Pyrimidines

Reference of 10244-24-3 , The common heterocyclic compound, 10244-24-3, name is 4,4′-(6-Chloropyrimidine-2,4-diyl)dimorpholine, molecular formula is C12H17ClN4O2, 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 4 Preparation of Buparlisib (0036) Added compound 6 (14.4 g, 0.06 mol), bis(pinacolato)diboron (compound 5) (18.2 g, 0.072 mol), DMSO (200 mL), KOAc (17.64 g, 0.18 mol) and PdCl2(PPh3)2 (4.2 g, 0.006 mol) into a second reactor, then heated the resulting mixture to 5 C. and kept the reaction for 7 hours, and then added compound 4 (17 g, 0.06 mol) into the second reactor, kept the reaction for 16 hours. Put the reaction solution into water after the reaction was finished, and large amount of solid were separated. The resulting mixture was filtered, stirred with methanol/acetone (V:V=1:1) and crystallized for 3 hours. The filter cake was dried in vacuo at 60 C. for 8 hours to obtain the buparlisib product (compound 1) as a white solid (23.15 g, yield 94%), HPLC purity: 99.2%. Mass Spectrum: M+H- 411.

The synthetic route of 10244-24-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; XU, YONG; (6 pag.)US2016/264546; (2016); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of 62802-38-4, 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.62802-38-4, name is 5-Bromo-2-fluoropyrimidine, molecular formula is C4H2BrFN2, molecular weight is 176.9745, as common compound, the synthetic route is as follows.

To a solution of 5-ethyl-4-nitro-1H-pyrazole (350 mg, 2.5 mmol) and 3,4- dihydro-2H-pyran (319 mg, 3.8 mmol) in DCM (20 mE) at 0 C was addedp-TsOH(43 mg, 0.25 mmol), and the mixture was stirred at 0 C for lh and then at rt overnight. DCM (100 mL) was added, and the mixture was washed with water and brine, dried over Na2 SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with petroleum ether/EtOAc (10:1 to 1:1) to afford a mixture of 3-ethyl-4-nitro-1- (tetrahydro-2H-pyran-2-yl)- 1JJ-pyrazole and 5 -ethyl-4-nitro- 1 -(tetrahydro-2H-pyran-2-yl)- 1H- pyrazole.; To a solution of 3-ethyl-4-nitro-1-(tetrahydro-2H-pyran-2-yl)-1JJ-pyrazole and5-ethyl-4-nitro-1-(tetrahydro-2H-pyran-2-yl)-1ff-pyrazole (557 mg, 2.5 mmol) in MeOH (20 mE) at 0C was added 10 % Pd/C (50 mg), and the mixture was stirred under H2 overnight at rt. DCM (20 mE) was added and the mixture was filtered through the Celite. The filtrate was concentrated under reduced pressure to afford a mixture of 3-ethyl-1-(tetrahydro-2H-pyran-2- yl)- 1H-pyrazol-4-amine and 5-ethyl-i -(tetrahydro-2H-pyran-2-yl)- 1H-pyrazol-4-amine, which was used in the next step without further purification; To a solution of 3-ethyl-1-(tetrahydro-2H-pyran-2-yl)-iH-pyrazol-4-amine, – ethyl-1-(tetrahydro-2J1-pyran-2-yl)-1H-pyrazol-4-amine (252 mg, 1.03 mmol) and 5-bromo-2- fluoro-pyrimidine (166 mg, 0.94 mmol) in DMSO (7 mL) was added DIEA (243 mg, 1.88 mmol), and the mixture was stirred at 100 C for 1.5 h. DCM (100 mE) was added, and the mixture was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with petroleum ether EtOAc (10:1 to 2:1) to afford a mixture of 5-bromo-N-(3 -ethyl-i -(tetrahydro-2H-pyran-2-yl)- 1H-pyrazol-4-yl)pyrimidin-2-amine and 5-bromo-N-(5-ethyl- i -(tetrahydro-2H-pyran-2-yl)- 1H- pyrazol-4-yl)pyrimidin-2-amine.

The chemical industry reduces the impact on the environment during synthesis 62802-38-4, I believe this compound will play a more active role in future production and life.

Reference:
Patent; PLEXXIKON INC.; HOLLADAY, Mark W.; LIU, Gang; (267 pag.)WO2017/19804; (2017); A2;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 1193-24-4 ,Some common heterocyclic compound, 1193-24-4, 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.

To cooled (0 C.) phosphorus oxychloride (20.0 mL, 215 mmol, 4.8 equiv.) was added DMF (6.4 mL, 83 mmol, 1.9 equiv) dropwise over 3 min. The reaction mixture was stirred for fifteen min and the ice bath was removed. 4,6-Dihydroxypyrimidine (5.0 g, 44.6 mmol, 1.0 equiv.) was added and the reaction mixture was heated to 130 C. and stirred for 3.5 hr. The mixture was cooled to RT and concentrated. Ice was slowly added to the dark brown residue, followed by 600 mL of ice water. The aqueous mixture was extracted with diethyl ether (5¡Á100 mL), and the organic extracts were washed with aqueous saturated NaHCO3 (2¡Á100 mL) and brine (100 mL), and dried over anhydrous sodium sulfate and concentrated in vacuo to provide Compound 15 (4.42 g, 57%) as a crude orange solid, which was used without further purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1193-24-4, its application will become more common.

Reference:
Patent; Sunesis Pharmaceuticals, Inc.; US2009/36419; (2009); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 3524-87-6, Adding some certain compound to certain chemical reactions, such as: 3524-87-6, name is 6-Methylpyrimidin-4(3H)-one,molecular formula is C5H6N2O, 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 3524-87-6.

To 70 g (0.64 mol) A-1 in acetic acid is added 127 g (0.56 mol) NIS portion wise at RT within 15 min. The reaction is stirred at RT until all starting material is consumed (30 h). The reaction mixture is diluted with water and the solid product is filtered off, washed with an aqueous sodium thiosulfate solution to remove excess iodine and dried in vacuo. Yield: 90 g (60%).

According to the analysis of related databases, 3524-87-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; WUNBERG, Tobias; KRAEMER, Oliver; van der VEEN, Lars; US2013/23533; (2013); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 16234-14-3, 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 16234-14-3 as follows.

2-Chlorothieno[3,2- Pd/C (8.90 mg, 20%> by wt) was added after 12 h. The reaction mixture was filtered through Celite with EtOAc washings. The filtrate was washed with H20/brine (4:1), dried (MgS04), and concentrated under reduced pressure to provide 16 (33.0 mg, 90%) as white solid: Mp 164.9-165.5 C (EtOAc); IR (ATR, neat) 3105, 3051, 2924, 1543, 1515, 1456, 1420, 1334, 1349, 1301, 1159, 794 cm”1; 1H NMR (DMSC fe 300 MHz) delta 9.50 (s, 1 H), 8.64 (d, 1 H, J= 5.4 Hz), 7.64 (d, 1 H, J= 5.4 Hz); 13C NMR (DMSO-d6, 75 MHz) delta 162.7, 156.3, 155.3, 142.2, 130.1, 122.9; MS (EI) m/z 170 (M+, 100), 135 (72);HRMS (EI) m/z calcd for C6H3N2SC1 169.9705, found 169.9700.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,16234-14-3, its application will become more common.

Reference:
Patent; UNIVERSITY OF PITTSBURGH – OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION; WIPF, Peter; WANG, Qiming, Jan; WO2012/78859; (2012); A2;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 130049-82-0, 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.130049-82-0, name is 3-(2-Chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidine-4-one, molecular formula is C11H15ClN2O2, molecular weight is 242.7, as common compound, the synthetic route is as follows.

A solution of oxalylchloride (8.8 ml) in dichloromethane (20 ml) was cooled to -65C and a solution of dimethyl sulfoxide (6.5 ml) dissolved in dichloromethane (20 ml) was added to it slowly and stirred for 30 min. keeping the temperature at -650C a solution of 3-(2-chloroethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[l,2-a]pyrimidin-4-one (5 grams) (formula-7) dissolved in dichloromethane (30 ml) was added to it very slowly and stirred for 40 min. Triethyl amine was added to the reaction mixture and then quenched with water. The organic layer was separated, washed with aqueous sodium carbonate and water. The solvent from the organic layer was distilled off under reduced pressure to provide the title compound. Yield: 4.0 grams

The chemical industry reduces the impact on the environment during synthesis 130049-82-0, I believe this compound will play a more active role in future production and life.

Reference:
Patent; MSN LABORATORIES LIMITED; SATYANARAYANA REDDY, Manne; ESWARAIAH, Sajja; SATYANARAYANA, Revu; WO2010/4578; (2010); A2;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 14161-09-2, name is 2-(Methylsulfonyl)pyrimidine, the common compound, a new synthetic route is introduced below. Quality Control of 2-(Methylsulfonyl)pyrimidine

Example 123 N-(2-((5-(4-(trifluoromethoxy)phenyl)benzo[d]isoxazol-3-yl)oxy)ethyl)pyrimidin-2-amine 2-((5-(4-(trifluoromethoxy)phenyl)benzo[d]isoxazol-3-yl)oxy)ethanamine hydrochloride (57 mg, 0.152 mmol) and 2-(methylsulfonyl)pyrimidine (96 mg, 0.608 mmol) were dissolved in 2 mL ethanol in a microwave vial. Triethylamine (0.1 mL) was added and the mixture was heated at 120 C. for one hour in the microwave. All volatiles were removed under vacuum and the residue was purified on 12 g silica gel with 0-100% ethyl acetate in hexane to give the title compound (40 mg, 0.096 mmol). MS: 417 (MH+).

The synthetic route of 14161-09-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Graupe, Michael; Lu, Yafan; Zablocki, Jeff A.; US2015/175560; (2015); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of 4316-97-6 ,Some common heterocyclic compound, 4316-97-6, molecular formula is C5H4Cl2N2, 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.

[00434] Step 2: Synthesis of 4,6-dichloro-2-(5-methoxy-2-(trifluoromethyl)phenyl)-5- methylpyrimidine. To a solution of 2-bromo-4-methoxy-1-(trifluoromethyl)benzene (5.0 g, 19.6 mmol) in dry THF (50 mL) stirred at -78 C under nitrogen atmosphere, was added n- Butyl lithium (8.9 mL, 2.4 M in hexane, 21.4 mmol) over a period of 5 minutes, the mixture was stirred for another 10 minutes at the same temperature before 4,6-dichloro-5- methylpyrimidine (4.5 g, 27.9 mmol) in THF (5 mL) was added slowly over 5 minutes. The resulting mixture was stirred at -78 C for 30 minutes, then quenched with HOAc (1.5 mL) and warmed to 0 C slowly. DDQ (6.6 g, 29.1 mmol) was then added portion wise and the resulting mixture was stirred at 0 C for 30 minutes, diluted with CH2Cl2(100 mL), washed with 10% NaOH (50 mL x 2) and brine (100 mL); the organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified silica column chromatography with (petroleum ether/EtOAc = 100/1 to 30/1) to render 4,6-dichloro-2-(5-methoxy-2- (trifluoromethyl) phenyl)-5-methylpyrimidine (1.0 g, 21% yield). ESI-LCMS (m/z): 337.0 [M+H]+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,4316-97-6, its application will become more common.

Reference:
Patent; EPIZYME, INC.; CHESWORTH, Richard; MORADEI, Oscar, Miguel; SHAPIRO, Gideon; JIN, Lei; BABINE, Robert, E.; (495 pag.)WO2016/44641; (2016); A2;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of 6299-85-0, 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. 6299-85-0, name is Methyl 2,6-dichloropyrimidine-4-carboxylate. A new synthetic method of this compound is introduced below.

EXAMPLE 8 Preparation of (S)-6-((l -amino- 1 -oxopropan-2-yl)amino)-2-(4-(4- (trifluoromethyl)phenoxy)phenyl)pyrimidine-4-carboxamide (Cpd No. 14) Scheme 17 (S)-methyl 2-chloro-6-((l -methoxy- 1 -oxopropan-2-yl)amino)pyrimidine-4- carboxylate: To a mixture of methyl 2,6-dichloropyrimidine-4-carboxylate (5.175 g, 25.00 mmol) in acetonitrile (100 mL) was added (S)-methyl 2-aminopropanoate hydrochloride (3.497 g, 25.05 mmol) and iPr2NEt (9.6 mL, 55.1 mmol). The mixture was heated at 50C overnight then concentrated in vacuo. The residue was chromatographed over silica gel with 30-70% EtOAc in hexanes. The product fractions were evaporated in vacuo to yield (S)-methyl 2-chloro-6-((l-methoxy-l – oxopropan-2-yl)amino)pyrimidine-4-carboxylate as a thick yellow-orange oil (4.194 g, 15.33 mmol, 61% yield). LC/MS: m/z= 274.2 [M+H]+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,6299-85-0, Methyl 2,6-dichloropyrimidine-4-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; PURDUE PHARMA L.P.; NI, Chiyou; PARK, Minnie; SHAO, Bin; TAFESSE, Laykea; YAO, Jiangchao; YOUNGMAN, Mark; WO2013/30665; (2013); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 3438-55-9, 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. 3438-55-9, name is 5-Bromo-4-chloro-6-methylpyrimidine. A new synthetic method of this compound is introduced below.

PREPARATIVE EXAMPLE 6 dl-5-bromo-6-methyl-4-(alpha-methylbenzylamino)pyrimidine (compound number 314) 2.0 g (0.02 mol) of triethylamine and 2.4 g (0.02 mol) of dl-alpha-methylbenzylamine were added to a solution of 4.15 g (0.02 mol) of 5-bromo-4-chloro-6-methyl-pyrimidine in 50 ml of benzene, and the mixture was refluxed with stirring for 5 hours. Upon completion of the reaction, the reaction product was washed with water, dried over anhydrous sodium sulphate and the benzene was distilled off to leave an oil. This oil was then caused to crystallize using column chromatography (Wakogel C-200, eluted with a 1:1 mixture of benzene and ethyl acetate). Crystals were obtained and recrystallized from n-hexane to give 2.6 g of the desired product in the form of pale yellow prisms melting at 85-87 C.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,3438-55-9, its application will become more common.

Reference:
Patent; Sankyo Company, Limited; Ube Industries, Limited; US4435402; (1984); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia