Pyrimidines

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.287714-35-6, name is Methyl 2-chloropyrimidine-5-carboxylate, molecular formula is C6H5ClN2O2, molecular weight is 172.57, as common compound, the synthetic route is as follows.Recommanded Product: 287714-35-6

To a solution of 6-(tert-butylsulfonyl)-N-(5-fluoro-lH-indazol-3-yl)-7-(2-(piperazin-l- yl)ethoxy)quinolin-4-amine (120 mg, 0.23 mmol) in NMP (2 mL) was added methyl 2- chloropyrimidine-5-carboxylate (47 mg, 0.27 mmol), and sodium bicarbonate (57 mg, 0.68 mmol) and the reaction was stirred at 110 C for lh. The residue was subjected directly to purification by flash chromatography (30g pre-packed C-18 SNAP cartridge: 30% to 85% acetonitrile (0.1% ammonia) in water (10 mM ammonium bicarbonate)). The desired fractions were combined and concentrated to afford the title compound (106 mg, 0.16 mmol, 70 % yield). LCMS T= 1.15 min, ES+ve 663.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,287714-35-6, Methyl 2-chloropyrimidine-5-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; CASILLAS, Linda N.; HARLING, John David; MIAH, Afjal Hussain; SMITH, Ian Edward David; RACKHAM, Mark David; (204 pag.)WO2017/182418; (2017); A1;,
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Related Products of 131860-97-4, 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 131860-97-4, name is (E)-Methyl 2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)-3-methoxyacrylate. This compound has unique chemical properties. The synthetic route is as follows.

Dimethylacetamide (DMAA, 400ml), 2-Cyanophenol (0.2M, 28g) and NaOH (0.225M, 9g) were placed at ambient temperature into the three-necked IL flask equipped with stirrer, condenser and thermometer. Half the amount of DMAA containing water traces was distilled at vacuum 20mbar/60-65C and the mixture was kept at vacuum 20mbar/ room temperature for Ih. The same amount of prime DMAA was added and Compound (I) (0.2M, 64g) was fed into the flask.The reaction mixture was heated to 100 C and kept at these conditions for 5 hours (monitored by HPLC – conversion of Compound (I) to Azoxystrobin 98-99%).DMAA was distilled at vacuum 20mbar/65-70C. At the end of the distillation the temperature can be increased up to 90-100C.40Og Butylacetate (BuAc) and 20Og water were added to the reaction mixture at 50-60C, the temperature was increased to 80C and stirred 10-15min. The water phase was separated at 800C to remove DMAA traces and inorganic salts.For crystallization the BuAc phase was slowly cooled from 800C to -5C. Filtration was done using filter No.2. The cake was washed with 60 ml cooled Butylacetate or methanol and further dried in oven at 80C during 15 hours. Azoxystrobin with purity 98-99% and a yield of 90-92% was obtained.

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 131860-97-4, (E)-Methyl 2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)-3-methoxyacrylate.

Reference:
Patent; MAKHTESHIM CHEMICAL WORKS LTD.; WO2008/75341; (2008); A1;,
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Adding a certain compound to certain chemical reactions, such as: 74901-69-2, 2,4-Dichloro-6,7-dihydrothieno[3,2-d]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, Quality Control of 2,4-Dichloro-6,7-dihydrothieno[3,2-d]pyrimidine, blongs to pyrimidines compound. Quality Control of 2,4-Dichloro-6,7-dihydrothieno[3,2-d]pyrimidine

Example 1 1.1 (2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)-(3-fluorophenyl)-amine (III-1) 4 g (II) are placed in 15 ml dimethylformamide, then 4.5 ml diisopropylethylamine and then 2.5 ml 3-fluorophenylamine are added. The reaction mixture is heated to 120 C., until no further reaction takes place, then cooled and evaporated down. The residue is mixed with water. The product is extracted with dichloromethane and purified by chromatography (silica gel, petroleum ether/ethyl acetate 80/20 to 60/40). 2.6 g (III-1) are obtained as a solid. Analytical HPLC (method A): RT=3.27 min.

The synthetic route of 74901-69-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; US2010/305102; (2010); A1;,
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Application of 32980-71-5, 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.32980-71-5, name is Perchloropyrimido[5,4-d]pyrimidine, molecular formula is C6Cl4N4, molecular weight is 269.9, as common compound, the synthetic route is as follows.

Connect a mineral oil valve rotating device, an impregnation thermometer, to a 4-cc bottle with a capacity of 100 cc.a vent and a drying tube, Add 7g piperidine and 30cc absolute ethanol to the bottle. Then, 2.7 g of tetrachloropyrimidopyrimidine was added with stirring. Increasing the reaction temperature to 32-35 C produces a moderate amount of basic steam. The powder reaction gradually changes from a yellow-gold-red crystal powder to a transparent granular powder.The tetrachloro compound is gradually added in 30 minutes. The reaction mixture was continuously stirred for 90 minutes and then allowed to stand for 24 hours. After the reaction was completed, it was observed that there was a bright yellow powder in the bright orange liquid, and the color of the liquid became more vivid when it was left standing. The precipitate was collected by filtration and washed with absolute ethanol to give 3.24 g of a yellow powder of unknown melting point which softened at 180 C and rapidly melted and decomposed at 240 C.The yellow powder was purified by adding 30 cc of dimethylformamide precooled at 0 C, and the dimethylformamide was turned into a deep red color. The precipitate was collected by suction filtration using a vacuum suction apparatus, and the residual dimethyl group was removed by washing with 10 cc of absolute ethanol. Formamide,The weight of the product is less than half the weight of the original material.The melting point is raised to 245 ~ 255 C, And softening occurs at 225 C. The average yield of the two chlorination reactions and subsequent reaction with piperidine is from 27 to 29%, based on the piperidine derivative, wherein the oxidized uric acid used in the chlorination reaction stage is in the form of its dried disodium salt.

Statistics shows that 32980-71-5 is playing an increasingly important role. we look forward to future research findings about Perchloropyrimido[5,4-d]pyrimidine.

Reference:
Patent; Suohao; Huan Xiaojun; Suo Hao; Qi Taotao; Jin Chunyan; Chen Yifei; (9 pag.)CN108752350; (2018); A;,
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Application of 5194-32-1, 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 5194-32-1 as follows.

General procedure: General CoulinQ Procedure 5 POd3 (3 eq.) was added to a stirred solution of carboxylic acid A (1 .0 eq.) and amine B (1 .0 eq.) in pyridine (25 mL) at 0 C. The reaction mixturewas stirred for I h at RT. The reaction mixture was then filtered and the filtrate was diluted with ethyl acetate (100 mL) then washed with water and brine (100 mL each). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to obtain the crude product, which was then purified by preparative H PLC.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,5194-32-1, its application will become more common.

Reference:
Patent; FROST BIOLOGIC, INC.; SIDDIQUI-JAIN, Adam; WO2015/127284; (2015); A2;,
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Synthetic Route 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.

To a solution of 2-(1-(6-fluoro-4-(2-methoxyethylamino)-3-phenylquinolin-2-yl)ethyl)isoindoline-1,3-dione (73.9 mg, 0.157 mmol) in EtOH (2 mL) was added hydrazine (0.049 mL, 1.574 mmol) and the resulting mixture was heated to 60 C. for 20 min. The reaction mixture was allowed to warm to rt and solid was filtered. The filtrate was concd under reduced pressure and used crude for the next step. To the crude solution of 2-(1-aminoethyl)-6-fluoro-N-(2-methoxyethyl)-3-phenylquinolin-4-amine (25 mg, 0.074 mmol) in BuOH (2 mL) was added DIEA (0.033 mL, 0.189 mmol) and 4-amino-6-chloropyrimidine-5-carbonitrile (24.33 mg, 0.157 mmol) and the resulting mixture was stirred at 110 C. overnight. The reaction mixture was cooled to rt and purified via HPLC.4-Amino-6-(1-(6-fluoro-4-((2-methoxyethyl)amino)-3-phenyl-2-quinolinyl)ethyl)amino)-5-pyrimidinecarbonitrile1H-NMR (400 Hz, CD3OD) delta ppm 1.53 (3H, d, J=7.24 Hz) 3.23 (2H, s) 3.33 (2H, m) 3.41 (2H, m) 4.99 (1H, m) 7.48 (1H, m) 7.64 (3H, m) 7.80 (2H, m) 8.03 (1H, s) 8.08 (1H, dd, J=9.39, 4.89 Hz) 8.22 (1H, dd, J=10.47, 2.64 Hz). Mass Spectrum (ESI) m/e=458 (M+1).4-Amino-6-(((1S)-1-(6-fluoro-4-((2-methoxyethyl)amino)-3-phenyl-2-quinolinyl)ethyl)amino)-5-pyrimidinecarbonitrile1H-NMR (400 Hz, CD3OD) delta ppm 1.30 (d, J=6.46 Hz, 3H) 3.18 (s, 3H) 3.19-3.22 (m, 2H) 3.28-3.31 (m, 2H) 5.25 (q, J=6.65 Hz, 1H) 7.37-7.41 (m, 1H) 7.43-7.47 (m, 1H) 7.48-7.55 (m, 2H) 7.55-7.61 (m, 2H) 7.82 (dd, J=10.76, 2.74 Hz, 1H) 7.94 (s, 1H) 8.01 (dd, J=9.29, 5.58 Hz, 1H). Mass Spectrum (ESI) m/e=458 (M+1).4-Amino-6-(((1R)-1-(6-fluoro-4-((2-methoxyethyl)amino)-3-phenyl-2-quinolinyl)ethyl)amino)-5-pyrimidinecarbonitrile1H-NMR (400 Hz, CD3OD) delta ppm 1.30 (d, J=6.65 Hz, 3H) 3.18 (s, 3H) 3.19 (d, J=1.56 Hz, 0H) 3.21 (d, J=5.28 Hz, 1H) 3.29-3.31 (m, 2H) 5.26 (q, J=6.52 Hz, 1H) 7.37-7.41 (m, 1H) 7.43-7.47 (m, 1H) 7.48-7.54 (m, 2H) 7.55-7.61 (m, 2H) 7.91-7.99 (m, 1H) 8.01 (dd, J=9.19, 5.67 Hz, 1H). Mass Spectrum (ESI) m/e=458 (M+1).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,60025-09-4, its application will become more common.

Reference:
Patent; AMGEN INC.; US2010/331306; (2010); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of 149849-94-5, 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. 149849-94-5, name is Methyl 2-chloropyrimidine-4-carboxylate, molecular formula is C6H5ClN2O2, 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 solution of methyl 2-chloropyrimindine-4-carboxylate (750 mg, 4.35 mmol) in methanol(20 mL) stirred under nitrogen at 0 C was added sodium borohydride (329 mg, 8.7 mmol)portion-wise. The reaction minxture was allowed to warm to rt and stirred at rt for 2 h. Asaturated solution of ammonium chloride in water (40 mL) and EtOAc (40 mL) were added.After separation, the aqueous layer was extracted with EtOAc (2 x 40 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and evaporated in vacuo to afford a brown oil. This residue was purified by normal phase column chromatography [(EtOHIEtOAc 4: 1)/CyH 0-40%j to afford (2-chloropyrimindin-4-yl)methanol (187 mg, 1.3 mmol, purity: 42 %, recovery: 30 %) as a light yellow solid. LCMS (m/z) 145 and 147 (M+H), retention time: 1.26 min LC/MS Method 1.

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 149849-94-5, Methyl 2-chloropyrimidine-4-carboxylate.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; DAUGAN, Alain Claude-Marie; DONCHE, Frederic G.; FAUCHER, Nicolas Eric; GEORGE, Nicolas S.; (243 pag.)WO2018/92089; (2018); A1;,
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Application of 31462-59-6, 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.31462-59-6, name is Pyrimidine-4-carboxylic acid, molecular formula is C5H4N2O2, molecular weight is 124.1, as common compound, the synthetic route is as follows.

General Procedure 13 was followed in the preparation of Intermediate 19. 2129 General Procedure 13 2131 Intermediate 19 2132 [0243] Thionyl chloride (3.55mL, 48.4 mmol, 3 eq) was added dropwise to a solution of 2133 pyrimidine-4-carboxylic acid (2 g, 16.1 mmol) in EtOH (15 mL) and the resulting mixture 2134 was heated to reflux for 14 h. The mixture was then cooled to RT and made alkaline with 2135 saturated aqueous NaHC03 to pH 8. The basic solution was then extracted with EtOAc (4 x 2136 50 mL). The combined organic layers were washed with brine (30 mL), dried over Na2S04, 2137 filtered and concentrated in vacuo to afford Intermediate 19 (1.7g, 77%). 1H NMR: (DMSO- 2138 d6) 5 9.40 (d, J= 1.0 Hz, 1H), 9.10 (d, J= 5.1 Hz, 1H), 8.05 (dd, J= 5.1, 1.3 Hz, 1H), 4.39 2139 (q, J= 7.1 Hz, 2H), 1.35 (t, J= 7.1 Hz, 3H); MS: 153 [M + H]+; TLC: 40% hexane in EtOAc: 2140 Rf: 0.40

The chemical industry reduces the impact on the environment during synthesis 31462-59-6, I believe this compound will play a more active role in future production and life.

Reference:
Patent; VERSEON, INC.; SHORT, Kevin, Michael; PHAM, Son, Minh; WILLIAMS, David, Charles; KITA, David, Ben; WO2014/145986; (2014); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 941685-26-3, 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. 941685-26-3, name is 4-Chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine. A new synthetic method of this compound is introduced below.

4- chloro-7 – ((2- (trimethylsilyl) ethoxy) methyl) -7H-pyrrolo [2,3-d] pyrimidine (Compound A, 500mg, 1.25mmol, 1.0eq) and5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolane hetero-pentyl 2-yl) -7-tosyl–7H- pyrrolo [2,3-d] pyrimidine(Compound B, 392mg, 1.38mmol, 1.1eq) was dissolved in DME (10mL) mixture / 2M sodium carbonate solution (5mL) was added Pd (PPh3) 4 (144mg, 0.125mmol, 0.1eq) under N2 atmosphere, after addition was complete the reaction was warmed to reflux for 3h. TLC monitored the reaction was complete (Rf = 0.1, PE: EA = 3: 1), cooled to room temperature and added to H2O (30mL) and EA (50 mL) separated, aqueous phase extracted with EA three times, the combined organic phase was washed with saturated brine once, after the organic phase was dried over anhydrous magnesium sulfate, and column chromatography (PE: EA = 3: 1-1: 1) give 224 mg of a pale yellow solid (compound C).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,941685-26-3, 4-Chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine, and friends who are interested can also refer to it.

Reference:
Patent; Jiangsu Kefeiping Pharmaceutical Co., Ltd.; Nanjing Kefeipingshenghui Pharmaceutical Co., Ltd.; Nanjing Kefeiping Pharmaceutical Co., Ltd.; Qin Yinlin; Su Mei; Jin Qiu; Chen Tao; Wu Xianzhi; Jiang Jianhua; (15 pag.)CN105524067; (2016); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 4595-59-9, 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 4595-59-9 as follows.

An oven dried 5 mL microwave vial with a 10 mm stir bar was charged with 5-bromopyrimidine (115 mg, 0.5 mmol), naphthalene-1-boronic acid (152 mg, 1.0 mmol) and tribasic potassium phosphate monohydrate (288 mg, 1.25 mmol). The vial was equipped with a septum and subjected to three evacuation/Argon backfill cycles. A toluene solution (0.1 mL) of Pd(OAc)2 (0.56 mg, 0.0025 mmol) and EvanPhos (1.8 mg, 0.0038 mmol) was added via syringe followed by toluene (0.9 mL). The reaction was stirred in an oil bath at 40 C. under argon. GC/MS monitoring showed complete consumption of the halide after 6 h. The vessel was cooled to rt and diluted with water (1 mL). The aqueous phase was extracted in flask with EtOAc (3*1 mL). The combined organic phases were flushed over a short plug of silica gel in a pasteur pipette and then washed with EtOAc. Volatiles were removed in vacuo. The mixture was chromatographed over silica gel eluting with 1:3 diethyl ether:hexanes (Rf=0.20, 3:7 diethyl ether:hexanes) which yielded an off-white powder (99 mg, 96%). 1H NMR (400 MHz, chloroform-d) delta 9.31 (s, 1H), 8.89 (s, 2H), 7.95 (dd, J=8.4, 3.7 Hz, 2H), 7.75 (d, J=8.2 Hz, 1H), 7.61-7.48 (m, 3H), 7.42 (d, J=7.0 Hz, 1H). 13C NMR (101 MHz, chloroform-d) delta 157.72, 157.40, 134.44, 133.87, 132.50, 131.26, 130.95, 129.53, 128.78, 127.84, 127.18, 126.54, 125.52, 124.65.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,4595-59-9, its application will become more common.

Reference:
Patent; The Regents of the University of California; Lipshutz, Bruce H.; Handa, Sachin; Landstrom, Evan; (35 pag.)US2018/117574; (2018); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia