Day: March 4, 2021

Synthetic Route of 633328-98-0, 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.633328-98-0, name is 5-Chloro-1H-pyrazolo[4,3-d]pyrimidine, molecular formula is C5H3ClN4, molecular weight is 154.5571, as common compound, the synthetic route is as follows.

Step 1A mixture of of 5 -chioro- 1 H-pyrazolo [4,3 -d]pyrimidine (1 g, 6.47 mmol) and NIS (1.747 g, 7.76 mmol) in acetonitrile (6 mL) in a microwave sealed tube was heated to 120C for 40 mm in an oil bath. Then the reaction was cooled down and concentrated to dryness. The residue was purified via gradient C18 chromatography [ISCO, 0 – 100 % water(0.1% TFA) in acetonitrile(0,1% TFA)] which furnished Intermediate Hi.

Statistics shows that 633328-98-0 is playing an increasingly important role. we look forward to future research findings about 5-Chloro-1H-pyrazolo[4,3-d]pyrimidine.

Reference:
Patent; MERCK SHARP & DOHME CORP.; DEMONG, Duane; GRESHOCK, Thomas, J.; CHANG, Ronald, K.; DAI, Xing; LIU, Hong; MCCAULEY, John, A.; LI, Wei; BASU, Kallol; SCOTT, Jack, D.; MILLER, Michael; WO2015/26683; (2015); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Adding a certain compound to certain chemical reactions, such as: 113583-35-0, 2-Methanesulfonyl-4,6-dimethoxypyrimidine, 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, name: 2-Methanesulfonyl-4,6-dimethoxypyrimidine, blongs to pyrimidines compound. name: 2-Methanesulfonyl-4,6-dimethoxypyrimidine

EXAMPLE 1 Preparation of 5-(4,6-dimethoxypyrimidin-2-yl)oxy-4-formyl-3-methylbenzothiophene (Compound No. 104) A mixture comprising 2.1 g of 4-formyl-5-hydroxy-3-methylbenzothiophene, 2.4 g of 4,6-dimethoxy-2-methylsulfonylpyrimidine and 1.8 g of potassium carbonate in 30 ml of N,N-dimethylformamide, was heated and stirred at 70 C. for 3 hours. The mixture was returned to room temperature, then poured into water and extracted with ethyl acetate. The organic layer was washed with water and then dried over anhydrous sodium sulfate. Then, it was concentrated under reduced pressure, and the oily substance thereby obtained was purified by silica gel column chromatography (n-hexane/ethyl acetate=10/1) to obtain 3.1 g (yield: 86%) of the desired compound.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,113583-35-0, 2-Methanesulfonyl-4,6-dimethoxypyrimidine, and friends who are interested can also refer to it.

Reference:
Patent; Kumiai Chemical Industry Co., Ltd.; Ihara Chemical Industry Co., Ltd.; US5616537; (1997); A;,
Pyrimidine | C4H4N2 – PubChem,
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. 1514-96-1, name is 4-Chloro-2-(trifluoromethyl)pyrimidine, molecular formula is C5H2ClF3N2, 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. Product Details of 1514-96-1

To a stirred solution of tert-butyl 4-[(2-{[6-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 Hbenzimidazol-2-yl]amino}pyridmn-4-yl)methyl]piperazine-1 -carboxylate (500 mg, 936 pmol) and4-chloro-2-(trifluoromethyl)pyrimidine (307 mg, 1.68 mmol) in dioxane (5 mL) and water (0.9 mL) was added sodium carbonate (297 mg, 2.81 mmol) and Pd(dppf)C12 . CHCl (115 mg, 140 pmol). The mixture was heated to reflux for 24 h. Dichioromethane was added, the mixture was dried (magnesium sulfate), filtered and the solvent was removed in vacuum. Silicagel chromatography gave 540 mg (83 % yield) of the title compound.LC-MS (Method 2): Rt = 1.40 mm; MS (ESIpos): m/z = 555 [Mi-H]

With the rapid development of chemical substances, we look forward to future research findings about 1514-96-1.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; SCHULZE, Volker; HEINRICH, Tobias; PRINZ, Florian; LEFRANC, Julien; SCHROeDER, Jens; MENGEL, Anne; BONE, Wilhelm; BALINT, Joszef; WENGNER, Antje; EIS, Knut; IRLBACHER, Horst; KOPPITZ, Marcus; BOeMER, Ulf; BADER, Benjamin; BRIEM, Hans; LIENAU, Philip; CHRIST, Clara; STOeCKIGT, Detlef; HILLIG, Roman; (1256 pag.)WO2017/102091; (2017); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Electric Literature of 22536-65-8, Adding some certain compound to certain chemical reactions, such as: 22536-65-8, name is 2-Chloro-5-methoxypyrimidine,molecular formula is C5H5ClN2O, 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 22536-65-8.

[0595] Synthesis of methyl 5-methoxypyrimidine-2-carboxylate: [0596] To a stirred solution of 2-chloro-5-methoxypyrimidine (1 g, 6.92 mmol) in MeOH: CH3CN (4: 1, 20 mL) under argon atmosphere were added Pd(dppf)Cl2 (1 g, 1.38 mmol) and triethyl amine (1.9 mL, 13.84 mmol) at RT; heated to 100 C and stirred for 16 h in steel bomb under CO pressure. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was filtered through celite and the filtrate was concentrated in vacuo to obtain the crude. The crude was purified through silica gel column chromatography using 60% EtOAc/ Hexanes to afford methyl 5-methoxypyrimidine-2-carboxylate (600 mg, 52%) as brown solid. [0597] 1H-NMR (CDC13, 400 MHz): delta 8.54 (s, 2H), 4.06 (s, 3H), 4.00 (s, 3H); LC-MS: 98.52%; 169 (M++l); (column: X Bridge C-18, 50 3.0 mm, 3.5 mupiiota); RT 2.26 min. 0.05% Aq TFA: ACN; 0.8 mL/min); TLC: 70% EtOAc/ Hexanes (R 0.2).

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. 22536-65-8, 2-Chloro-5-methoxypyrimidine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ENVIVO PHARMACEUTICALS, INC.; RIPKA, Amy; SHAPIRO, Gideon; MCRINER, Andrew, J.; BURSAVICH, Matthew, Gregory; WO2013/142269; (2013); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 274693-26-4, 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. 274693-26-4, name is 2-(((3aR,4S,6R,6aS)-6-(7-(((1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl)amino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol, molecular formula is C26H32F2N6O4S, 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.

3) Operation process(1) cooling the toluene solution of the upper step product remaining in the 200L reaction vessel to 10 to 20 C;(2) adding 37.062 kg of hydrochloric acid and 55 L of methanol mixed solution cooled to 10 to 20 C into the reaction kettle under stirring;After the addition is completed, the mixture is kept at 10 to 20 C for 3 to 4 hours;(3) TLC detection reaction was completed, ethyl acetate: isooctane=1:1, taking the upper organic phase point plate;Stop stirring, let stand for stratification, and separate the lower methanol water phase for use;(4) Add 500 ml of the lower methanol aqueous phase separated in the above step, and add 20% potassium carbonate aqueous solution with stirring.(25.406 kg of potassium carbonate and 101.64 L of purified water); finally adjusted pH between 7-9;(5) adding 55 L of ethyl acetate under stirring, and stirring for 30 min;Stop stirring, let stand layering, separate the lower layer of water, and transfer the upper organic phase to the PE barrel for use;(6) The lower aqueous phase was transferred to the reaction vessel, 55 L of ethyl acetate was added, and the mixture was stirred for 30 min; the stirring was stopped, and the layer was allowed to stand.Divide the lower aqueous phase;(7) Combine the two organic phases, add 200L reaction kettle, add 55L purified water with stirring, stir for 30 minutes; stopStirring, standing layering, separating the lower aqueous phase; adding 55 L of purified water to the reactor, stirring for 30 minutes; stopping stirring, quenchingLayering, separating the lower aqueous phase;(8) Add 686 g of activated carbon to the organic phase (the amount of activated carbon is 5% of the crude product, and the crude product is 100% yield)Calculated), heated to 40 ~ 50 C, stirred for 30 minutes;(9) Filter the filter pad with diatomaceous earth (about 100g of diatomaceous earth), distill off the solvent under reduced pressure at 50 C, steam until no more liquidThe body is effluent; add 11 L of ethyl acetate to distill off the solvent, repeat 2 times until the solid is produced, no more liquid will flow out;Add 68.61 L of ethyl acetate and heat to 50-60 C to dissolve (the amount of ethyl acetate is 5 times the mass of the crude product, the crude product is100% yield calculation); transfer the solution into a 50L reaction kettle, heated to 50 ~ 60 C;(10) Add 82.33L of isooctane preheated to 50-60 C under stirring (the amount of isooctane is ethyl acetate volume)1.2 times); control the addition speed to keep the internal temperature above 50 C, and gradually precipitate solids during the addition;(11) After the addition is completed, the temperature is lowered by stirring to a temperature of 20 to 30 C, and stirred for 1 hour;(12) further cooling to 0 to 10 C and stirring for 2 hours;(13) Centrifugal filtration, the reaction kettle and the filter cake were pretreated to 13.72 L of ethyl acetate and 16.47 L of isothermally cooled to 0 to 10 C.Washed with octane mixed solvent;(14) The filter cake is dried under vacuum at 45-55 C for 8 to 12 hours to obtain 11.6 kg of crude tigrilo (Im-4);85; 1) Add 45 L of dichloromethane and 108 L of tert-butanol to a 200 L crystallizer; stir and add 11.5 kg of ticagrelor.Product,(2) heating to 50 ~ 60 C under stirring for 1 hour; cooling to 20 ~ 30 C, stirring for 1 hour;(3) further cooling to 0 to 10 C for 2 hours;(5) centrifugal filtration, the reaction kettle and the filter cake are rinsed with water precooled to 0 to 10 C;(6) The filter cake was dried under vacuum at 45-55 C for 8 to 12 hours to obtain 10.7 kg of ticagrelor; the weight yield was 93%.

According to the analysis of related databases, 274693-26-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Hebei Kaiwei Pharmaceutical Co., Ltd.; Pang Yuning; (23 pag.)CN108276417; (2018); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of 2915-16-4, 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 2915-16-4 as follows.

Example 90; [4- (4, 6-Diphenylpyrimidin-2-yl) -phenyl]methanol; A mixture of 2-chloro-4, 6-diphenylpryimidine, 0.79g (2.96 mmol), 4- (hydroxylmethyl)phenylboronic acid, 0.45g (2.96 mmol), Pd (PPh3) 4, 342mg (0.296 mmol), in 2 mL of toluene and EPO ImL of methanol was heated to obtain a clear solution. To the solution was added 2mL of 4.0M aq. Na2CO3. The reaction mixture refluxed for lbetah at 70 C. The mixture was cooled to room temperature and diluted with 10OmL ethyl acetate. The organic layer was washed with water, sat. aq. NaCl, and dried (MgSO4) . After the solution was concentrated, the residue was recrystallized with Et2O-Heptane (1:1) to afford the desired product in 0.38g (38%) as a yellow solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,2915-16-4, its application will become more common.

Reference:
Patent; THE INSTITUTES FOR PHARMACEUTICAL DISCOVERY, LLC; WO2006/55725; (2006); A2;,
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 1005-37-4, name is 6-Chloro-N4-methylpyrimidine-2,4-diamine. This compound has unique chemical properties. The synthetic route is as follows. Quality Control of 6-Chloro-N4-methylpyrimidine-2,4-diamine

Example 508 {2-[2-amino-6-(methylamino)pyrimidin-4-yl]phenyl}methanol 6-chloro-4-N-methylpyrimidine-2,4-diamine (20 mg, 0,13 mmol), 1 ,3-dihydro-2, 1- benzoxaborol-1-ol (25 mg, 0, 19 mmol), K2C03 (78 mg, 0,57 mmol), Tetrakis(triphenylphosphine)palladium(0) (7,3 mg, 0,0060 mmol), MeCN (1 ,5 mL) and water (0,5 mL) were heated in the micro for 10 min at 120C. The organic phase was filtered and purified by basic prep-HPLC to afford {2-[2-amino-6- (methylamino)pyrimidin-4-yl]phenyl}methanol. LCMS [M+H]+ 231

With the rapid development of chemical substances, we look forward to future research findings about 1005-37-4.

Reference:
Patent; THOMAS HELLEDAYS STIFTELSE FOeR MEDICINSK FORSKNING; SCOBIE, Martin; WALLNER, Olov; KOOLMEISTER, Tobias; VALLIN, Karl Sven Axel; HENRIKSSON, Carl Martin; HOMAN, Evert; HELLEDAY, Thomas; JACQUES, Sylvain; DESROSES, Matthieu; JACQUES-CORDONNIER, Marie-Caroline; FISKESUND, Roland Julius Yu; (359 pag.)WO2015/187089; (2015); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Adding a certain compound to certain chemical reactions, such as: 705-24-8, 4,6-Dichloro-2-(trifluoromethyl)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, 705-24-8, blongs to pyrimidines compound. Recommanded Product: 4,6-Dichloro-2-(trifluoromethyl)pyrimidine

To 4,6-dichloro-2-(trifluoromethyl)pyrimidine (300 mg 1.38 mmol) in Dioxane (3 ml) was added ammonia solution (1 ml). The reaction was heated under microwave activation, at 100C for 20 min. After cooling, excess solvent was evaporated under reduced pressure. The obtained residue was taken to the next step without further purification. LC/MS: m/z 198 (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,705-24-8, its application will become more common.

Reference:
Patent; HELMHOLTZ-ZENTRUM FUeR INFEKTIONSFORSCHUNG GMBH; AHMED, Ahmed S. A.; EMPTING, Martin; HAMED, Mostafa; HARTMANN, Rolf W.; HAUPENTHAL, Joerg; HASTERKAMP, Thomas; KAMAL, Ahmed A. M.; MAURER, Christine K.; ROeHRIG, Teresa; SCHUeTZ, Christian; YAHIAOUI, Samir; ZENDER, Michael; (128 pag.)WO2020/7938; (2020); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Adding a certain compound to certain chemical reactions, such as: 10320-42-0, 2-Chloro-5-nitropyrimidine, 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, 10320-42-0, blongs to pyrimidines compound. name: 2-Chloro-5-nitropyrimidine

A mixture of 2-chloro-5-trifluoromethyl-benzeneboronic acid (c, 200 mg), 2-chloro-5-nitro-pyrimidine (f, 100 mg), Pd(PPh3)4 (0.05 mmol), sodium bicarbonate (2 mmol) in a mixture of toluene (20 mL), water (5 mL), ethanol (2 mL) was heated at 80¡ã C. for 24 h. The mixture was taken up with EtOAc (100 mL), washed with water (2.x.100 mL) and dried (Na2SO4). The oil obtained on concentration was passed through a layer of silica gel to get compound g as a crude mixture.The above mixture was treated with SnCl2 (200 mg) in ethanol (EtOH) (5 mL) for 16 h. The mixture was diluted with water (50 mL) and extracted with DCM (2.x.50 mL). The DCM layer was dried, evaporated and passed through silica gel to afford compound h as a crude mixture. The above mixture was treated with 2,6-difluorobenzoic acid (100 mg) and EDC (150 mg) in DCM (5 mL) for 16 h. The mixture was washed with water and purified by column chromatography to give N-[2-(2-chloro-5-trifluoromethyl-phenyl)-pyrimidin-5-yl]-2,6-difluoro-benzamide as white solid (Compound 122, 10 mg). 1H-NMR (CDCl3) delta 9.28 (s, 2H), 8.09 (s, 1H), 8.0 (br, 1H), 7.63 (s, 2H), 7.5 (m, 1H), 7.1 (t, 2H, J=8) ppm; ESMS calcd for C18H9ClF5N3O: 413.0; found: 414.0 (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,10320-42-0, its application will become more common.

Reference:
Patent; Synta Pharmaceuticals Corp.; US2006/173021; (2006); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application 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 55; N-hydroxy-2-(hydroxyamino)-6-(4-(pyridin-3-ylethynyl)phenyl)pyrimidine-4- carboxamide, trifluoroacetic acid salt; A. Methyl 2-chloro-6-(4-(pyridin-3-ylethynyl)phenyl)pyrimidine-4-carboxylate; Methyl 2,6-dichloropyrimidine-4-carboxylate (0.5 g, 2.4 mmol), 3-((4-(5,5-dimethyl- l,3,2-dioxaborinan-2-yl)phenyl)ethynyl)pyridine (0.35 g, 1.2 mmol, Method 2), K2CO3 (0.33 g, 2.4 mmol) and [l,4-bis(diphenylphospino)butane]palladium(II) dichloride (0.073 g, 0.12 mmol) were combined in dioxane (3 mL)/water (1 mL), purged with Argon and heated to 150 0C in the microwave. The reaction was stirred for 30 min. LC-MS after 30 minutes indicates reaction is complete as a mixture of ester and acid. The reaction mixture was diluted with water, neutralized with IN HCl, and extracted three times with ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered and evaporated. The solid was dissolved in MeOH and trimethylsilyldiazomethane (2.4 mL, 4.8 mmol) was added. LC-MS after 15 minutes indicated formation of the methyl ester was complete. The reaction mixture was diluted with water and extracted three times with ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered and evaporated to a solid (0.2Og, 23.7% yield). LC-MS: [M+H]+ 350 Mass: calculated for Ci9Hi2ClN3O2, 349.77

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; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; BENENATO, Kerry, Ellen; CHOY, Allison, Laura; HALE, Michael, Robin; HILL, Pamela; MARONE, Valerie; MILLER, Matthew; WO2010/100475; (2010); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia