Category: pyrimidines

Synthetic Route of 149849-94-5, Adding some certain compound to certain chemical reactions, such as: 149849-94-5, name is Methyl 2-chloropyrimidine-4-carboxylate,molecular formula is C6H5ClN2O2, 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 149849-94-5.

A 100 mL three neck flask was charged with NaH (55%, 130 mg) and tetrahydrofuran (2 mL). At 5 C tetraethyleneglycol monomethylether (530 mg) dissolved in tetrahydrofuran (2 mL) was added dropwise and the mixture was stirred for 1 hour at 5 C. A solution of methyl 2-chloropyrimidine-4- carboxylate (390 mg) in tetrahydrofuran (4 mL) was added at 5 C and stirring was continued at ambient temperature for 2 hours. Tetrahydrofuran and water were added (10:1 , 10 mL), and the mixture extracted three times with dichloromethane. The combined organic layers washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by chromatography using an ISCO CombiFlash Companion MPLC (12 g RediSep Gold column, eluting with 0-50%dichloromethane/methanol) followed by treatment with -pentane, filtration, concentration and purification by ISCO CombiFlash Companion MPLC (15 g Chromabond RP-C18 column, eluting with 0-100% water/methanol) gave the title compound. MS (APCI) m/z 344.2 (M+H)+.

According to the analysis of related databases, 149849-94-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ABBVIE INC.; ABBVIE DEUTSCHLAND GMBH & CO. KG; BRAJE, Wilfried; DOHERTY, George; JANTOS, Katja; JI, Cheng; JUDD, Andrew; KUNZER, Aaron; MASTRACCHIO, Anthony; SONG, Xiaohong; SOUERS, Andrew; SULLIVAN, Gerard; TAO, Zhi-Fu; LAI, Chunqui; KLING, Andreas; POHLKI, Frauke; TESKE, Jessc; WENDT, Michael; BRADY, Patrick; WANG, Xilu; PENNING, Thomas; MICHAELIDES, Michael; (448 pag.)WO2019/35927; (2019); A1;,
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Reference 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.

A kind of the improved 4, 6 – dichloro pyrimidine production process, characterized in that the production process comprises the following steps: (1) to the reaction kettle top feed port input 1 parts by weight of 4, 6 – dihydroxy pyrimidine and 3 parts by weight of chloroform, opening the stirrer stirring, continue adding 0.5 parts by weight of pyridine catalyst, and then open the jacket steam make the reaction kettle temperature to rise to 50 C, from the reactor into the bottom of the 1 parts by weight of phosgene to the phosgenation reaction, after the reaction is complete, to inject the nitrogen in the reactor catches up with was mad, at the same time the exhaust gas by the pipe into the absorption tower; (2) to be step 1 the product in the transfer to the rectifying tower, control rectification temperature is 65 C, collecting chloroform fraction, to be its after cooling to room temperature, the filling storage recycling; (3) collecting the step 2 in the remaining product, transferred to ice in the ice solution, slowly dropping concentration is 10% hydrochloric acid to adjust the pH of the solution to 5, standing the solution is layered, then methyl tert-butyl ether to the organic phase extraction, extraction 3 – 4 times, saturated copper sulfate solution for washing, until the copper sulfate solution is not color-changing, collecting pyridine circulation use; (4) the step 3 in the remaining product to filter, washing, and drying to obtain the target product 4, 6 – dichloro pyrimidine.The beneficial effects of the present invention: 1) using phosgene to replace the traditional process of phosphorus oxychloride, to avoid the emergence of phosphorus-containing by-product, the protection of the environment; 2) by adding pyridine catalyst, can accelerate the reaction of generating; 3) traditional use phosphorus oxychloride with 4, 6 – dihydroxy pyrimidine chloride obtained when the 4, 6 – two chlorine pyrimidine, easy to produce 3 different by-product, so that the trouble in processing after, and the yield of target product is not high, in the reaction of the present invention less by-products, and the yield of 4, 6 – dichloro pyrimidine higher; 4) by adjusting the solution pH, methyl tert-butyl ether extraction, and sulfuric acid copper and washing the collecting various pyridine, avoiding the traditional rectification, and steaming and method and the like caused by the leakage of pyridine, ensures the safety of the operators.

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

Reference:
Patent; Anhui Guangxin Agrochemical Co., Ltd; Huang, Jinxiang; Guo, Xuejun; wu, Jianping; hu, minghong; tang, Xiude; cheng, Weijia; li, Hongwei; Xu, Xiaobing; Yang, Zhiwei; Gao, yanbing; (4 pag.)CN106187913; (2016); A;,
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Electric Literature of 4318-56-3, 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. 4318-56-3, name is 6-Chloro-3-methylpyrimidine-2,4(1H,3H)-dione, molecular formula is C5H5ClN2O2, 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 mixture containing 10.0 g (62.28 mmol) of 6- chloro-3-methyluracil in 200 ml of ethanol was added 13.70 ml (436.50 mmol) of hydrazine. The mixture was heated to 75C under a nitrogen atmosphere overnight. The solids were filtered, washed with ethanol and dried to afford 9.70 g (99.74%) of product as a pale yellow solid. ¹H NMR (CDC13) No.: 3. 02 (s, 3H), 4.78 (s, 1H), 6.28 (bs, 4H) MS Calcd.: 156; Found: 155 (M-H).

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 4318-56-3, 6-Chloro-3-methylpyrimidine-2,4(1H,3H)-dione.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; WO2005/99688; (2005); A2;,
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Electric Literature of 1820-81-1, 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 1820-81-1 as follows.

General procedure: To a solution of Thy (37 mg, 0.3 mmol), 7-MeGuo hydroiodide (191 mg, 0.45 mmol) and potassium dihydrophosphate (KH2PO4, 20 mg, 0.15 mmol) in 50mM Tris-HCl buffer, pH 7.5, 80 mL) at ambient temperature, 5 muL of 32 mg/mL E. coli purine nucleoside phosphorylase (PNP) solution (1.48 U) and 12.5 muL E. coli uridine phosphorylase (UP) (8.60 U) were added in one portion. The reaction mixture was allowed to stand for 5 h at ambient temperature under neat stirring and then allowed to stand for 15 h at ambient temperature without stirring. The conversion of the initial 7-MeGuo was controlled by HPLC. The reaction mixture was cooled to 0 C and then filtered through nitrocellulose membrane Whatman (0.2 mum, 25 mm) to remove the white precipitate of 7-methylguanine (7-MeGua). The precipitate was washed with milli-Q water (15 mL). The combined transparent filtrate was concentrated under reduced pressure using a rotary evaporator to ca. 2 mL (bath temperature (5 mL) was then added to the suspension. The resulting mixture was concentrated to near dryness and co-evaporated with ethanol (2×20 mL). The dry residue was applied on a chromatographic column (diameter 20 mm) with silica gel (20 mL) for purification. For the protection, the silica gel layer was topped with ca 0.5-cm layer of sand. The column was washed with dichloromethane (25 mL), a mixture of dichloromethane and ethanol (95:5, v/v, 50 mL), and a mixture of dichloromethane and ethanol (90:10, v/v, 100 mL). The product was eluted with dichloromethane: ethanol (80:20, v/v, 100 mL) and 10 mL fractions were collected and evaporated in vacuo to dryness. The residue was co-evaporated 5 times with dichloromethane and dried using a vacuum pump at r.t. for 1 h.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1820-81-1, its application will become more common.

Reference:
Article; Alexeev, Cyril S.; Drenichev, Mikhail S.; Dorinova, Evgeniya O.; Esipov, Roman S.; Kulikova, Irina V.; Mikhailov, Sergey N.; Biochimica et Biophysica Acta – Proteins and Proteomics; vol. 1868; 1; (2020);,
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Electric Literature of 22536-65-8 , The common heterocyclic compound, 22536-65-8, name is 2-Chloro-5-methoxypyrimidine, molecular formula is C5H5ClN2O, 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.

A) 5-methoxypyrimidine-2-carbonitrile To a solution of 2-chloro-5-methoxypyrimidine (4.4 g) and 1,4-diazabicyclo[2.2.2]octane (6.7 g) in a mixed solvent of dimethyl sulfoxide (114 mL) and water (18 mL) was added potassium cyanide (4.00 g). The reaction mixture was stirred at 70°C for 5 hr, water was added thereto, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over sodium sulfate, and the solvent was evaporated under reduced pressure to give the title compound (3.5 g). 1H NMR (400 MHz, CDCl3) delta 4.02 (3H, s), 8.47 (2H, s).

The synthetic route of 22536-65-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Pharmaceutical Company Limited; MIKAMI, Satoshi; NAKAMURA, Shinji; ASHIZAWA, Tomoko; SASAKI, Shigekazu; TANIGUCHI, Takahiko; NOMURA, Izumi; KAWASAKI, Masanori; EP2848618; (2015); A1;,
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Related Products of 4595-59-9, 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.

General procedure: Forthe Suzuki-Miyaura reaction, a 50 mL round-bottomed flask was charged with aryl halide(0.5 mmol), arylboronic acid (0.65 mmol), K2CO3 (1 mmol), catalyst (0.002 g; 0.0005 mmol ofPd) and water (4 mL) and stirred at appropriate temperature. The progress of the reaction wasmonitored by thin layer chromatography using aluminum coated TLC plates (Merck) underUV light. At the end of reaction, the mixture was cooled down to room temperature and theproduct diluted with water (10 mL) and extracted with ether (3 x 15 mL). The combinedextract was washed with brine (3 x 15 mL) and dried over Na2SO4. After evaporation of the solventunder reduced pressure, the residue was subjected to column chromatography with ethylacetate/hexane (1:9) as eluent to get the desired product.

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 4595-59-9, 5-Bromopyrimidine.

Reference:
Article; Hazarika, Munmi; Borah, Debajit; Bora, Popymita; Silva, Ana R.; Das, Pankaj; PLoS ONE; vol. 12; 9; (2017);,
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Adding a certain compound to certain chemical reactions, such as: 32779-36-5, 5-Bromo-2-chloropyrimidine, 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, Computed Properties of C4H2BrClN2, blongs to pyrimidines compound. Computed Properties of C4H2BrClN2

To a solution of THF (2000.0 ml) and sodium hydride (17.0 gm, 0.708 mol), was added A/-5-(4-bromophenyl)-6-(-2-hydroxyethoxy)-4-pyrimidinyl-//- propylsulfamide (100.0 gm, 0.23 mol) at 25-30°C. Stirred the content for 30 min at 25-30° C. DMF (400.0 ml) and 5-bromo-2-chloro-pyrimidine (65.0 gm; 0.033 mol) was added to the reaction mass at 25-30° C. Stirred and heated reaction mass to 60-65°C and maintain the reaction mass at 60-65° C for 2-4 hr. After completion of reaction monitored by HPLC, cooled the reaction mass to 25-30° C and 5percent w/v citric acid solution (2500.0 ml) was added. The compound was extracted twice with ethyl acetate (1500.0 ml x 2), followed by organic layer was washed with 10percent w/v brine solution (1500.0 ml). Ethyl acetate layer was concentrated at 55-60°C under reduced pressure to produce A/-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy] ethoxy]-4-pyrimidinyl]-/V-propylsulfamide as a crude residue. Obtained residue was dissolved at 65-70°C in methanol (2400.0 ml), stirred and maintained for 30 min. The resulting solution was gradually cooled to room temperature then cooled to 0-5°C and maintained reaction mass at 0-5°C for 45-60 min. Obtained solid was filtered, washed with methanol (100.0 ml), suck dried to afford crude /V-[5-(4-bromophenyl)-6-[2-[(5-bromo-2- pyrimidinyl)oxy] ethoxyJ^-pyrimidinylJ-Af-propylsulfamide [Macitentan]. [Yield = 121.5 gm; Purity (HPLC) = 99.68percent]. Purification of Macitentan ( I ) Macitentan crude (121.5 gm, 0.202 mol) wet solid was dissolved at 65-70°C in methanol (2400.0 ml) and decolorized with activated charcoal. The resulting solution was gradually cooled to room temperature then cooled to 0- 5°C and maintained for 45-60 min. Obtained solid was filtered, washed with methanol (100.0 ml), suck dried and dried under vacuum at 55-60°C to afford highly pure Macitentan. [Yield = 111.5 gm; Purity (HPLC) = 99.94percent]. (M + H)+/z= 589.0. 1H NMR (CDCIa): delta 8.49 (s, 2 H), 8.45 (s, 1H), 7.57-7.54 (m, 2H), 7.16-7.12 (m, 2H), 6.87 (s, 1 H), 5.60-5.57 (t, J = 6.24 Hz, 1 H), 4.71- 4.69 (m, 2H), 4.61-4.59 (m, 2H), 2.97-2.92 (q, 2H), 1.61-1.52 (h, J = 7.36 Hz, 2H), 0.94-0.91 (t, J = 7.36 Hz, 3H). 13C NMR (CDC ): delta 11.24, 21.97, 44.62, 64.68, 65.48, 104.80, 111.85, 121.31, 129.48, 131.35, 132.51 , 155.82, 156.41 , 159.68, 163.10, 165.75.

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; MEGAFINE PHARMA (P) LTD.; MATHAD Vijayavitthal Thippannachar; NIPHADE NAVNATH CHINTAMAN; KABRA SANJAY RAMESHWAR; JAGTAP KUNAL MADHAV; PAWAR ANIL RAMBHAU; (43 pag.)WO2016/203489; (2016); A1;,
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Reference of 1088994-22-2, 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. 1088994-22-2, name is 5-Methyl-2-(pyrimidin-2-yl)benzoicacid, molecular formula is C12H10N2O2, 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.

Example 62:Compound 13: (S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiror2.51octan-6- yl)(5-methyl-2-(pyrimidin-2-yl)phenyl)methanone (Isomer A) HPLC retention time: 9 min (150 mg)Alternatively Compound 13 was obtained by the following procedure: 5-methyl-2- (pyrimidin-2-yl)benzoic acid (428mg, 2mmol; prepared according to WO 2008147518), intermediate 34 (500mg, 2mmol) and DIPEA (0.65ml) were dissolved in DCM (5ml) at 0 C, then T3P (50% in DCM, 1.5g) was added. The mixture is stirred at reflux for 8 hours then at RT overnight. The reaction was washed with NaOH 1 M and water, dried (Na2SO4) and evaporated. The crude was purified by silica gel column chromatography (DCM to DCIWMeOH = 95/05). 180mg of the desired compound were isolated.MS (ESI); m/z 446 [MH]+1HNMR [the product is present as a mixture of conformers. The assignment refers to the major component] (CDCI3) d ppm 8.80-8.77 (m, 1 H) 8.64-8.6 (d, 1 H) 8.36- 8.31 (d, 1 H) 8.08-8.04 (m, 1 H) 7.43-7.17 (m, 3H) 7.08-7.03 (t,1 H) 6.36-6.31 (d, 1 H) 5.79 (bs, 1 H) 5.19-5.1 1 (m, 1 H) 4.00-3.89 (m, 1 H) 3.71 -3.62 (m, 1 H) 3.50-3.39 (m, 1 H) 3.37-3.21 (m, 1 H) 2.45 (s, 3H) 2.31 -2.24 (dd, 1 H) 1.99-1.88 (dt, 1 H) 1.25- 1.19 (d, 1 H) 0.75-0.68 (d, 1 H) 0.60-0.13 (m, 4H).

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 1088994-22-2, 5-Methyl-2-(pyrimidin-2-yl)benzoicacid.

Reference:
Patent; ROTTAPHARM S.P.A.; STASI, Luigi, Piero; ROVATI, Lucio; WO2011/6960; (2011); A1;,
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Electric Literature 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.

Intermediate U1: tert-butyl 4-(2-{1-[(6-amino-5-cyanopyrimidin-4-yl)amino]ethyl}indolizin-3-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate To a solution of tert-butyl 4-[2-(1-aminoethyl)indolizin-3-yl]-1,2,3,6-tetrahydropyridine-1-carboxylate Q7 (0.039 g, 0.11 mmol) in t-BuOH (1.5 mL), 4-amino-6-chloropyrimidine-5-carbonitrile (0.017 g, 0.11 mmol) was added followed by DIPEA (0.038 mL, 0.22 mmol) and the resulting mixture was heated to reflux for 3 h. The solvent was removed and the crude was partitioned between DCM/MeOH?4/1 and water; the organic phase was dried over sodium sulfate, the solvent was removed under reduced pressure and the crude was purified by flash chromatography on Biotage silica-NH SNAP cartridge (cyclohexane to cyclohexane_AcOEt=50:50) to afford title compound as a yellow oil (0.045 g, 0.098 mmol, 89% yield). MS/ESI+ 460.4 [MH]+, Rt=1.14 min (Method A).

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. 60025-09-4, 4-Amino-6-chloropyrimidine-5-carbonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; CHIESI FARMACEUTICI S.P.A.; BIAGETTI, Matteo; ACCETTA, Alessandro; CAPELLI, Anna Maria; GUALA, Matilde; RETINI, Michele; US2015/361100; (2015); A1;,
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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. 62968-37-0, name is 4-(2-Chloropyrimidin-4-yl)morpholine. This compound has unique chemical properties. The synthetic route is as follows. COA of Formula: C8H10ClN3O

General procedure: To a solution of 32 were added 2-chloropyrimidine intermediate (3a-3e, 3g) (1 equiv) and catalytic amount of 1N HCl in AcOH. The reaction mixture and a magnetic bar were sealed in the reaction vessel of an Anton paar monowave 300 and irradiated for 2 h at 160 C. The reaction mixture was concentrated in vacuo and then diluted with H2O or saturated aqueous NaHCO3. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over MgSO4 and then concentrated in vacuo. The residue was purified by flash column chromatography on silica gel.

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, 62968-37-0, 4-(2-Chloropyrimidin-4-yl)morpholine.

Reference:
Article; Jo, Jeyun; Kim, Sou Hyun; Kim, Heegyu; Jeong, Myeonggyo; Kwak, Jae-Hwan; Taek Han, Young; Jeong, Jee-Yeong; Jung, Young-Suk; Yun, Hwayoung; Bioorganic and Medicinal Chemistry Letters; vol. 29; 1; (2019); p. 62 – 65;,
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