. amine Proc. Solvent for crystallisation T CrystYield 1st Cryst. % % S-Acid % R-Acid0,4 g (1,09 mmol) 1 F 2ml dioxane r.t 31 94,4 5,60,4 g (1,09 mmol) 1 F 19ml Ethylacetate r.t 28,5 95,8 4,20,4 g (1,09 mmol) 1 F 20ml acetone r.t. 19,6 96,9 3,10,4 g (1,09 mmol) 1 F 24ml acetonitrile r.t 42 85,8 14,1

As the paragraph descriping shows that 485-71-2 is playing an increasingly important role.

Reference£º
Patent; Laboratorios del Dr. Esteve S.A.; EP1944293; (2008); A1;,
Metal catalyst and ligand design
Ligand Template Strategies for Catalyst Encapsulation – NCBI

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.485-71-2,Cinchonidine,as a common compound, the synthetic route is as follows.,485-71-2

General procedure: A mixture of 2 or 3 (0.50 mmol), the corresponding acids RCOOH (0.60 mmol),DCC (0.60 mmol), DMAP (0.1 mmol) in dry dichloromethane (15 mL) was stirred atroom temperature. When the reaction was completed, and checked by TLC, the mixturewas filtered to remove urea from the reaction, and the filtrate was diluted bydichloromethane (45 mL). Subsequently, the diluted organic phase was washed bysaturated aqueous NaHCO3 (30 mL), and brine (30 mL), dried over anhydrousNa2SO4, concentrated in vacuo, and purified by CC to give the pure 9R/S-acyloxyderivatives of cinchonidine and cinchonine 5a-j,l-o and 6a,c,e-o [17-19]. The dataof target compounds are shown as follows.

The synthetic route of 485-71-2 has been constantly updated, and we look forward to future research findings.

Reference£º
Article; Che, Zhi-Ping; Chen, Gen-Qiang; Jiang, Jia; Lin, Xiao-Min; Liu, Sheng-Ming; Sun, Di; Tian, Yue-E; Yang, Jin-Ming; Zhang, Song; Journal of Asian Natural Products Research; (2020);,
Metal catalyst and ligand design
Ligand Template Strategies for Catalyst Encapsulation – NCBI

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.485-71-2,Cinchonidine,as a common compound, the synthetic route is as follows.

Preparation method of this embodiment Example 1 is the preparation method of compound 3a, which specifically includes the following steps: 0.5 mmol of cinconidine(1), 0.6 mmol of acetic acid (2a), 0.6 mmol of DCC, and 0.1 mmol of DMAP In a 50mL flask, then add dichloromethane (10mL) dried with calcium hydride, and then react at room temperature. The reaction process was followed by TLC to detect that the raw material (cinconidine) was complete. The reaction was completed. Urea gives the filtrate. The filtrate was then diluted with 50 mL of dichloromethane to obtain a dilution solution. The dilution solution was washed with 30 mL of 0.1 mol / L hydrochloric acid, 30 mL of a saturated sodium bicarbonate solution, and 30 mL of a saturated saline solution successively, and then dried over anhydrous sodium sulfate. . Then, the solvent (dichloromethane) was removed from the dried diluent under reduced pressure, and then separated by silica gel column chromatography (eluent was a mixed solution of ethyl acetate and petroleum ether with a volume ratio of 1: 1) to obtain compound 3a. The yield is 39%.

485-71-2 Cinchonidine 101744, acatalyst-ligand compound, is more and more widely used in various.

Reference£º
Patent; Henan University of Science and Technology; Che Zhiping; Tian Yuee; Chen Genqiang; Liu Shengming; Lin Xiaomin; Jiang Jia; Sun Di; Yang Jinming; (22 pag.)CN110642855; (2020); A;,
Metal catalyst and ligand design
Ligand Template Strategies for Catalyst Encapsulation – NCBI

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.485-71-2,Cinchonidine,as a common compound, the synthetic route is as follows.

General procedure: A mixture of (-)-cinchonidine (1.0 mmol) and benzyl bromide 3 (1.0 mmol) having sulfonamidegroup was stirred in DMF (4 mL) at 25 C for 20 h. After the reaction was completed, the reaction mixture was added dropwise to ether (50mL) with stirring. The solid precipitated was filtered,washed with ether (20 mL) and hexane (20 mL) to afford cinchonidinium salt 5

As the paragraph descriping shows that 485-71-2 is playing an increasingly important role.

Reference£º
Article; Itsuno, Shinichi; Yamamoto, Shunya; Takata, Shohei; Tetrahedron Letters; vol. 55; 44; (2014); p. 6117 – 6120;,
Metal catalyst and ligand design
Ligand Template Strategies for Catalyst Encapsulation – NCBI

485-71-2, Cinchonidine is a catalyst-ligand compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Previous resolution of CPTA has been reported in U. S. Patent No. 3,517, 050, in which cinchonidine was used as the chiral base, and the (+)-enantiomer of CPTA precipitated as the diastereomeric salt. One major drawback to this procedure was that the desired (-)- enantiomer remained in the mother liquor, making separation of a pure (-)-enantiomer fraction difficult. [0092] This example shows the results of resolving a racemic mixture of CPTA using A variety of different chiral bases to obtain a solid enantiomerically enriched (-) -isomer. Unlike the previous method, methods of the present invention allow the solid enantiomerically enriched (-) -CPTA to be readily isolated from the solution. [0093] Racemic CPTA was prepared by the potassium hydroxide hydrolysis of racemic halofenate. For chiral base screening, equal molar mixtures of CPTA and the chiral base were mixed in ethanol, methanol and acetone in glass vials, and the solutions were allowed to stand undisturbed. After holding overnight at ambient temperature, the samples that remained in solution were placed in a refrigerator at 5 C. After holding overnight in the refrigerator, a small amount of water was added to the samples that remained a solution in ethanol. After four days at ambient temperature, the aqueous ethanol solutions were placed back in the refrigerator. All of the samples remained in the refrigerator, and were periodically checked for precipitate formation over the course of a month. A list of the bases and solvent conditions examined, and temperatures at which crystalline salts were found is shown in Table 1. Table 1. Bases Examined for CPTA Resolution. Solvent System Base EtOH EtOH (aq) Acetone MeOH S- (-)-Methylbenzylamine E E E E Quinine C (22 C) C (22 C) C (22 C) Quinidine E E L-Tyrosine Hydrazide C (22 C) L-Leucine Methyl Ester Hydrochloride* E E 1-2-Amino-l-butanol E E E E Brucine E E E E (S)-(+)-2-Pyrrolidine-methanol E E E E (S)-(+)-2-Amino-3-methyl-1-butanol E (S)- (+)-2-Amino-1-propanol E (S)-(-)-2-Amino-3-phenyl-1-propanol E (1 S, 2S)-(+)-Pseudoephedrine E E E E (1S,2S)-(+)-2-Amino-1-phenyl-1,3-propanediol E E E E (1 S, 2S)-(+)-2-Amino-1-(4-nitrophenyl)-1, 3-propandiol C (5 C) (lR, 2S)- (-)-Norephedrine E E E E (1R,2R)-(-)-Ephedrine (1R,2R)-(-)-2-Amino-1-(4-nitrophenyl)-1, 3-propandiol C (22 C) (+)-Cinchonone E E E E (-)-Cinchonidine C (22 C) (-)-Strychnine E E E E E-Evaluated C-Crystallized at (Temperature) *-With 1 MOL/MOL of Aqueous Sodium Hydroxide [0094] Four chiral bases, quinine, L-tyrosine hydrazide, (-) -cinchonidine, and both enantiomers of 2-amino-1-(4-nitrophenyl)-1, 3-propandiol, were found to give crystalline salts from racemic CPTA. For samples that crystallized, the solid was isolated by filtration, and both the solid phase and mother liquor were analyzed by chiral HPLC to determine the enantiomeric composition of both streams. The results from the screen are shown in Table 2. Three of the bases shown in Table 2 gave the (+) -enantiomer enrichment in the solid phase. Table 2. Results from Chiral Base Screen. Solid Mother Liquor % Yield Base % (+) % (-) % (+) % (-) Calculated Solvent Temp C L-Tyrosine Hydrazide Acetone 22 86. 6 13. 4 40. 7 59.3 20.3 (-) -Cinchonidine Ethanol 22 66.8 33.2 12. 0 88.0 69.3 (1S, 2S)- (+)-2-Amino-1- (4- Ethanol 22 93. 2 6.8 28.5 71. 5 33. 2 nitrophenyl)-1, 3-propandiol Quinine Ethanol 22 39.9 60.1 60.1 39.9 50.1 Acetone 22 28. 2 71.8 58.9 41. 1 28. 9 Acetone* 5 23. 0 77.0 83. 5 16. 5 55. 4 Methanol 22 25. 8 74.2 53.0 47. 0 10. 9 2-Propanol 30 43. 2 56.8 64.3 35. 7 67. 6 2-Propanol** 30 40. 4 59.6 78.8 21. 1 75. 0 2-Propanol* 21 42.3 57.7 59.1 40.9 53.9 *-More Dilute **-Slower Cooling Profile [0095] Included in Table 2 is the percent yield of solid calculated from the isomeric ratio in the solid and mother liquor streams. The equation used is shown below. The maximum theoretical yield with 100% isomeric purity is 50%. Yields over 50% indicate inclusion of the other isomer. Equation to calculate yield from isomer ratios. Set: a = area % Component 1 in starting material; b = area % Component 2 in starting material; x = area % Component 1 in isolated; y = area % Component 2 in isolated; w = area % Component 1 in mother liquor; z = area % Component 2 in mother liquor; E = g material isolated; F = g material in mother liquor. And: A+B=100% ; E+F=L Then: XE+WF=A ; YE+ZF=B Solving: XE + W (1-E) = A ; YE + Z (1-E) = B E = isolated yield = (A-W)/ (X-W) = (B-Z)/ (Y-Z)This example shows representative results of chiral resolution screening in ethanol using a variety of chiral bases. [0113] A sample of 1.16 g (3.51 mmol) of CPTA was dissolved in 6.98 g of ethanol to give a solution (0.431 mmol/g). Glass vials were individually charged with the amounts of each base listed in Table 5, and the amount of the ethanolic CPTA solution calculated to give a 1 to 1 molar ratio of acid to base was added. In some cases, a small amount of ethanol was added to wet the base prior to addition of the CPTA solut…

As the paragraph descriping shows that 485-71-2 is playing an increasingly important role.

Reference£º
Patent; METABOLEX, INC.; WO2004/112774; (2004); A1;,
Metal catalyst and ligand design
Ligand Template Strategies for Catalyst Encapsulation – NCBI