Day: January 19, 2021

Electric Literature of 1193-24-4 , The common heterocyclic compound, 1193-24-4, name is 4,6-Dihydroxypyrimidine, molecular formula is C4H4N2O2, 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 21:; 6-(3-f4-(2-terf-Butvl-6-cvclobutvl-pvrimidin-4-vl)-piperazin-1-vn-propoxv)-pyrimidin-4-ol; 1.5 g of 2-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclobutyl-pyrimidine (4.27 mmol), 0.72 g of pyrimidine-4,6-diol (6.4 mmol) and 1.31 g of triethylamine in 30 ml of dimethylformamide were stirred for 16 h at 80C. The mixture was extracted with water and ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was purified by chromatography on silica gel using dichloromethane-methanol (1-10%). Fractions containing the product were combined. The solvents were evaporated and the oily residue was treated with acetonitrile. The precipitate was collected by filtration and dried to yield 0.27 g of the title compound.MS (ESI) m/z: 427.2 [M+H]+1H-NMR (DMSO): 5 [ppm] 8.1 (s, 1H), 6.4 (s, 1H), 5.5 (s, 1H), 4.15 (m, 2H), 3.6 (m, 4H), 3.4 (m, 2H), 2.4 (m, 6H), 2.25 (m, 2H), 2.15 (m, 2H), 1.95 (m, 1H), 1.85 (m, 2H), 1.8 (m, 1H), 1.3 (s, 9H).

The synthetic route of 1193-24-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ABBOTT GMBH & CO. KG; WO2006/15842; (2006); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of 13316-12-6, Adding some certain compound to certain chemical reactions, such as: 13316-12-6, name is 7-Chlorothiazolo[5,4-d]pyrimidine,molecular formula is C5H2ClN3S, 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 13316-12-6.

A solution of 4-[3-(1-aminoethyl)-5-chloro-2-ethoxy-6-fluorophenyl]pyrrolidin-2-one (30 mg, 0.333 mmol) and 7-chloro[1,3]thiazolo[5,4-d]pyrimidine (25.7 mg, 0.15 mmol) [AK-58025, Ark Pharm] in 1-butanol (6.6 mL) was treated with N,N-diisopropylethylamine (0.052 mL, 0.30 mmol) and heated at 114 C. for 2.5 h. The reaction mixture was then concentrated to a yellow residue. Purification by preparative LCMS (pH 2) afforded the title product (0.033 g, 60%) as a white solid as a mixture of four diastereoisomers. 1H NMR (300 MHz, DMSO-d6) delta 9.30 (s, 1H), 8.78 (d, J=8.4 Hz, 1H), 8.37 (d, J=1.8 Hz, 1H), 7.82 (s, 1H), 7.71 (d, J=8.3 Hz, 1H), 5.91-5.70 (m, 1H), 4.29-4.14 (m, 1H), 4.13-3.96 (m, 1H), 3.95-3.81 (m, 1H), 3.60 (dd, J=9.3, 9.3 Hz, 1H), 3.26 (dd, J=7.8, 7.3 Hz, 1H), 2.42-2.21 (m, 2H), 1.59-1.32 (m, 6H); LCMS calculated for C19H20ClFN5O2S (M+H)+: m/z=436.1. found: 435.9.

According to the analysis of related databases, 13316-12-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; INCYTE CORPORATION; Li, Yun-Long; Combs, Andrew P.; US2015/361094; (2015); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 308348-93-8, 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. 308348-93-8, name is Methyl 2-aminopyrimidine-5-carboxylate. A new synthetic method of this compound is introduced below.

To a mixture of 2-bromo-1,1-diethoxyethane (100.6 g, 0.5 1 mol) and methyl 2-aminopyrimidine-5-carboxylate (63 g, 0.41 mol) in ethanol (300 mL) was added concentrated HBr (40%) (55 g). The reaction mixture was heated to reflux for 3 h under N?. After cooling to rt, the mixture was further cooled with an ice-water bath. The resulting precipitate was collected by vacuum filtration and dried under vacuum overnight to give the desired product (92 g, 87%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,308348-93-8, its application will become more common.

Reference:
Patent; GENENTECH, INC.; FORMA TM, LLC; BAIR, Kenneth W.; BAUMEISTER, Timm R.; BUCKMELTER, Alexandre J.; CLODFELTER, Karl H.; DRAGOVICH, Peter; GOSSELIN, Francis; GUNZNER-TOSTE, Janet; HAN, Bingsong; LIN, Jian; LIU, Xiongcai; REYNOLDS, Dominic J.; SMITH, Chase C.; WANG, Zhongguo; ZAK, Mark; ZHANG, Yamin; ZHAO, Guiling; ZHENG, Xiaozhang; YUEN, Po-Wai; WO2013/127266; (2013); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Electric Literature of 26032-72-4, 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 26032-72-4 as follows.

As shown in Figure 3-step i, a mixture of phenylboronic acid (1.22 g),2,4,6-trichloropyrimidine (compound 1011), tetrakis(triphenylphosphine) palladium(O) and 2N sodium carbonate (15 mL) in DME (25 mL) was heated at 80 0C overnight. After cooling to it, addition of water (30 mL), extraction with dichloromethane (3 x 20 mL), drying and evaporation, purification by column chromatography (SiO2, 10-20% ethyl acetate in hexane) afforded the desired product, 6-phenyl-2,4-dichloropyrimidine (compound 1012) (0.544 g). As shown in Figure 3-step ii, compound 1012 (0.34 g) was mixed with (,S)-2-amino-N-(2,2,2- trifluoroethylpropanamide (0.3 g) and diisopropylethylamine (0.63 mL) in isopropanol (5 mL) and the reaction mixture heated at 80 0C overnight. Evaporation gave a residue, which after aqueous workup and purification (SiO2, 20% ethyl acetate/hexane) produced 2-(2- chloro-6-phenyl-pyrimidin-4-ylamino)-nu-(2,2,2-trifluoro-ethyl)propionamide (compound 1013) (0.165 g). As shown in Figure 3-step iii, compound 1013 (29 mg), 5-(4,4,5,5- Tetramethyl-[l,3,2]dioxaborolan-2-yl)-7-(toluene-4-sulfonyl)-7H-pyrrolo[2,3-d]pyrimidine (compound 1005), PdCl2dppf2 (7 mg), and potassium phosphate (32 mg) were heated in 1,4- dioxane (2 mL) at 80 0C overnight. To the reaction was added aqueous lithium hydroxide solution (2 mL). After heating at 600C for Ih, water (20 mL) was added. Extraction with dichloromethane (3X), drying, evaporation and purification (SiO2, 50-100% ethyl acetate/hexane) gave 3.7 mg of 2-[6-phenyl-2-(7eta-pyrrolo[2,3-d]pyrimidin-5-yl)-pyrimidin- 4-ylamino]-N-(2,2,2-trifluoro-ethyl)-propionamide (compound 18).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,26032-72-4, its application will become more common.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2007/41130; (2007); A2;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 130645-48-6, 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 130645-48-6, name is 2-Bromo-4-methylpyrimidine. This compound has unique chemical properties. The synthetic route is as follows.

PREPARATION EXAMPLE 54 Synthesis of 4-methyl-2-(3,4,5-Trimethoxyphenyl)-pyrimidine 2-Bromo-4-methylpyrimidine (1.5 g) and 3,4,5-trimethoxyphenylboronic acid (1.83 g) were reacted in the same manner as in Preparation Example 1 to obtain the title compound. Yield: 1.49 g (67%). 1H-NMR (400 MHz, CDCl3) delta: 2.57 (s, 3H), 3.92 (s, 3H), 3.99 (s, 6H), 7.01 (d, 1H, J=5.1 Hz), 7.77 (s, 2H), 8.61 (d, 1H, J=5.1 Hz).

According to the analysis of related databases, 130645-48-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Kowa Co., Ltd.; US6509329; (2003); B1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 851984-15-1, 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.851984-15-1, name is 6-Chloro-5-fluoropyrimidin-4-amine, molecular formula is C4H3ClFN3, molecular weight is 147.54, as common compound, the synthetic route is as follows.

To a solution of trans-3 -((3 -chloro-S-(trifluoromethyl)phenyl)amino) -2-oxo- [1,3 ?-bipiperidine] -4?-carboxamide 13 (42 mg, 0.10 mmol, 1.0 equiv) in 1-butanol (2 mL), 6-chloro-S-fluoropyrimidin-4-amine (18 mg, 0.12 mmol, 1.2 equiv) was added DIPEA (26 mg, 0.20 mmol, 2.0 equiv). The reaction solution was stirred at 120 C for 16 h. The mixture was diluted with EtOAc (20 mL), washed with H20 (10 mL) and brine (10 mL), dried (Na2504), filtered, and concentrated in vacuo. The crude was by purified by pre-HPLC (MeOHIH2O with 0.05% TFA as mobile phase) to give the compound (trans)- 1 ?-(6-amino-S -fluoropyrimidin-4-yl)-3 -((3 -chloro-S – (trifluoromethyl)phenyl)amino)-2-oxo-[ 1,3 ?-bipiperidine] -4?-carboxamide 14 (44 mg, yield:83%) as a yellow solid. ESI-MS (M+H) : 530.0. HPLC: (214 nm: 100%, 254 nm: 100%). ?H NMR (400 MHz, CD3OD) 5: 7.97 (s, 1H), 6.84 (s, 1H), 6.81 (s, 1H), 6.76 (s, 1H), 4.58-4.52 (m, 2H), 4.09-4.03 (m, 1H), 3.52-3.35 (m, 3H), 3.29-3.27 (m, 4H), 3.12-3.05 (m, 1H), 2.24-2.17 (m,1H), 2.02-1.91 (m, 3H), 1.80-1.63 (m, 2H).

Statistics shows that 851984-15-1 is playing an increasingly important role. we look forward to future research findings about 6-Chloro-5-fluoropyrimidin-4-amine.

Reference:
Patent; BIOGEN MA INC.; SUNESIS PHARMACEUTICALS, INC.; MACPHEE, J. Michael; NEUMAN, Linda L.; (89 pag.)WO2018/17153; (2018); 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. 873-83-6, name is 6-Aminopyrimidine-2,4(1H,3H)-dione. This compound has unique chemical properties. The synthetic route is as follows. name: 6-Aminopyrimidine-2,4(1H,3H)-dione

To a suspended solution of 6-aminouracil (12.7 g, 100 mmol) and sodium acetate (8.2 g, 100 mmol) in H20 (100 mL) at a temperature of 70-75 ¡ãC was added a solution of chloroacetaldehyde (50percent in water, 23.6 g, 150 mmol). The resulting reaction mixture was stirred at 80 ¡ãC for 20 mm and then cooled to room temperature. The resulting solid was collected by filtration, washed with water and acetone, and dried in vacuo to give the title compound as a light-brown solid (14.74 g, 98percent yield). ?HNMR(DMSO-d6, 400 MHz) 11.38 (br, 1H), 11.10 (br, 1H), 10.46 (s, 1H), 6.53 (s, 1H), 6.18 (s, 1H), MS m/z 152.43 [M+1].

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it, 873-83-6, 6-Aminopyrimidine-2,4(1H,3H)-dione.

Reference:
Patent; DANA-FARBER CANCER INSTITUTE, INC.; GRAY, Nathanael, S.; HATCHER, John; CHOI, Hwan, Geun; (198 pag.)WO2016/130920; (2016); A2;,
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.18740-38-0, name is Thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, molecular formula is C6H4N2O2S, molecular weight is 168.1732, as common compound, the synthetic route is as follows.Recommanded Product: Thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

3 g (0.018 mol) of the intermediate lib was placed in a 100 mL three-necked flask,30 mL (0.329 mol) of phosphorus oxychloride was slowly added dropwise,After 30 min addition, 2 drops of DMF were added to the reaction mixture and the reaction was heated to reflux for 8 h. The reaction was poured into 1000 g of ice water with stirring, and a large amount of orange-colored solid was precipitated. The filter cake was washed with a large amount of water and dried at 45 C for 24 hours to obtain 1.8 g of an orange solid in a yield of 49%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,18740-38-0, Thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, and friends who are interested can also refer to it.

Reference:
Patent; Jiangxi science and technology Normal University; Zhu, wufu; Zheng, PengWu; Chen, Chen; Xu, Yuan; Sun, chengyu; Wu, Chunjiang; Tu, Qidong; (22 pag.)CN103980287; (2016); B;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 24415-66-5, 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 24415-66-5 as follows.

The preparation method of the compound e30 comprises the steps of: taking about 1 mmol of 7-chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine and about 3 mmol.6-Methyl-1H-indole was added to a 10 mL microwave reaction tube.Further, 2 mL of hexafluoroisopropanol solvent and about 0.1 mmol of bistrifluoromethanesulfonimide catalyst were added, sealed and heated to 100 C with stirring and reacted for about 6 h.Then, the reaction system was monitored by TLC, and after the reaction system was cooled to room temperature, it was separated and purified by column chromatography to obtain pure compound e30.The compound e30 is a yellow solid with a yield of 63%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,24415-66-5, its application will become more common.

Reference:
Patent; Zhengzhou University; Liu Hongmin; Yu Bin; Zheng Yichao; Yuan Shuo; Shen Dandan; (27 pag.)CN109020976; (2018); A;,
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.32779-36-5, name is 5-Bromo-2-chloropyrimidine, molecular formula is C4H2BrClN2, molecular weight is 193.4291, as common compound, the synthetic route is as follows.Recommanded Product: 32779-36-5

Reference example 77; (1); To 5-bromo-2-chloropyrimidine 2.90g, 1-tert-butoxycarbonylpiperazine 4.19g in 1,4-dioxane 70ml was added potassium carbonate 3.73g, and the mixture was stirred under reflux for 1.5 hours. Thereto was added water and the mixture was extracted with diethyl ether twice. The combined organic layer was dried and the solvent was removed and purified with silica gel column chromatography (hexane:ethyl acetate=15:1?8:1) to give compound (2) (5.09g) as a colorless solid. APCI-MS (m/e): 343/345 (M+H)+

At the same time, in my other blogs, there are other synthetic methods of this type of compound,32779-36-5, 5-Bromo-2-chloropyrimidine, and friends who are interested can also refer to it.

Reference:
Patent; Mitsubishi Tanabe Pharma Corporation; EP1956009; (2008); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia