Month: November 2020

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps,and cheap raw materials. 1193-24-4, name is 4,6-Dihydroxypyrimidine. A new synthetic method of this compound is introduced below., 1193-24-4

EXAMPLE 12 4,6-Dihydroxypyrimidine (0.5 g, 4.46 mmol) was suspended in chlorobenzene (10 ml) and dichlorotriphenylphosphorane (1.44 g, 4.46 mmol; previously prepared by the reaction of triphenylphosphine oxide with phosgene) was added as a solid. The mixture was stirred at 80 C. to 90 C. under a nitrogen atmosphere. Analysis by thin layer chromatography (tlc) of a sample removed after 90 minutes showed some 4,6-dichloropyrimidine formation. However, quite a lot of 4,6-dihydroxypyrimidine remained out of solution. Another quantity of dichlorotriphenylphosphorane (1.44 g, 4.46 mmol) was added and stirring continued for a further hour at 110 C. A cloudy yellow solution was obtained with a solid residue. Analysis by tlc confirmed the formation of 4,6-dichloropyrimidine.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,1193-24-4, 4,6-Dihydroxypyrimidine, and friends who are interested can also refer to it.

Reference:
Patent; Zeneca Limited; US6160117; (2000); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The major producers of chemicals have been the Europe, Japan and China. Due to the growing call for a cleaner, greener environment, people will have to find innovative ways to maintain their relevance. Here is a compound 4595-59-9, name is 5-Bromopyrimidine. This compound has unique chemical properties. The synthetic route is as follows. 4595-59-9

General procedure: To the catalyst (1.0 mol%) dissolved in 1 ml DMAc, aryl bromide (1.0 mmol), phenyl boronic acid (1.5 mmol) in 1 ml ethanol, K2CO3 (2.0 mmol) in 1 ml water and DMAc (5 ml) were all added. The mixture was heated at 100 C for 12 h. Then, the mixture was cooled, water was added and the product was extracted with ethylacetate. The organic layer was washed with brine, dried over Na2SO4, filtered, passed through celite, and analyzed by GC. Yields were based on corresponding aryl bromides.

Statistics shows that 4595-59-9 is playing an increasingly important role. we look forward to future research findings about 5-Bromopyrimidine.

Reference:
Article; Muthu Tamizh, Manoharan; Cooper, Benjamin F.T.; MacDonald, Charles L.B.; Karvembu, Ramasamy; Inorganica Chimica Acta; vol. 394; (2013); p. 391 – 400;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

A common compound: 698-29-3, name is 4-Amino-2-methylpyrimidine-5-carbonitrile,molecular formula is C6H6N4, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below., 698-29-3

(0273) To a solution of the compound of Reference Example 22 (50.0 g, 373 mmol) in formic acid (150 mL) were added water (65 mL) and Raney nickel (50 g). The mixture was heated under reflux for 15 minutes, cooled to room temperature, and filtrated through Celite, and then 28% ammonia water (220 mL) was added thereto under ice cooling. The mixture was stirred under ice cooling for 1 hour, and the precipitate was collected by filtration. The filter cake was washed with water (30 mL) and chloroform (30 mL¡Á2), and dried in vacuo. Furthermore, the filtrate was extracted with chloroform (200 mL) nine times, and the combined organic layer was concentrated. The resulting concentrated residue and the above-obtained filter cake were mixed, chloroform (70 mL) was added thereto, the mixture was stirred at room temperature for 30 minutes, hexane (210 mL) was added dropwise thereto over 10 minutes, and the mixture was stirred at room temperature for additional 1 hour. The precipitate was collected by filtration, washed with hexane/chloroform (3/1, 28 mL), and dried in vacuo to give the title compound (42.6 g, 83%). 1H-NMR (400 MHz, CDCl3) delta: 2.57 (3H, s), 5.98 (1H, brs), 8.15 (1H, brs), 8.57 (1H, s), 9.86 (1H, s).

With the rapid development of chemical substances, we look forward to future research findings about 698-29-3.

Reference:
Patent; Sumitomo Dainippon Pharma Co., Ltd.; YOSHINAGA, Hidefumi; URUNO, Yoshiharu; NAGATA, Hidetaka; HASHIMOTO, Masakazu; KATO, Taro; (43 pag.)US2016/122319; (2016); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

591-55-9, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 591-55-9, name is 5-Aminopyrimidine. This compound has unique chemical properties. The synthetic route is as follows.

To a mixture of 5-aminopyrimidine (CAS No. 591-55-9) (2.00 g, 21.0 mmol, 1 equivalent), triethylamine (14.7 mL, 105 mmol, 5 equivalents), EDC (7.26 g, 37.9 mmol, 1.8 equivalents), N,N-dimethyl-4-aminopyridine (0.257 g, 2.10 mmol, 0.1 equivalents) and DCM (60.0 mL) was added dropwise 3-(t-butoxy)-3-oxopropionic acid (CAS No. 40052-13-9) (4.86 mL, 31.5 mmol, 1.5 equivalents), and the mixture was stirred at room temperature for 3 days. To the reaction mixture were added water and ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified with silica gel column chromatography (silica gel, 25%-71% ethyl acetate/n-heptane) to afford the title compound (4.73 g). 1H-NMR (400 MHz, CDCl3) delta (ppm): 1.52 (s, 9H), 3.44 (s, 2H), 8.98 (s, 1H), 9.03 (s, 2H), 9.77 (br. s, 1H).

While traditionally a conservative industry, chemical producers will need to modernize their PR strategies to stay relevant.we look forward to future research findings about 591-55-9, 5-Aminopyrimidine.

Reference:
Patent; Eisai R&D Management Co., Ltd.; Kurokawa, Toshiki; Yoshida, Yu; Shin, Kogyoku; Kobayashi, Yoshihisa; Fukumoto, Hironori; Takeda, Kunitoshi; Ohashi, Yoshiaki; Kotake, Makoto; Shibuguchi, Tomoyuki; Watanabe, Toru; Kita, Yoichi; Hirota, Shinsuke; Fukuyama, Takashi; Kamada, Yasuaki; (59 pag.)US2017/137436; (2017); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 4595-59-9, name is 5-Bromopyrimidine. This compound has unique chemical properties. The synthetic route is as follows. 4595-59-9

[0745] Synthesis of pyrimidine-5-carbaldehyde: [0746] To a stirred solution of 5-bromopyrimidine (5 g, 31.66 mmol) in THF (50 mL) under argon atmosphere was added n-butyl lithium (2.2 g, 34.83 mmol) drop wise for 10 min at -78 C and stirred for 20 min. To this was added DMF (2.3 g, 31.66 mmol) at -78 C and stirred for 30 min. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was quenched with saturated ammonium chloride solution (40 mL) and extracted with EtOAc (3 x 40 mL). The combined organic extracts were washed with water (30 mL), brine (30 mL), dried over sodium sulfate, filtered and concentrated in vacuo to obtain the crude. The crude was purified through silica gel column chromatography using 25% EtOAc/ Hexanes to afford pyrimidine-5-carbaldehyde (200 mg, 3%) as colorless thick syrup. TLC: 30% EtOAc/ Hexanes (R 0.2).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,4595-59-9, 5-Bromopyrimidine, and friends who are interested can also refer to it.

Reference:
Patent; ENVIVO PHARMACEUTICALS, INC.; RIPKA, Amy; SHAPIRO, Gideon; MCRINER, Andrew, J.; BURSAVICH, Matthew, Gregory; WO2013/142269; (2013); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 3934-20-1 as follows., 3934-20-1

Example 1 : 2-Amino-4-chloropyrimidine (2) and 4-amino-2-chloropyrimidine (3) A suspension of 2,4-dichloropyrimidine (7.45 g, 50.0 mmol) in ammonium hydroxide (25%, 125 mL) is stirred at room temperature for 5 h. The appearance of the insoluble material changes from “salt-like” to “snow-like”. The precipitate is collected by filtration and dried in vacuo. The crude material is redissolved in MeOHiCH2CI2 (1 :1), adsorbed on SiO2 and purified by column chromatography (gradient cyclohexane:ethyl acetate from 5:1 to 1 :1) to yield 1.48 g (23%) of 2 and 1.73 g (26%) of 3 (TLC cyclohexane:ethyl acetate 3:1 , Rf (2)=0.45, Rf (3)=0.32). ESI-MS m/z 129.8 [M+H]+.

The chemical industry reduces the impact on the environment during synthesis 3934-20-1, I believe this compound will play a more active role in future production and life.

Reference:
Patent; COVALYS BIOSCIENCES AG; WO2006/114409; (2006); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The major producers of chemicals have been the Europe, Japan and China. Due to the growing call for a cleaner, greener environment, people will have to find innovative ways to maintain their relevance. Here is a compound 130049-82-0, name is 3-(2-Chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidine-4-one. This compound has unique chemical properties. The synthetic route is as follows. 130049-82-0

Example 2 Step-I: Preparation of Crude Paliperidone3-(2-Chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one (25 g) was added to ethanol (500 ml) at 25-30 C. under stirring. 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (20.1 g) and anhydrous sodium carbonate (38 g) were added to the above solution and then heated to 58-62 C. The resulting mass was stirred for 24 hours at 58-62 C. The reaction mass was cooled to 25 C., the inorganic material was filtered out and the resulting mass was washed with ethanol (75 ml). The ethanol was distilled under vacuum in water bath at 50 C. and the resulting residue was dissolved in methylene dichloride (1250 ml). The methylene chloride solution was washed with water (600 ml) 3 times and then dried with anhydrous sodium sulfate. Sodium sulfate was filtered and methylene dichloride was distilled under vacuum at 30-40 C. After complete distillation of methylene chloride, methanol (75 ml) was added to the residue, stirred for 2 hours, filtered the material and dried at 50 C. under high vacuum to yield 23.0 g of crude paliperidone (HPLC Purity: 95.11%; content of the keto impurity: 0.24 wt %).Step-II: Purification of PaliperidoneCrude paliperidone (23 g, obtained in step-I) was heated with dimethylformamide (115 ml) under stirring at 56 C. for 3 hours. The resulting mass was cooled to 25 C., and material was filtered and washed initially with dimethylformamide (23 ml) followed by methanol (23 ml). The resulting solid was heated to 56 C. with dimethylformamide (69 ml) and the mass was stirred for 3 hours and then cooled to 25 C. The resulting mass was filtered and washed initially with dimethylformamide (23 ml) followed by methanol (23 ml). The resulting solid was stirred with methanol (80 ml) for 3 hours, filtered, washed with methanol (80 ml), and then dried in an air oven at 25 C. for 3 hours to yield 13.6 g of paliperidone. The product was then dissolved in methanol (816 ml) at 65 C. to provide a clear solution and the solution was cooled to 50 C. This procedure was followed by the addition of activated carbon (3.5 gm). The resulting mass was stirred for 30 minutes at 50 C. and then filtered on a Hiflo bed. Sodium borohydride (10 mg) was added to the resulting solution and then stirred for 2 hours at 50 C. followed by distillation of methanol until the paliperidone crystallized out. The resulting solution was cooled to 25 C., filtered the material, washed with methanol and then dried at 60 C. under vacuum to yield 10.7 g of pure paliperidone (HPLC Purity: 99.95%; Content of the keto impurity: 0.035 wt %).; Example 4 Purification of PaliperidoneCrude paliperidone (20 g, obtained in step-I of example 2) was heated with sulfolane (100 ml) under stirring at 60 C. for 3 hours, the resulting mass was cooled to 25 C. The material was filtered and washed initially with sulfolane (20 ml) followed by methanol (20 ml). The filtered solid was slurried with sulfolane (60 ml), the resulting slurry was heated to 60 C. under stirring and then maintained for 3 hours. The resulting mass was cooled to 25 C., filtered the solid and washed initially with sulfolane (20 ml) followed by methanol (20 ml). The filtered solid was stirred with water (200 ml) for 1 hour and then the material was filtered and washed with water (100 ml) followed by methanol (50 ml). The resulting solid was then stirred with methanol (100 ml) for 1 hour, and the material was filtered and washed with methanol (50 ml) and then dried in an air oven at 25 C. for 3 hours to yield 13.3 g of paliperidone. The product was then dissolved in methanol (800 ml) at 65 C. to provide a clear solution. The solution was cooled to 50 C. followed by the addition of silica gel (20 g) with stirring for 30 minutes at 50 C. The resulting solution was filtered to remove the silica gel. Sodium borohydride (10 mg) was added to the resulting filtrate and the temperature was maintained for 2 hours at 50 C. Methanol was distilled until paliperidone crystallized out and the resulting solution was cooled to 25 C. The separated solid was filtered, washed with methanol and then dried at 60 C. under vacuum to yield 11 g of pure paliperidone (HPLC Purity 99.7%; Content of the keto impurity at 0.96 RRT: 0.02 wt %).

Statistics shows that 130049-82-0 is playing an increasingly important role. we look forward to future research findings about 3-(2-Chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidine-4-one.

Reference:
Patent; ACTAVIS GROUP PTC EHF; US2009/247553; (2009); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

156-81-0, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 156-81-0, name is Pyrimidine-2,4-diamine. This compound has unique chemical properties. The synthetic route is as follows.

2-[(2-aminopyrimidin-4-yl)amino]-1,3-thiazole-5-carbonitrile (2-3) 2,4-Diaminopyrimidine, 2-1, (0.1 g, 0.908 mmol) was dissolved in DMF and then sodium hydride (0.036 g of a 60% dispersion, 0.908 mmol) was added and stirred for 15 minutes at 25 C. and then 2-chloro-1,3-thiazole-5-carbonitrile, 2-2, (0.131 g, 0.908 mmol) was added. This was heated at 100 C. for 2 hours. After this time the reaction was diluted with 4 mL of methanol and loaded onto a C18 prep lc column. The product, 2-3, was isolated via lyophilization from dioxane. 1H-NMR (DMSO): 8.42 ppm (s, 1H); 8.10 ppm (d, 1H); 6.45 ppm (d, 1H). 4,6-diaminopyrimidine hemisulfate, hemisulfate of 3-1, (0.10 g, 0.314 mmol) and diisopropylethylamine (0.122 g, 0.942 mmol) were suspended in n-butanol (1 mL) and then solid 2-chloro-1,3-thiazole-5-carbonitrile 2-2 (0.091 g, 0.628 mmol) was added and heated at 125 C. for 18 hours. The product 3-2 was purified on C18 preparative hplc and the product was isolated upon evaporation. Hi-Res MS: calc: 219.0448 found: 219.0448. 1H-NMR (DMSO): 8.36 ppm (s, 1H); 8.26 ppm (s, 1H); 7.20 ppm (s, 1H); 6.12 pm (s, 1H).

While traditionally a conservative industry, chemical producers will need to modernize their PR strategies to stay relevant.we look forward to future research findings about 156-81-0, Pyrimidine-2,4-diamine.

Reference:
Patent; Bilodeau, Mark T.; Hartman, George D.; Hoffman JR., Jacob M.; Sisko, John T.; Manley, Peter J.; Smith, Anthony M.; Tucker, Thomas J.; Lumma JR., William C.; Rodman, Leonard; US2002/137755; (2002); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

932-52-5, Adding a certain compound to certain chemical reactions, such as: 932-52-5, 5-Aminopyrimidine-2,4(1H,3H)-dione, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound, 932-52-5, blongs to pyrimidines compound.

General procedure: A suspension of 5-aminouracil 1 (1 mmol) in dry pyridine (7.5 mL) was cooled to 0 C and the appropriate sulfonyl chloride (1 mmol) was added. The reaction mixture was stirred at room temperature until the TLC showed the reaction was completed (1.5-20 h). The solvent was removed under reduced pressure and the crude product was recrystallized from methanol or aqueous methanol to afford the product.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,932-52-5, its application will become more common.

Reference:
Article; Ismaili, Hamit; Ban, ?eljka; Mati?, Josipa; Safti?, Dijana; Juki?, Marijana; Glava?-Obrovac, Ljubica; ?ini?, Biserka; Croatica Chemica Acta; vol. 92; 2; (2019); p. 269 – 277;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 59989-18-3 as follows., 59989-18-3

under protection of argon, the cuprous iodide (0.02 mmol, 3.8 mg), four-triphenylphosphine palladium (0.02 mmol, 23 mg) and 1 – octane, 5 – ethynyl uracil (0.4 mmol, 99.6 mg) are added to the 4, 4 – di (3, 4, 5 – c (dodecyl) benzyl alkyne base) – 2, 6 – diiodosalicylic -8 – (3, 4, 5 – c (dodecyl) phenyl) beryllium two pyrrole in (0.2 mmol, 480 mg). For syringe triethylamine (5 ml) is injected into the mixture and, in the 70 C reaction in oil bath for four hours. Thin layer chromatographic detection, to be the reaction is complete, the reaction also adding 20 ml water quenching reaction. Ethyl ether (3 ¡Á 40 ml) extraction product, organic phase water (3 ¡Á 40 ml) washing three times. Anhydrous magnesium sulfate drying, pressure reducing and steaming and in addition to the solvent. The crude product column chromatographic separation and purification, showering liquid to dichloromethane: ethyl acetate=50:1, volume ratio. The product methanol recrystallization is purple solid, 179.5 mg, yield is 68%.

The chemical industry reduces the impact on the environment during synthesis 59989-18-3, I believe this compound will play a more active role in future production and life.

Reference:
Patent; Tianjin University; Chen Zhijian; Liu Ping; (17 pag.)CN107056829; (2017); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia