Category: 4994-86-9

Electric Literature of 4994-86-9, 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. 4994-86-9, name is 4-Chloro-2-methylpyrimidine, molecular formula is C5H5ClN2, 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.

General procedure: Two solutions, one with the aryl halide (0.56 mmol, 1.0equivalent) in THF-H2O (2.5 mL, 3:2 v/v) and one with phenol (0.84mmol, 1.5 equivalent) and NaOH (0.84 mmol, 1.5 equivalent) in THF-H2O(2.5 mL, 3:2 v/v) were prepared and then introduced into Asia microfluidicreactor by Pump A & B.. The mixture was pumped through a preheated 1 mL glassmicrofluidic reactor at a predetermined flow rate to achieve the desiredresidence time. The crude product was collected in a flask and extracted withethyl acetate. The organic phase was combined, dried MgSO4 andconcentrated under reduced pressure. The isolated crude product was purifiedusing a prepacked silica cartridge on a Teledyne CombiFlash Rf 200instrument. Fractions corresponding to the product peak were combined andconcentrated using rotavap. For the synthesis of compound 3e and 3f correspondingsodium alkoxides were used as input for the second pump.

According to the analysis of related databases, 4994-86-9, the application of this compound in the production field has become more and more popular.

Reference:
Article; Alam, Mohammad Parvez; Jagodzinska, Barbara; Campagna, Jesus; Spilman, Patricia; John, Varghese; Tetrahedron Letters; vol. 57; 19; (2016); p. 2059 – 2062;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Adding a certain compound to certain chemical reactions, such as: 4994-86-9, 4-Chloro-2-methylpyrimidine, 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, Quality Control of 4-Chloro-2-methylpyrimidine, blongs to pyrimidines compound. Quality Control of 4-Chloro-2-methylpyrimidine

A solution of 4-chloro-2-methylpyrimidine (100 mg, 0.778 mmol), 2-bromo- 5-fluoroisonicotinonitrile (156 mg, 0.778 mmol) and 1,1,1,2,2,2- hexamethyldistannane (255 mg, 0.778 mmol) in 1,4-dioxane (2 mL) was purged with nitrogen gas for 10 min. Pd(Ph3P)4 (90 mg, 0.078 mmol) was added to the reaction mixture and the solution was purged with nitrogen gas again for 10 min. The reaction mixture was heated in a microwave at 150 C for 2 h. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate (20 mL) and water (20 mL). The biphasic mixture was filtered through diatomaceous earth (Celite). The bed was washed with ethyl acetate (25 mL). The organic layer was separated, dried over Na2S04, filtered, and concentrated under reduced pressure. The brown solid was purified by silica gel chromatography (0- 40% EtOAc in pet ether) to afford 5-fluoro-2-(2-methylpyrimidin-4-yl) isonicotinonitrile (40 mg, 0.187 mmol, 24% yield) as an off-white color solid. LCMS (ESI) m/e 215.2 [(M+H)+, calcd for CnH8FN4 215.2]; LC/MS retention time (Method Al): = 1.76 min.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,4994-86-9, 4-Chloro-2-methylpyrimidine, and friends who are interested can also refer to it.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; BRONSON, Joanne J.; CHEN, Ling; DITTA, Jonathan L.; DZIERBA, Carolyn Diane; JALAGAM, Prasada Rao; LUO, Guanglin; MACOR, John E.; MAISHAL, Tarun Kumar; NARA, Susheel Jethanand; RAJAMANI, Ramkumar; SISTLA, Ramesh Kumar; THANGAVEL, Soodamani; (485 pag.)WO2017/59085; (2017); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Electric Literature of 4994-86-9, 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 4994-86-9 as follows.

General procedure: 3-(3-(4-(aminomethyl)benzyl)isoxazol-5-yl)pyridin-2-amine diformate (Intermediate D, 80mg, 0.22mmol) was dissolved in DMSO (0.5mL). N-ethyl-N-isopropylpropan-2 -amine (83mg, 0.65mmol) and 2,6-difluoropyridine (l48mg, l .29mmol) were added and the mixture was stirred for 2h at l20C. The mixture was diluted with water (l5mL) and extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with brine (10 mL), dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Si02, hexane/ethyl acetate) to yield N-(4-((5-(2-aminopyridin-3-yl)isoxazol-3-yl)methyl)benzyl)-6-fluoropyridin-2 -amine (47mg, 0T3mmol, 58%) as a white solid. 500 MHz NMR (DMSO-d6) d 8.08 (dd, .7= 4.8, 1.8 Hz, 1H), 7.86 (dd, J= 7.7, 1.8 Hz, 1H), 7.52 – 7.40 (m, 2H), 7.28 (s, 4H), 6.79 (s, 1H), 6.69 (dd, J= 7.7, 4.8 Hz, 1H), 6.35 (dd, J= 8.0, 2.5 Hz, 1H), 6.25 (s, 2H), 6.08 (dd, J= 7.6, 2.2 Hz, 1H), 4.38 (d, J= 6.0 Hz, 2H), 4.00 (s, 2H). MS: 376.3 [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,4994-86-9, its application will become more common.

Reference:
Patent; AMPLYX PHARMACEUTICALS, INC.; TRZOSS, Michael; COVEL, Jonathan; SHAW, Karen Joy; WEBB, Peter; (240 pag.)WO2019/113542; (2019); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of 4994-86-9, 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. 4994-86-9, name is 4-Chloro-2-methylpyrimidine, molecular formula is C5H5ClN2, 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.

A solution of 4-chloro-2-methylpyrimidine (0.050 g, 0.389 mmol), 5-(5- bromo-2-fluoropyridin-3-yl)oxazole (0.100 g, 0.389 mmol) and hexamethylditin (0.097 mL, 0.467 mmol) in 1,4-dioxane (0.1 mL) was purged with argon for 15 min and tetrakis(triphenylphosphine)palladium (0) (0.045 g, 0.039 mmol) was added. The reaction mixture was again purged with argon for 5 min and heated in a microwave for 1 h at 110C. The reaction mixture was diluted with ethyl acetate (8 mL) and water (5 mL) and the organic layer separated. The aqueous layer was extracted again with ethyl acetate (2×5 mL). The combined ethyl acetate layers were washed with brine, dried over Na2S04, filtered, and concentrated under reduced pressure. The reaction mixture was purified by Preparative TLC (70% ethyl acetate in hexanes). The required spot was collected, dissolved 5% methanol in dichloromethane (30 mL), filtered and concentrated under reduced pressure to afford 5-(2-fluoro-5-(2-methylpyrimidin-4-yl)pyridin-3-yl)oxazole (0.070 g, 0.098 mmol, 25% yield) as an off-white solid. LCMS (ESI) m/e 257.0 [(M+H) +, calcd for C13H10FN4O, 257.1]; LC/MS retention time (method B): /R = 0.86 min.

According to the analysis of related databases, 4994-86-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; BRONSON, Joanne J.; CHEN, Ling; DITTA, Jonathan L.; DZIERBA, Carolyn Diane; JALAGAM, Prasada Rao; LUO, Guanglin; MACOR, John E.; MAISHAL, Tarun Kumar; NARA, Susheel Jethanand; RAJAMANI, Ramkumar; SISTLA, Ramesh Kumar; THANGAVEL, Soodamani; (485 pag.)WO2017/59085; (2017); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 4994-86-9, 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 4994-86-9 as follows.

To a solution of N-((rac)-8-endo-3-benzyl-3-azabicyclo[3.2.1]octan-8-yl)-8-(3,4-difluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine (70 mg, 157 mumol) in methanol (1.6 mL) was added one drop of 25% aqueous hydrogen chloride solution under an atmosphere of nitrogen and stirring. The reaction was hydrogenated over night at 1 bar. The catalyst was filtered off and washed with ethanol. The solvent was evaporated under reduced pressure. The residue was dissolved in ethanol (1.6 mL). Triethylamine (47.7 mg, 65.7 muL, 471 mumol) and 4-chloro-2-methylpyrimidine (25.0 mg, 189 mumol) were added and the reaction was heated to 150 C. for 30 minutes in a microwave oven. The solvent was removed under reduced pressure after cooling to room temperature and the residue was purified by column chromatography on silica gel using a gradient from ethyl acetate to ethyl acetate/methanol (v/v 9:1) as eluent. The title compound was obtained as a light yellow solid (36 mg, 51%).MS ISP (m/e): 448.5 (100) [(M+H)+], 225.0 (80).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,4994-86-9, its application will become more common.

Reference:
Patent; Baumann, Karlheinz; Green, Luke; Limberg, Anja; Luebbers, Thomas; Thomas, Andrew; US2012/225884; (2012); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 4994-86-9 , The common heterocyclic compound, 4994-86-9, name is 4-Chloro-2-methylpyrimidine, molecular formula is C5H5ClN2, 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.

Pd(Ph3P)4 (37.7 mg, 0.033 mmol) was added to a mixture of 4-chloro-2-methylpyrimidine (117 mg, 0.913 mmol), 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-6-methyl-2-pyridinecarbonitrile D67 (150 mg), copper(I) iodide (22.35 mg, 0.117 mmol) and cesium fluoride (198 mg, 1.304 mmol) in 1,4-dioxane (3 ml) at room temperature. The mixture was degassed via 3 vacuum/nitrogen cycles and sonicated briefly to homogenise the reaction mixture which was then heated to 65 C. with shaking for 1 hour. The mixture was cooled and filtered washing with EtOAc. The organic phase was evaporated under reduced pressure. The residue was taken up in EtOAc (30 ml) and washed with NaHCO3 solution, dried (Na2SO4) and evaporated under reduced pressure. This residue was purified twice by flash chromatography on silica gel (Biotage Snap 25 g column, EtOAc/Cy from 50/50 to 100/0 then Biotage Snap 25 g column, isocratic Et2O) to give 85 mg of almost pure title compound. This material was purified further by recrystallisation from EtOH/Cy to give the title compound D80 (59 mg) as a yellow solid.UPLC (Acid QC_POS-50-800): rt=0.53 minutes, peak observed: 211 (M+1). C12H10N4 requires 210. 1H NMR (400 MHz, CDCl3) delta ppm 2.72 (s, 3H) 2.87 (s, 3H) 7.55 (d, 1H) 7.75 (d, 1H) 8.24 (d, 1H) 8.85 (d, 1H).

The synthetic route of 4994-86-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ALVARO, Giuseppe; Amantini, David; Castiglioni, Emiliano; Di Fabio, Romano; Pavone, Francesca; US2010/144760; (2010); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 4994-86-9, 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. 4994-86-9, name is 4-Chloro-2-methylpyrimidine, molecular formula is C5H5ClN2, 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.

A mixture of 4-chloro-2-methylpyrimidine (0.2 g, 1.556 mmol), (3-fluoro-4- methoxyphenyl)boronic acid (0.264 g, 1.556 mmol), and CS2CO3 (1.014 g, 3.11 mmol) in 1,4-dioxane (5 mL) and water (3 mL) was purged with nitrogen gas for 30 min. The reaction mixture was added PdCh (dppfJ-CfhCh adduct (0.127 g, 0.156 mmol) and was again purged with nitrogen gas for 10 min. The reaction mixture was heated at 80 C for 12 h. The reaction mixture was allowed to cool to room temperature and was concentrated under reduced pressure. The residue was taken up in ethyl acetate (50 mL) and water (40 mL), then the biphasic mixture was filtered through celite. The celite was washed with ethyl acetate (50 mL). The aqueous layer was separated out and the organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to afford a brown solid. The crude solid was purified by silica gel chromatography (EtOAc in pet ether) to afford 4-(3- fluoro-4-methoxyphenyl)-2-methylpyrimidine (0.128 g, 0.587 mmol, 38% yield) as a light yellow solid as an off-white color solid. LCMS (ESI) m/e 219.1 [(M+H)+, calcd for C12H12FN2O 219.1]; LC/MS retention time (method B): fe. = 0.69 min.

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 4994-86-9, 4-Chloro-2-methylpyrimidine.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; BRONSON, Joanne J.; CHEN, Ling; DITTA, Jonathan L.; DZIERBA, Carolyn Diane; JALAGAM, Prasada Rao; LUO, Guanglin; MACOR, John E.; MAISHAL, Tarun Kumar; NARA, Susheel Jethanand; RAJAMANI, Ramkumar; SISTLA, Ramesh Kumar; THANGAVEL, Soodamani; (485 pag.)WO2017/59085; (2017); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 4994-86-9 , The common heterocyclic compound, 4994-86-9, name is 4-Chloro-2-methylpyrimidine, molecular formula is C5H5ClN2, 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.

Pd(Ph3P)4 (37.7 mg, 0.033 mmol) was added to a mixture of 4-chloro-2-methylpyrimidine (117 mg, 0.913 mmol), 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-6-methyl-2-pyridinecarbonitrile D67 (150 mg), copper(I) iodide (22.35 mg, 0.117 mmol) and cesium fluoride (198 mg, 1.304 mmol) in 1,4-dioxane (3 ml) at room temperature. The mixture was degassed via 3 vacuum/nitrogen cycles and sonicated briefly to homogenise the reaction mixture which was then heated to 65 C. with shaking for 1 hour. The mixture was cooled and filtered washing with EtOAc. The organic phase was evaporated under reduced pressure. The residue was taken up in EtOAc (30 ml) and washed with NaHCO3 solution, dried (Na2SO4) and evaporated under reduced pressure. This residue was purified twice by flash chromatography on silica gel (Biotage Snap 25 g column, EtOAc/Cy from 50/50 to 100/0 then Biotage Snap 25 g column, isocratic Et2O) to give 85 mg of almost pure title compound. This material was purified further by recrystallisation from EtOH/Cy to give the title compound D80 (59 mg) as a yellow solid.UPLC (Acid QC_POS-50-800): rt=0.53 minutes, peak observed: 211 (M+1). C12H10N4 requires 210. 1H NMR (400 MHz, CDCl3) delta ppm 2.72 (s, 3H) 2.87 (s, 3H) 7.55 (d, 1H) 7.75 (d, 1H) 8.24 (d, 1H) 8.85 (d, 1H).

The synthetic route of 4994-86-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ALVARO, Giuseppe; Amantini, David; Castiglioni, Emiliano; Di Fabio, Romano; Pavone, Francesca; US2010/144760; (2010); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 4994-86-9, 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. 4994-86-9, name is 4-Chloro-2-methylpyrimidine, molecular formula is C5H5ClN2, 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.

A mixture of 4-chloro-2-methylpyrimidine (0.2 g, 1.556 mmol), (3-fluoro-4- methoxyphenyl)boronic acid (0.264 g, 1.556 mmol), and CS2CO3 (1.014 g, 3.11 mmol) in 1,4-dioxane (5 mL) and water (3 mL) was purged with nitrogen gas for 30 min. The reaction mixture was added PdCh (dppfJ-CfhCh adduct (0.127 g, 0.156 mmol) and was again purged with nitrogen gas for 10 min. The reaction mixture was heated at 80 C for 12 h. The reaction mixture was allowed to cool to room temperature and was concentrated under reduced pressure. The residue was taken up in ethyl acetate (50 mL) and water (40 mL), then the biphasic mixture was filtered through celite. The celite was washed with ethyl acetate (50 mL). The aqueous layer was separated out and the organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to afford a brown solid. The crude solid was purified by silica gel chromatography (EtOAc in pet ether) to afford 4-(3- fluoro-4-methoxyphenyl)-2-methylpyrimidine (0.128 g, 0.587 mmol, 38% yield) as a light yellow solid as an off-white color solid. LCMS (ESI) m/e 219.1 [(M+H)+, calcd for C12H12FN2O 219.1]; LC/MS retention time (method B): fe. = 0.69 min.

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 4994-86-9, 4-Chloro-2-methylpyrimidine.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; BRONSON, Joanne J.; CHEN, Ling; DITTA, Jonathan L.; DZIERBA, Carolyn Diane; JALAGAM, Prasada Rao; LUO, Guanglin; MACOR, John E.; MAISHAL, Tarun Kumar; NARA, Susheel Jethanand; RAJAMANI, Ramkumar; SISTLA, Ramesh Kumar; THANGAVEL, Soodamani; (485 pag.)WO2017/59085; (2017); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Electric Literature of 4994-86-9, 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. 4994-86-9, name is 4-Chloro-2-methylpyrimidine, molecular formula is C5H5ClN2, 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.

Under Ar(g), to a mixture of pyrazin-2-amine (1) (209mg, 2.2mmol), 4- chloro-2-methylpyrimidine (2) (257mg, 2.0mmol), Cs2C03 (1.30g, 4.0mmol) was added degassed dry 1 ,4-dioxane (13mL). The reaction mixture was then flushed with Ar(g) for 1 min before Pd2(dba)3 (92mg, 0.1 mmol) and Xantphos (127mg, 0.22mmol) were added. The reaction mixture was heated up to 90C for 40h. It was then cooled down to rt and concentrated in vacuo, CH2CI2 (15ml_) and H20 (15mL) were added. The organic phase was separated and the water layer was extracted with CH2CI2 (15ml_). The organic layers were combined and Pd- scavenger (MP-TMT, ~400mg, 1.3mmol/g) was added. This was shaken for several hours followed by filtration. The filtrate was concentrated in vacuo, dissolved in DMSO (4ml_) and purified by basic prep LCMS to yield (3) as a solid (184mg, 49%). (0590) LCMS (ES): Found 188.1 [M+Hf.

According to the analysis of related databases, 4994-86-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; KARUS THERAPEUTICS LIMITED; SHUTTLEWORTH, Stephen Joseph; GATLAND, Alice Elizabeth; FINNEMORE, Daniel John; ALEXANDER, Rikki Peter; SILVA, Franck; CECIL, Alexander; (233 pag.)WO2019/166824; (2019); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia