Category: 5018-38-2

Angst, Daniela; Gessier, Francois; Janser, Philipp; Vulpetti, Anna; Walchli, Rudolf; Beerli, Christian; Littlewood-Evans, Amanda; Dawson, Janet; Nuesslein-Hildesheim, Barbara; Wieczorek, Grazyna; Gutmann, Sascha; Scheufler, Clemens; Hinniger, Alexandra; Zimmerlin, Alfred; Funhoff, Enrico G.; Pulz, Robert; Cenni, Bruno published the artcile< Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase>, Synthetic Route of 5018-38-2, the main research area is LOU064 remibrutinib Bruton tyrosine kinase inhibitor autoimmune diseases antiinflammatory.

Bruton’s tyrosine kinase (BTK), a cytoplasmic tyrosine kinase, plays a central role in immunity and is considered an attractive target for treating autoimmune diseases. The use of currently marketed covalent BTK inhibitors is limited to oncol. indications based on their suboptimal kinase selectivity. We describe the discovery and preclin. profile of LOU064 (remibrutinib, 25), a potent, highly selective covalent BTK inhibitor. LOU064 exhibits an exquisite kinase selectivity due to binding to an inactive conformation of BTK and has the potential for a best-in-class covalent BTK inhibitor for the treatment of autoimmune diseases. It demonstrates potent in vivo target occupancy with an EC90 of 1.6 mg/kg and dose-dependent efficacy in rat collagen-induced arthritis. LOU064 is currently being tested in phase 2 clin. studies for chronic spontaneous urticaria and Sjoegren’s syndrome.

Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Synthetic Route of 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Beck, Hartmut; Jeske, Mario; Thede, Kai; Stoll, Friederike; Flamme, Ingo; Akbaba, Metin; Ergueden, Jens-Kerim; Karig, Gunter; Keldenich, Joerg; Oehme, Felix; Militzer, Hans-Christian; Hartung, Ingo V.; Thuss, Uwe published the artcile< Discovery of Molidustat (BAY 85-3934): A Small-Molecule Oral HIF-Prolyl Hydroxylase (HIF-PH) Inhibitor for the Treatment of Renal Anemia>, HPLC of Formula: 5018-38-2, the main research area is diheteroaryldihydropyrazolone preparation HIF prolyl hydroxylase inhibitor kidney disease anemia; molidustat BAY3934 preparation HIF prolyl hydroxylase inhibitor kidney anemia; BAY 85-3934; HIF-PH; inhibitors; metalloenzymes; molidustat.

Small-mol. inhibitors of hypoxia-inducible factor prolyl hydroxylases (HIF-PHs) are currently under clin. development as novel treatment options for chronic kidney disease (CKD) associated anemia. Inhibition of HIF-PH mimics hypoxia and leads to increased erythropoietin (EPO) expression and subsequently increased erythropoiesis. Herein the authors describe the discovery, synthesis, structure-activity relationship (SAR), and proposed binding mode of novel 2,4-diheteroaryl-1,2-dihydro-3H-pyrazol-3-ones as orally bioavailable HIF-PH inhibitors for the treatment of anemia. High-throughput screening of the authors’ corporate compound library identified BAY-908 as a promising hit. The lead optimization program then resulted in the identification of molidustat (BAY 85-3934), a novel small-mol. oral HIF-PH inhibitor. Molidustat is currently being investigated in clin. phase III trials as molidustat sodium for the treatment of anemia in patients with CKD.

ChemMedChem published new progress about Anemia (chronic kidney disease associated). 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, HPLC of Formula: 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Fun, Hoong-Kun; Yeap, Chin Sing; Chidan Kumar, C. S.; Yathirajan, H. S.; Siddegowda, M. S. published the artcile< 4,6-Dichloro-5-methoxypyrimidine>, SDS of cas: 5018-38-2, the main research area is crystal structure dichloromethoxypyrimidine; mol structure chloromethoxypyrimidine; pyrimidine dichloromethoxy crystal mol structure.

The mol. of 4,6-dichloro-5-methoxypyrimidine, C5H4Cl2N2O, is close to being planar (root-mean-square deviation = 0.013 Å), apart from the C atom of the methoxy group, which deviates by 1.082(2) Å from the mean plane of the other atoms. In the crystal, short Cl···N contacts [3.0940(15) and 3.1006(17) Å] generate a 3-dimensional framework. Crystallog. data are given.

Acta Crystallographica, Section E: Structure Reports Online published new progress about Crystal structure. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, SDS of cas: 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

La Colla, Paolo; Marcialis, Maria A.; Flore, Ornella; Sau, Mario; Garzia, Aldo; Loddo, Bernardo published the artcile< Specific inhibition of virus multiplication by bichlorinated pyrimidines>, COA of Formula: C5H4Cl2N2O, the main research area is antiviral dichloro pyrimidine derivative; viricidal dichloropyrimidine derivative.

None of the 13 nonchlorinated or monochlorinated pyrimidines tested had any inhibitory effect on polio 1, vaccinia, and herpes simplex viruses, but all 8 dichloro derivatives inhibited growth of all 3 viruses, with 2-amino-4,6-dichloropyrimidine (I) [56-05-3] being the most active. 2-Mercaptoethanol enhanced the antiviral effect of the dichloropyrimidines. The compounds also inhibited coxsackie B1 virus, but had no effect on vesicular stomatitis or Newcastle disease viruses. Results from the effect of protein and RNA precursors on the antipolio action of I and from the effects of I on poliovirus synthesis and organization are also given. The mechanism of action of I and the structure-activity relation for the dichloropyrimidines are discussed.

Annals of the New York Academy of Sciences published new progress about Antiviral agents. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, COA of Formula: C5H4Cl2N2O.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 5018-38-2, 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. 5018-38-2, name is 4,6-Dichloro-5-methoxypyrimidine, molecular formula is C5H4Cl2N2O, 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 3.4 Preparation of 4-(6-Chloro-5-methoxy-pyrimidin-4-yloxy)-piperidine-1-carboxylic Acid Isopropyl Ester A solution of 4-hydroxy-piperidine-1-carboxylic acid isopropyl ester (71.0 g, 380 mmol) and 4,6-dichloro-5-methoxypyrimidine (71.6 g, 400 mmol) in anhydrous THF (1 L) was cooled to 5 C. under N2. A solution of potassium t-butoxide (1.0 M in THF, 380 mL, 380 mmol) was added dropwise over 1 h. The reaction temperature was kept under 10 C. during addition. The reaction mixture was stirred at 5-10 C. for 1 h, quenched with saturated NH4Cl (200 mL), and diluted with ether (1 L) and water (1 L). The aqueous phase was separated and discarded. The organic extract was washed with brine (800 mL), dried over MgSO4, and then concentrated. The residue was dissolved in hexane (400 mL) and filtered over Celite to remove a small amount of brown solid. The solvent was removed from the filtrate to afford a pale amber oil which gradually crystallized to give the title compound (130 g, 98.6% yield) as a pale amber solid. Exact Mass calculated for C14H20ClN3O4: 329.1. Found: LCMS m/z=330.2 (M+H+); 1H NMR (400 MHz, CDCl3) delta 1.25 (d, J=6.2 Hz, 6H), 1.82 (m, 2H), 2.02 (m, 2H), 3.40 (m, 2H), 3.80 (m, 2H), 3.91 (s, 3H), 4.95 (m, 1H), 5.39 (m, 1H), 8.27 (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 5018-38-2, 4,6-Dichloro-5-methoxypyrimidine.

Reference:
Patent; ARENA PHARMACEUTICALS, INC.; US2009/286816; (2009); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of 5018-38-2, 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 5018-38-2 as follows.

4-(5-Methoxy-4-pyrimidinyl)-2-methylpiperazine Method 2 A solution of 2-methylpiperazine (20 g) in water (100 mL) was reacted with solid 4,6-dichloro-5-methoxypyrimidine (5.00 g, 27.9 mmole) in a procedure similar to that given for Method 2 of Example 14. After hydrogenation and filtration of the catalyst, the product was extracted from the filtrate with CH2 Cl2. The extracts were concentrated in vacuo, and the residue was Kugelrohr distilled to give a clear oil (5.46 g, 99.8%). The oil was dissolved in acetonitrile and concentrated HCl added to form the salt which was recrystallized from i-PrOH and dried in vacuo to give the product as a white powder (4.02 g, m.p. 185-188 C.).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,5018-38-2, its application will become more common.

Reference:
Patent; Bristol-Myers Squibb Company; US5434154; (1995); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 5018-38-2, Adding some certain compound to certain chemical reactions, such as: 5018-38-2, name is 4,6-Dichloro-5-methoxypyrimidine,molecular formula is C5H4Cl2N2O, 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 5018-38-2.

To a solution of 4,6-dichloro-5-methoxypyrimidine (20.00 g, 1 12 mmol) in DCE (250 mL) at 0 C was added aluminum trichloride (22.35 g, 168 mmol) in two portions. The reaction mixture was stirred at 0 C for 10 min, then at 50 C for 4 hr. The mixture was cooled to 0 C and aqueous HCI (1 M, 120 mL) followed by MeOH (50 mL) were added slowly while stirring vigorously. The mixture was poured into water and extracted with Et20 (3x). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated. The residue was dried in vacuum to afford INT 15 as a beige solid. UPLC-MS: MS (ESI): [M-H]” 163.0, rt = 0.44 min. 1 H NMR (DMSO-d6): delta (ppm) 1 1 .69 (s, br, 1 H), 8.38 (s, 1 H).

According to the analysis of related databases, 5018-38-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; NOVARTIS AG; BRIARD, Emmanuelle; AUBERSON, Yves; CENNI, Bruno; PULZ, Robert Alexander; ANGST, Daniela; (62 pag.)WO2016/79669; (2016); 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. 5018-38-2, name is 4,6-Dichloro-5-methoxypyrimidine. This compound has unique chemical properties. The synthetic route is as follows. Recommanded Product: 5018-38-2

1-(5-Methoxy-4-pyrimidinyl)piperazine Piperazine (20 g) was dissolved in water (100 mL) in a Parr bottle and then solid 4,6-dichloro-5-methoxypyrimidine (5.00 g, 27.9 mmole) was added. The mixture was vigorously stirred for 2 h at room temperature during which the 4,6-dichloro-5-methoxypyrimidine dissolved. The stirring bar was removed, catalyst (10% Pd/C, 1.0 g) was added to the turbid solution, and the mixture was then hydrogenated (60 psi, 3 h) at room temperature. The catalyst was filtered off and the filtrate extracted 3 times with CH2 Cl2. The CH2 Cl2 extracts were dried over Na2 SO4 and concentrated in vacuo to give a clear oil which solidified upon standing (3.34 g, 61.7%). This crude product was Kugelrohr distilled (yield 3.24 g), dissolved in acetonitrile, and concentrated HCl was added to precipitate the product as a white powder which was dried in vacuo (4.32 g, 94.0% from crude product, m.p. 219-221.5 C.).

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, 5018-38-2, 4,6-Dichloro-5-methoxypyrimidine.

Reference:
Patent; Bristol-Myers Squibb Company; US5300506; (1994); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

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. 5018-38-2, name is 4,6-Dichloro-5-methoxypyrimidine. A new synthetic method of this compound is introduced below., Application In Synthesis of 4,6-Dichloro-5-methoxypyrimidine

A 500 ml, 4-necked flask equipped with thermometer, mechanical stirrer and condenser with gas inlet was purged with N2 and charged with NaH (4.4 g; 0.1 1 mol) and N,N-dimethylformamide (50 ml). In a separate flask were dissolved 4-hydroxy-piperidine-1-carboxylic acid isopropyl ester (18.7 g; 0.1 mol) and 4,6-dichloro-5-methoxy-pyrimidine (17.9 g; 0.1 mol) in DMF (50 ml; 0.5 L/mol). The prepared solution was then added dropwise to the above- mentioned NaH/DMF suspension while maintaining the temperature between – 10 and -5C. The resulting mixture is then stirred for one hour, then allowed to warm up to room temperature and stirred for 17 hours. Water (300 ml; 3 L/mol) was added dropwise while maintaining the temperature between 15-300C by cooling with tap water. Heptane (125 ml; 1.25 L/mol) was added and the resulting mixture was heated up to 55C. The aqueous layer was discarded; the organic layer was cooled down to 200C and stirred for another 3-2Oh. The resulting precipitate was filtered and dried in vacuum (at) 500C for 2Oh to yield the title compound as a residue.

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, 5018-38-2, 4,6-Dichloro-5-methoxypyrimidine.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; WELLS, Kenneth M.; FECH, Gary; WU, Wenju; FAWZY, Nagy E.; WO2010/135505; (2010); A2;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 5018-38-2, 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. 5018-38-2, name is 4,6-Dichloro-5-methoxypyrimidine, molecular formula is C5H4Cl2N2O, 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 3: Preparation of 6-chloro-N-[2-[2-fluoro-4-[[4-(trifluoromethyl)-2-pyridyl] oxy]phenyl]ethyl]-5-methoxy-pyrimidin-4-amine (V-14) To a solution of 2-[2-fluoro-4-[[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]ethanamine hydrochloride (344 mg, 0.9 mmol) in NMP (5 ml.) was added diisopropylethylamine (0.36 mL, 2.1 mmol). The solution was stirred for 5 min at room temperature at which time 4,6-dichloro-5-methoxypyrimidine (150 mg, 0.8 mmol) was added. The reaction mixture was stirred at 80C overnight then allowed to cool to room temperature. Water was added and was extracted with MTBE (3x). The combined organic layers were washed with water, dried over Na2S04, and concentrated in vacuo. The residue was purified by flash silica column chromatography to provide 288 mg (0.65 mmol, 78%) of the light yellow oily 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 5018-38-2, 4,6-Dichloro-5-methoxypyrimidine.

Reference:
Patent; BASF SE; BASF SCHWEIZ AG; GRAMMENOS, Wassilios; CRAIG, Ian, Robert; BOUDET, Nadege; MUeLLER, Bernd; DIETZ, Jochen; LAUTERWASSER, Erica, May, Wilson; LOHMANN, Jan, Klaas; MONTAG, Jurith; WO2013/113720; (2013); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia