Pyrimidines

Electric Literature of 57489-77-7, 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.57489-77-7, name is 5,7-Dichloropyrazolo[1,5-a]pyrimidine, molecular formula is C6H3Cl2N3, molecular weight is 188.01, as common compound, the synthetic route is as follows.

Step C – Synthesis of 5-chloropyrazolo[ 1 ,5-a]pyrimidin-7-amine (Int-9c)To 5,7-dichloropyrazolo[ 1 ,5-a]pyrimidine (Int-9b, 7.6 g, 40.4 mmol) in a sealed vessel was added NH4OH (100 mL). The vessel was then sealed and heated at 85 0C for 2.5 hours, at which time the consistency of the white solid had changed (from foamy white solid to free-flowing white solid). The vessel was removed from the heat source and allowed to cool to room temperature overnight. On cooling, the contents of the vessel were collected and dried by vacuum filtration giving 5-chloropyrazolo[l,5- a]pyrimidin-7-amine (Int-9c) as a yellow-tinged white solid (6.8 g, 40.3 mmol, 100%).

The chemical industry reduces the impact on the environment during synthesis 57489-77-7, I believe this compound will play a more active role in future production and life.

Reference:
Patent; SCHERING CORPORATION; CHENG, Cliff, C.; ZENG, Hongbo; SHIPPS, Jr., Gerald, W.; DENG, Yongqi; MENG, Zhaoyang; ZHAO, Lianyun; NAN, Yang; SUN, Binyuan; LIU, Duan; REDDY, Panduranga, A.; SIDDIQUI, M., Arshad; WO2011/2887; (2011); A1;,
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Pyrimidine – Wikipedia

Adding a certain compound to certain chemical reactions, such as: 5466-43-3, 2,4-Dichloro-6,7-dihydro-5H-cyclopenta[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, 5466-43-3, blongs to pyrimidines compound. Recommanded Product: 5466-43-3

To a stirred solution of 2,4-dichioro-6,7-dihydro-5H- cyclopenta[dlpyrimidine (600 mg, 3.17 mmoi) in i-PrOH (50 mL) were added TEA (963 mg, 9.52 mmol) and 3-4arninomethyi)phenoi (469 mg, 3.8() mmol).The mixture was stirred at 110C under N2 atmosphere for 15 hrs, cooled to it,concentrated and purified on silica gel column (hexane/ethyl acetate) to affbrd3 -(((2chioro-6,7-dihydro5Hcyciopenta[dipvriniidin-4-yI)arnino)methyI)phenoi(370 mg, 38%) as a white solid LCMS (M-F-W) ith: Calcd: 276.1; Found:276.1.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,5466-43-3, its application will become more common.

Reference:
Patent; CLEAVE BIOSCIENCES, INC.; ZHOU, Han-Jie; WUSTROW, David; (498 pag.)WO2016/200840; (2016); A1;,
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Application of 1337532-51-0, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 1337532-51-0, name is 5-Bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine, molecular formula is C7H7BrN4, The compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

To a stirred solution of 1-(4-bromophenyl)-3-(2,6-dimethylpyrimidin-4-yl)pyrrolidin-2-one (0.6 g, 1.734 mmol, 1.0 equiv), was added bis(pinacolato)diboron (0.441 g, 1.7 mmol, 1.0 equiv), and potassium acetate (0.510 g, 5.2 mmol, 3.0 equiv), and the mixture was degassed with Argon for 10 minutes, PdCI2(dppf)-CH2CI2 adduct (0.071 g, 0.09 mmol, 0.05 equiv) was added and again degassed with Argon for 10 minutes. The reaction mixture was stirred for 3 hours at 100 C in a sealed vessel. The reaction was cooled to room temperature. 5-bromo-7-methyl-7/-/-pyrrolo[2,3-c]pyrimidin-4-amine (0.394 g, 1.734 mmol, 1.0 equiv) and saturated aqueous NaHC03 (6 mL) were added, and Argon gas was bubbled through the mixture for 10 minutes. PdCl2(dppf)-CH2Cl2 adduct (0.071 g, 0.09 mmol, 0.05 equiv) was added, the vessel was sealed, and the reaction mixture was stirred overnight at 100 C. The crude mixture was filtered through celite and the filtrate was dried over Na2S04 and concentrated. Purification: Crude material was purified by flash column chromatography using silica gel column, compound was eluted at 8-10 % MeOH :DCM as mobile phase.yield: (0.055 g, 7.7 %) as off white solid. LCMS (ES) m/z = 414.2 [M+H]+. H NMR (400 MHz, CDCI3) delta 2.50 (s, 3 H), 2.57 – 2.61 (m, 1 H), 2.67 (s, 3 H), 2.71 – 2.78 (m, 1 H), 3.84 (s, 3 H), 3.91 – 4.00 (m, 2 H), 4.09 – 4.15 (m, 1 H), 5.23 (br s, 2 H), 6.94 (s, 1 H), 7.13 (s, 1 H), 7.49 (d, J=8.40 Hz, 2 H), 7.76 (d, J=8.0 Hz, 2 H), 8.33 (s, 1 H).

According to the analysis of related databases, 1337532-51-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; AXTEN, Jeffrey M.; MEDINA, Jesus Raul; WO2015/136463; (2015); A1;,
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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 1337532-51-0, name is 5-Bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine. This compound has unique chemical properties. The synthetic route is as follows. name: 5-Bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

To a stirred reaction mixture of 3-(6-methylpyridin-2-yl)-1-(4-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)phenyl)pyrrolidin-2-one was added 5-bromo-7-methyl-7/-/-pyrrolo[2,3- d]pyrimidin-4-amine (0.479 g, 2.1 mmol, 1.0 equiv) of and 8 ml of sat. NaHC03 solution under argon atmosphere, followed by addition of PdCl2(dppf)-CH2Cl2 adduct (0.086 g, 0.11 mmol, 0.05 equiv) under argon atmosphere, the reaction mixture was heated to 100 C and stirred for overnight. Reaction mixture was monitored by LCMS and after consumption of starting material, Reaction mixture was filtered through celite and washed with DCM. The filtrate was and dried over Na2S04 and concentrated to get crude product. Crude product was purified by flash chromatography on Silica gel and compound was eluted with 2% MeOH/DCM as impure fraction, it was re purified by prep HPLC(Column :Column : Inertsil ODS 3V (250 mm X 4.6 mm X 5 mic), Mobile phase (A) : 0.01 % Ammonia in water, Mobile phase(B) : ACN, Flow rate : 1.0 mL/min) to get 1-4-(4-amino-7- methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl)-3-(6-methylpyridin-2-yl)pyrrolidin-2-one as off-white solid, yield (0.07g, 10%). LCMS (ES) m/z = 399.2 [M+H]+. H NMR (400 MHz, DMSOd6) delta 2.44 (s, 3 H), 2.49 – 2.53 (m, 2 H), 3.73 (s, 3 H), 3.92 – 4.07 (m, 3 H), 6.03 (br s, 2 H), 7.13 – 7.20 (m, 2 H), 7.29 (s, 1 H), 7.46 (d, J=8.4 Hz, 2 H), 7.65 (t, J=7.6 Hz, 1 H), 7.79 (d, J=8.4 Hz, 2 H), 8.14 (s, 1 H).

With the rapid development of chemical substances, we look forward to future research findings about 1337532-51-0.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; AXTEN, Jeffrey M.; MEDINA, Jesus Raul; WO2015/136463; (2015); A1;,
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Application of 3289-50-7 ,Some common heterocyclic compound, 3289-50-7, molecular formula is C6H9N3O2, 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.

EXAMPLE 1 N-[(2,6-dimethoxypyrimidin-4-yl)aminocarbonyl]-2-methylbenzenesulfonamide To a stirred mixture of 2.40 g of 4-amino-2,6-dimethoxypyrimidine in 40 ml methylene chloride at ambient temperature and pressure was slowly added 3.0 g of 2-methylbenzenesulfonylisocyanate. The reaction was stirred 40 minutes, filtered, and the solid thereby obtained was washed with a small amount of acetonitrile; yield 4.0 g, m.p. 174-175, NMR (DMSO-d6) relative to tetramethylsilane: delta 2.77, S, area 30; delta 4.05, S, area 60; delta 6.85, S, area 89; delta 7.7-8.6, multiplets, area 45; delta 10.00, S, area 9.

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles. 3289-50-7, 4-Amino-2,6-dimethoxypyrimidine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; E. I. Du Pont de Nemours and Company; US4221585; (1980); A;,
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Pyrimidine – Wikipedia

As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 13627-49-1, name is 2-Methylpyrimidine-4-carboxylic acid, molecular formula is C6H6N2O2, The compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below. SDS of cas: 13627-49-1

Example 76cis 2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide Example 76 was also prepared from intermediate 33 via the process of Scheme 1, supra, as follows:In a round-bottom flask was charged with cis-7-amino-2-(3,5-difluoro-phenyl)-2-aza-spiro[4.5]decan-1-one. HCl (10.8 g, 34.1 mmol), 2-methylpyrimidine-4-carboxylic acid (4.71 g, 34.1 mmol), and BOP (15.1 g, 34.1 mmol). Methylene chloride (218 mL) was added, and the mixture was cooled at 0 C. Triethylamine (14.2 mL, 102 mmol) was added dropwise. The mixture was warmed up to rt and stirred at rt overnight. The mixture was diluted with methylene chloride (100 mL) and water (50 mL). The aqueous layer was extracted with CH2Cl2 (100 mL). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue obtained was crystallized from ethyl acetate to afford 8.8 g (77%) of the title compound cis 2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide: 1H NMR (400 MHz, CDCl3): delta8.85 (d, J=5.0 Hz, 1H), 8.10 (d, J=8.1 Hz, 1H), 7.89 (d, J=5.4 Hz, 1H), 7.28-7.35 (m, 2H), 6.60 (tt, J=8.8, 2.5 Hz, 1H), 4.07-4.18 (m, 1H), 3.74-3.80 (m, 2H), 2.79 (s, 3H), 2.07-2.28 (m, 3H), 1.89-1.97 (m, 2H), 1.55-1.85 (m, 4H), 1.37-1.48 (m, 1H). ESI-MS m/z: 401 (M+H)+.

With the rapid development of chemical substances, we look forward to future research findings about 13627-49-1.

Reference:
Patent; H. LUNDBECK A/S; US2011/98299; (2011); A1;,
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Pyrimidine – Wikipedia

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;,
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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;,
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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