Day: May 8, 2021

Synthetic Route of 26305-13-5, 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. 26305-13-5, name is 2,4-Dihydroxy-5,6-dimethylpyrimidine. A new synthetic method of this compound is introduced below.

2,4-Dichloro-5,6-dimethylpyrimidine (RJ1-008) (WO2013/123401): A mixture of RJ1-006 (4.00 g, 28.5 mmol), phosphorus(V) oxychloride (60 mL, 0.642 mol), and dimethylformamide (0.08 mL, 1.03 mmol) was heated to reflux at 110 C for 23 hours. The reaction mixture was then cooled to ambient temperature and evaporated. Toluene (80 mL) was added to the residue and the resulting mixture was concentrated. Cold water with ice (160 mL) was added to the residue, and the mixture was extracted with chloroform (3 x 60 mL). The combined organic layers were washed with brine (2 x 150 mL), dried over sodium sulfate, filtered, and concentrated to provide RJ1-008 as a pale yellow solid (4.37 g, 87%). m.p. = 68-70 C. XH NMR (400 MHz, CDCb) delta 2.55 (s, 3H), 2.34 (s, 3H). LRMS (ESI+) m/z 177.1

At the same time, in my other blogs, there are other synthetic methods of this type of compound,26305-13-5, 2,4-Dihydroxy-5,6-dimethylpyrimidine, and friends who are interested can also refer to it.

Reference:
Patent; H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.; SCHOeNBRUNN, Ernst; LAWRENCE, Nicholas, J.; LAWRENCE, Harshani, R.; (257 pag.)WO2016/22460; (2016); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 428854-24-4, 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 428854-24-4 as follows.

Example 48 4-Amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pteridin-7(8H)-one 300 mg (0.856 mmol) of the compound from example 1A were dissolved in 20 ml of ethanol, and 187 mul (0.942 mmol) of a 50% solution of ethyl glyoxalate in toluene were added. The mixture was heated to reflux for 1 h, 2 drops of concentrated sulfuric acid were added and the mixture was heated to reflux for a further 16 h. The precipitate was filtered off and dried under high vacuum. 83 mg of the title compound were obtained (23% of theory). LC-MS (method 3): Rt=0.93 min; MS (EIpos): m/z=389 (M+H)+. 1H NMR (400 MHz, DMSO-d6): delta [ppm]=5.85 (s, 2H), 7.13-7.26 (m, 3H), 7.34-7.39 (m, 1H), 7.43 (dd, 1H), 7.74-8.01 (m, 3H), 8.66 (dd, 1H), 9.17 (dd, 1H), 12.86 (s, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,428854-24-4, its application will become more common.

Reference:
Patent; BAYER INTELLECTUAL PROPERTY GMBH; Follmann, Markus; Stasch, Johannes-Peter; Redlich, Gorden; Ackerstaff, Jens; Griebenow, Nils; Knorr, Andreas; Wunder, Frank; Li, Volkhart Min-Jian; Baerfacker, Lars; Weigand, Stefan; US2014/148433; (2014); 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 893755-98-1, name is 1-(Pyrimidin-2-yl)piperidin-4-ol. This compound has unique chemical properties. The synthetic route is as follows. name: 1-(Pyrimidin-2-yl)piperidin-4-ol

EXAMPLE 89: Preparation of (2R,3R)-2-(2,4-difluorophenyl)-3-((1-(pyrimidin-2-yl)piperidin-4-yl)oxy)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol To a solution of 1-(pyrimidin-2-yl)piperidin-4-ol (19.4 mg, 0.08 mmol) in N,N-dimethylformamide (0.5 mL) was added potassium tert-butoxide (10.7 mg, 0.01 mmol), followed by stirring at room temperature for 2 hrs. The resulting solution was mixed with 1-(((2R,3R)-2-(2,4-difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole (20.0 mg, 0.08 mmol) and anhydrous calcium carbonate (13.2 mg, 0.01 mmol) and stirred at room temperature for one hr. The resulting reaction mixture was diluted with ethyl acetate, and washed with a saturated aqueous ammonium chloride solution and then with saline to separate an organic solvent layer. The organic solvent layer was dried over anhydrous magnesium sulfate and concentrated by evaporation at reduced pressure. The concentrate was purified using silica gel chromatography to afford the title compound (yield 21 %).1H-NMR(CDCl3, 300 MHz) delta 8.30(d, 1H, J=1.4Hz), 8.28(d, 1H, J=2.6Hz), 7.87(s, 1H), 7.62(s, 1H), 7.37(d, 1H, J=1.2Hz), 7.22-7.13(m, 1H), 6.99-6.86(m, 2H), 5.38(s, 1H), 4.45-4.28(m, 2H), 3.99-3.91(m, 1H), 3.35-3.26(m, 2H), 2.00-1.92(m, 2H), 1.59-1.47(m, 2H), 1.33-1.31(dd, 3H, J=3.1Hz, J=3.4Hz).

With the rapid development of chemical substances, we look forward to future research findings about 893755-98-1.

Reference:
Patent; DAEWOONG PHARMACEUTICAL CO., LTD.; PARK, Joon Seok; YU, Kyung A; YOON, Yun Soo; HAN, Mi Ryeong; KIM, Ji Duck; WO2011/99804; (2011); A2;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 147118-40-9, Adding some certain compound to certain chemical reactions, such as: 147118-40-9, name is Rosuvastatin methyl ester,molecular formula is C23H30FN3O6S, 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 147118-40-9.

EXAMPLE 2; PREPARATION OF N,N’-DIBENZYLETHYLENEDIAMINEROSUVASTATIN SALT; Rosuvastatin methyl ester was (1 g) was dissolved in ethanol (15 ml) at 25-300C and cooled to 0-50C and treated with aqueous sodium hydroxide (0.1 N, 20 ml) at 0-50C. The temperature of the reaction mass was raised to 25-300C and stirred for 1 hr. Ethanol was evaporated from the reaction mass under reduced pressure at 40-450C and the resulting aqueous layer was diluted further with 15 ml of DM water. This aqueous layer containing rosuvastatin was washed with 30percent v/v ethyl acetate/toluene (50 ml) at 25-300C and treated with aqueous solution of N,N’- dibenzylethylenediamine diacetate (0.9 g in 5 ml). The resulting suspension was stirred for 1 hr for complete precipitation and the precipitated product was filtered, slurry washed with ethyl acetate (20 ml) and dried under vacuum at 40-450C. Dry wt. 0.68 g; Chromatographic purity (HPLC): 99.28percent, Anti isomer: 0.59percent.; EXAMPLE 3PREPARATION OF N,N’-DIBENZYLETHYLENEDIAMINEROSUVASTATINA solution of rosuvastatin methyl ester (5 g) in ethanol (70 ml) was treated with aqueous sodium hydroxide (0.1N, 88 ml) at 0-50C and the temperature of the reaction was raised to 300C and stirred for 1 h. Ethanol from the reaction mass was evaporated at 40-450C. This aqueous layer was washed with 30 v/v ethyl acetate/toluene (3 x 25 ml) and treated with an aqueous solution of N,N’-dibenzylethylenediamine diacetate(1.8 g in 10 ml water). The resulting mass was further stirred for a period of 2 h, filtered, slurry washed with ethyl acetate (30 ml) and dried under vacuum at 40-450C. Dry Wt. 3.3 g, Chromatographic purity: 99.48 percent, Anti isomer: 0.47percent.

According to the analysis of related databases, 147118-40-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AUROBINDO PHARMA LIMITED; WO2008/38132; (2008); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.287714-35-6, name is Methyl 2-chloropyrimidine-5-carboxylate, molecular formula is C6H5ClN2O2, molecular weight is 172.57, as common compound, the synthetic route is as follows.Recommanded Product: 287714-35-6

To a solution of 6-(tert-butylsulfonyl)-N-(5-fluoro-lH-indazol-3-yl)-7-(2-(piperazin-l- yl)ethoxy)quinolin-4-amine (120 mg, 0.23 mmol) in NMP (2 mL) was added methyl 2- chloropyrimidine-5-carboxylate (47 mg, 0.27 mmol), and sodium bicarbonate (57 mg, 0.68 mmol) and the reaction was stirred at 110 C for lh. The residue was subjected directly to purification by flash chromatography (30g pre-packed C-18 SNAP cartridge: 30% to 85% acetonitrile (0.1% ammonia) in water (10 mM ammonium bicarbonate)). The desired fractions were combined and concentrated to afford the title compound (106 mg, 0.16 mmol, 70 % yield). LCMS T= 1.15 min, ES+ve 663.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,287714-35-6, Methyl 2-chloropyrimidine-5-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; CASILLAS, Linda N.; HARLING, John David; MIAH, Afjal Hussain; SMITH, Ian Edward David; RACKHAM, Mark David; (204 pag.)WO2017/182418; (2017); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 131860-97-4, 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 131860-97-4, name is (E)-Methyl 2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)-3-methoxyacrylate. This compound has unique chemical properties. The synthetic route is as follows.

Dimethylacetamide (DMAA, 400ml), 2-Cyanophenol (0.2M, 28g) and NaOH (0.225M, 9g) were placed at ambient temperature into the three-necked IL flask equipped with stirrer, condenser and thermometer. Half the amount of DMAA containing water traces was distilled at vacuum 20mbar/60-65C and the mixture was kept at vacuum 20mbar/ room temperature for Ih. The same amount of prime DMAA was added and Compound (I) (0.2M, 64g) was fed into the flask.The reaction mixture was heated to 100 C and kept at these conditions for 5 hours (monitored by HPLC – conversion of Compound (I) to Azoxystrobin 98-99%).DMAA was distilled at vacuum 20mbar/65-70C. At the end of the distillation the temperature can be increased up to 90-100C.40Og Butylacetate (BuAc) and 20Og water were added to the reaction mixture at 50-60C, the temperature was increased to 80C and stirred 10-15min. The water phase was separated at 800C to remove DMAA traces and inorganic salts.For crystallization the BuAc phase was slowly cooled from 800C to -5C. Filtration was done using filter No.2. The cake was washed with 60 ml cooled Butylacetate or methanol and further dried in oven at 80C during 15 hours. Azoxystrobin with purity 98-99% and a yield of 90-92% was obtained.

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 131860-97-4, (E)-Methyl 2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)-3-methoxyacrylate.

Reference:
Patent; MAKHTESHIM CHEMICAL WORKS LTD.; WO2008/75341; (2008); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Adding a certain compound to certain chemical reactions, such as: 74901-69-2, 2,4-Dichloro-6,7-dihydrothieno[3,2-d]pyrimidine, 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, Quality Control of 2,4-Dichloro-6,7-dihydrothieno[3,2-d]pyrimidine, blongs to pyrimidines compound. Quality Control of 2,4-Dichloro-6,7-dihydrothieno[3,2-d]pyrimidine

Example 1 1.1 (2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)-(3-fluorophenyl)-amine (III-1) 4 g (II) are placed in 15 ml dimethylformamide, then 4.5 ml diisopropylethylamine and then 2.5 ml 3-fluorophenylamine are added. The reaction mixture is heated to 120 C., until no further reaction takes place, then cooled and evaporated down. The residue is mixed with water. The product is extracted with dichloromethane and purified by chromatography (silica gel, petroleum ether/ethyl acetate 80/20 to 60/40). 2.6 g (III-1) are obtained as a solid. Analytical HPLC (method A): RT=3.27 min.

The synthetic route of 74901-69-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; US2010/305102; (2010); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 32980-71-5, With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.32980-71-5, name is Perchloropyrimido[5,4-d]pyrimidine, molecular formula is C6Cl4N4, molecular weight is 269.9, as common compound, the synthetic route is as follows.

Connect a mineral oil valve rotating device, an impregnation thermometer, to a 4-cc bottle with a capacity of 100 cc.a vent and a drying tube, Add 7g piperidine and 30cc absolute ethanol to the bottle. Then, 2.7 g of tetrachloropyrimidopyrimidine was added with stirring. Increasing the reaction temperature to 32-35 C produces a moderate amount of basic steam. The powder reaction gradually changes from a yellow-gold-red crystal powder to a transparent granular powder.The tetrachloro compound is gradually added in 30 minutes. The reaction mixture was continuously stirred for 90 minutes and then allowed to stand for 24 hours. After the reaction was completed, it was observed that there was a bright yellow powder in the bright orange liquid, and the color of the liquid became more vivid when it was left standing. The precipitate was collected by filtration and washed with absolute ethanol to give 3.24 g of a yellow powder of unknown melting point which softened at 180 C and rapidly melted and decomposed at 240 C.The yellow powder was purified by adding 30 cc of dimethylformamide precooled at 0 C, and the dimethylformamide was turned into a deep red color. The precipitate was collected by suction filtration using a vacuum suction apparatus, and the residual dimethyl group was removed by washing with 10 cc of absolute ethanol. Formamide,The weight of the product is less than half the weight of the original material.The melting point is raised to 245 ~ 255 C, And softening occurs at 225 C. The average yield of the two chlorination reactions and subsequent reaction with piperidine is from 27 to 29%, based on the piperidine derivative, wherein the oxidized uric acid used in the chlorination reaction stage is in the form of its dried disodium salt.

Statistics shows that 32980-71-5 is playing an increasingly important role. we look forward to future research findings about Perchloropyrimido[5,4-d]pyrimidine.

Reference:
Patent; Suohao; Huan Xiaojun; Suo Hao; Qi Taotao; Jin Chunyan; Chen Yifei; (9 pag.)CN108752350; (2018); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 5194-32-1, 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 5194-32-1 as follows.

General procedure: General CoulinQ Procedure 5 POd3 (3 eq.) was added to a stirred solution of carboxylic acid A (1 .0 eq.) and amine B (1 .0 eq.) in pyridine (25 mL) at 0 C. The reaction mixturewas stirred for I h at RT. The reaction mixture was then filtered and the filtrate was diluted with ethyl acetate (100 mL) then washed with water and brine (100 mL each). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to obtain the crude product, which was then purified by preparative H PLC.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,5194-32-1, its application will become more common.

Reference:
Patent; FROST BIOLOGIC, INC.; SIDDIQUI-JAIN, Adam; WO2015/127284; (2015); A2;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of 60025-09-4 ,Some common heterocyclic compound, 60025-09-4, molecular formula is C5H3ClN4, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.

To a solution of 2-(1-(6-fluoro-4-(2-methoxyethylamino)-3-phenylquinolin-2-yl)ethyl)isoindoline-1,3-dione (73.9 mg, 0.157 mmol) in EtOH (2 mL) was added hydrazine (0.049 mL, 1.574 mmol) and the resulting mixture was heated to 60 C. for 20 min. The reaction mixture was allowed to warm to rt and solid was filtered. The filtrate was concd under reduced pressure and used crude for the next step. To the crude solution of 2-(1-aminoethyl)-6-fluoro-N-(2-methoxyethyl)-3-phenylquinolin-4-amine (25 mg, 0.074 mmol) in BuOH (2 mL) was added DIEA (0.033 mL, 0.189 mmol) and 4-amino-6-chloropyrimidine-5-carbonitrile (24.33 mg, 0.157 mmol) and the resulting mixture was stirred at 110 C. overnight. The reaction mixture was cooled to rt and purified via HPLC.4-Amino-6-(1-(6-fluoro-4-((2-methoxyethyl)amino)-3-phenyl-2-quinolinyl)ethyl)amino)-5-pyrimidinecarbonitrile1H-NMR (400 Hz, CD3OD) delta ppm 1.53 (3H, d, J=7.24 Hz) 3.23 (2H, s) 3.33 (2H, m) 3.41 (2H, m) 4.99 (1H, m) 7.48 (1H, m) 7.64 (3H, m) 7.80 (2H, m) 8.03 (1H, s) 8.08 (1H, dd, J=9.39, 4.89 Hz) 8.22 (1H, dd, J=10.47, 2.64 Hz). Mass Spectrum (ESI) m/e=458 (M+1).4-Amino-6-(((1S)-1-(6-fluoro-4-((2-methoxyethyl)amino)-3-phenyl-2-quinolinyl)ethyl)amino)-5-pyrimidinecarbonitrile1H-NMR (400 Hz, CD3OD) delta ppm 1.30 (d, J=6.46 Hz, 3H) 3.18 (s, 3H) 3.19-3.22 (m, 2H) 3.28-3.31 (m, 2H) 5.25 (q, J=6.65 Hz, 1H) 7.37-7.41 (m, 1H) 7.43-7.47 (m, 1H) 7.48-7.55 (m, 2H) 7.55-7.61 (m, 2H) 7.82 (dd, J=10.76, 2.74 Hz, 1H) 7.94 (s, 1H) 8.01 (dd, J=9.29, 5.58 Hz, 1H). Mass Spectrum (ESI) m/e=458 (M+1).4-Amino-6-(((1R)-1-(6-fluoro-4-((2-methoxyethyl)amino)-3-phenyl-2-quinolinyl)ethyl)amino)-5-pyrimidinecarbonitrile1H-NMR (400 Hz, CD3OD) delta ppm 1.30 (d, J=6.65 Hz, 3H) 3.18 (s, 3H) 3.19 (d, J=1.56 Hz, 0H) 3.21 (d, J=5.28 Hz, 1H) 3.29-3.31 (m, 2H) 5.26 (q, J=6.52 Hz, 1H) 7.37-7.41 (m, 1H) 7.43-7.47 (m, 1H) 7.48-7.54 (m, 2H) 7.55-7.61 (m, 2H) 7.91-7.99 (m, 1H) 8.01 (dd, J=9.19, 5.67 Hz, 1H). Mass Spectrum (ESI) m/e=458 (M+1).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,60025-09-4, its application will become more common.

Reference:
Patent; AMGEN INC.; US2010/331306; (2010); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia