Pyrimidines

1500-85-2, 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. 1500-85-2, name is 7H-Pyrrolo[2,3-d]pyrimidin-4-amine, molecular formula is C6H6N4, 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: Procedure G: To a solution of 7H-pyrrolo[2,3-d]pyrimidin-4-amine (1, 0.32 g, 2.39 mmol) and 2?-chloro-4?-methylspiro[cyclohexane-1,7?-pyrrolo[3,4-b]pyridin]-5?(6?H)-one (2, 0.6 g, 2.39 mmol) in 1,4-dioxane (15 mL) was added cesium carbonate (2.33 g, 7.17 mmol). The reaction mixture was purged with argon for 5 min. and then XanthPhos (69 mg, 0.11 mmol), XPhos (57 mg, 0.11 mmol), tris(dibenzylideneacetone)dipalladium(0) (109 mg, 0.11 mmol) and palladium acetate (27 mg, 0.11 mmol) were added and the reaction mixture purged for an additional 5 min. The purged reaction mixture was stirred at 100 C. for 4 h. After TLC showed completion, the reaction mixture was filtered through a bed of celite and the resulting filtrate was concentrated. The crude product was purified by preparative HPLC. The desired fractions were concentrated to dryness under vacuum to afford 2?-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-4?-methylspiro[cyclohexane-1,7?-pyrrolo[3,4-b]pyridin]-5?(6?H)-one as a yellow solid. Yield: 0.095 g, 11%;

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. 1500-85-2, 7H-Pyrrolo[2,3-d]pyrimidin-4-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; EFFECTOR THERAPEUTICS, INC.; Sprengeler, Paul A.; Reich, Siegfried H.; Ernst, Justin T.; Webber, Stephen E.; (55 pag.)US2017/121339; (2017); A1;,
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3934-20-1, 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. 3934-20-1, name is 2,4-Dichloropyrimidine. A new synthetic method of this compound is introduced below.

A mixture of 2,4-dichloroprymidine 5 (1.00g, 6.7mmol), phenylboronic acid (0.99g, 8.1mmol), (1,1?-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (0.51g, 0.7mmol) and sodium carbonate (2.13g, 20.1mmol) in DMF/1,4-dioxane/water (4:2:1, 10mL) was degassed with nitrogen and stirred at 80C for 10h. After completion of the reaction, the reaction mixture was diluted with dichloromethane (50ml), washed with brine (30mL¡Á3), dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by chromatography (ethyl acetate/petroleum ether) on silica gel to give 8h as a white solid (70%): mp 87.7-88.2C; 1H NMR (400MHz, CDCl3) delta: 8.65 (d, J=5.3Hz, 1H), 8.11 (dd, J=8.1, 1.9Hz, 2H), 7.66 (d, J=5.3Hz, 1H), 7.58-7.51 (m, 3H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,3934-20-1, 2,4-Dichloropyrimidine, and friends who are interested can also refer to it.

Reference:
Article; Sun, Wuji; Hu, Shengquan; Fang, Shubiao; Yan, Hong; Bioorganic Chemistry; vol. 78; (2018); p. 393 – 405;,
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4595-59-9 , The common heterocyclic compound, 4595-59-9, name is 5-Bromopyrimidine, molecular formula is C4H3BrN2, 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.

General procedure: Benzyl bromide (1 mmol), alkyl halide (1.1 mmol), thiourea (1.2 mmol), and K2CO3(3 mmol) were added to 5 mL of DMF at 100 C. The reaction was stopped after the consumptionof the benzyl bromide, which was monitored by gas chromatography (GC). Then, the reaction mixture was diluted with de-ionized water and extracted with CH2Cl2. Thecombined organic extracts were dried over anhydrous MgSO4, filtered, and concentrated byrotary evaporation to generate a crude product. Purification by silica gel chromatographyeluting with n-hexane afforded pure thioethers.

The synthetic route of 4595-59-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Lu, Xiaogang; Wang, Hongmei; Gao, Runli; Pei, Chengxin; Phosphorus, Sulfur and Silicon and the Related Elements; vol. 190; 1; (2015); p. 45 – 52;,
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49845-33-2 , The common heterocyclic compound, 49845-33-2, name is 2,4-Dichloro-5-nitropyrimidine, molecular formula is C4HCl2N3O2, 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.

A solution of methyl amine-ethanol(7.6ml) and N,N-diisopropylethylamine(13.2ml) were dissolved into 150ml dichloromethane. The mixture was added dropwise to a solution of 2,4-dichloro-5-nitropyrimidine(10.0g) in dichloromethane(30ml) at 0¡ãC. After the completion of the dropwise addition, the mixture was kept at the same temperature to react for half an hour. Purification was conducted by a column chromatography to obtain a yellow solid(8.3g) in a yield of 85.4percent.?1H NMR(400 MHz, CDCl3): delta 9.05(s, 1H), 8.41(s, 1H), 3.22(s, 3H)ppm.

According to the analysis of related databases, 49845-33-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Si Chuan University; CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.; YANG, Shengyong; WEI, Yuquan; EP2578584; (2013); A1;,
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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. 7752-82-1, name is 5-Bromopyrimidin-2-amine. A new synthetic method of this compound is introduced below., 7752-82-1

To a solution of 2-amino pyridine (30 g, 0.31 mol) in DME (120 mL) was added chloro acetone (40.5 mL, 0.47 mol) at room temperature. The reaction mixture was heated to reflux, and then stirred for 48 hours. The volatiles were concentrated under reduced pressure. Then the residue was purified by column chromatography eluting with 1% MeOH/DCM to afford Int-2 (20 g, 48%) as a liquid. Mass (m/z): 133 [M++1]. 1H NMR (200 MHz, dmso-d6): delta8.05 (d, J=8.2 Hz, 1H), 7.35 (s, 1H), 7.1 (t, J=6.8 Hz, 1H), 6.7 (t, J=6.8 Hz, 1H), 6.5 (d, J=8.2 Hz, 1H), 2.45 (s, 3H). To a solution of Int-2 (10 g, 76.7 mmol) in acetonitrile (50 mL) was added N-iodo succinamide (20.4 g, 80 mmol) portion wise at room temperature and then stirred for 48 hours. The precipitated solid was filtered off. The crude material was re-crystallized from ethyl acetate/water to afford Int-3 (9 g, 49%) as solid. Mass (m/z): 259 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 8.22 (d, J=8 Hz, 1H), 7.47 (d, J=7.2 Hz, 1H), 7.29 (t, J=7.0 Hz, 1H), 2.35 (s, 3H). To a solution of Int-3 (6.0 g, 29.2 mmol) in IPA-H2O (75 mL, 2:1) was added PdCl2(dppf).DCM (4.7 g, 5.8 mmol), followed by the addition of tert-butyl amine (3.1 g, 43.8 mmol) at room temperature and the resulting reaction mixture was degassed for 15 minutes. Then Int-4 (2.9 g, 18.6 mmol) was added to the reaction mixture at room temperature. The reaction mixture was heated to 100 C. and then stirred for 16 hours. The reaction mixture was diluted with water (100 mL), extracted with EtOAc (3¡Á100 mL), washed with water, brine and dried over anhydrous Na2SO4. The organic layer was concentrated under reduced pressure. The crude material was purified by column chromatography eluting with 1% MeOH/DCM to afford Int-5 (1.6 g, 28%). Mass (m/z): 244 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 8.51 (t, J=5 Hz, 2H), 7.71 (s, 1H), 7.63-7.55 (m, 2H), 7.34 (t, J=7 Hz, 1H), 6.94 (t, J=7 Hz, 1H), 2.43 (s, 3H). To a stirred mixture of 5-bromo 2-aminopyrimidine (8 g, 45.97 mmol) in MeOH-CH3CN (200 mL) in a steel bomb were added Pd(CH3CN)2Cl (2.38 g, 9.19 mmol), racemic-BINAP (5.7 g, 9.19 mmol), DIPEA (10.4 mL, 53.7 mmol) at room temperature and then closed the steel vessel tightly. Then CO gas (100 psi) was purged into the steel bomb and the stirring was continued at 120 C. for 45 hours. The reaction mixture was allowed to room temperature. The reaction mixture was filtered through a pad of celite. The celite pad was washed with excess of methanol and the filtrate was concentrated under vacuum. The crude material was purified by column chromatography eluting with 0.75% MeOH/DCM to afford Int-6 (5 g, 71%) as solid. Mass (m/z): 154 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 8.65 (s, 3H), 7.49 (brs, 2H), 3.58 (s, 3H) To a stirred mixture of Int-5 (3 g, 2.34 mmol) and Int-6 (1.8 g, 12.34 mmol) in 1,4-dioxane (90 mL) were added Pd(OAc)2 (279 mg, 1.23 mmol) and Xanthpos (710 mg, 1.23 mmol) followed by cesium carbonate (6 g, 18.5 mmol) at room temperature. The resulting mixture was degassed and stirred at reflux temperature for 30 hours. The reaction mixture was cooled to room temperature and then stirred for 15 minutes. The precipitated solids were filtered off, washed with water (2¡Á10 mL) and dried under vacuum. The crude material was purified by column chromatography eluting with 1.5% MeOH/DCM to afford Int-7 (0.6 g, 13.6%) as solid. Mass (m/z): 361.2 [M++1]. 1H NMR (500 MHz, dmso-d6): delta 10.76 (brs, 1H), 8.97 (s, 2H), 8.56 (d, J=7, 1H), 8.47 (d, J=5.5 Hz, 1H), 8.38 (s, 1H), 7.58 (d, J=9.5 Hz 1H), 7.34-7.29 (m, 2H), 6.99 (t, J=76 Hz, 1H), 3.84 (s, 3H), 2.46 (s, 3H). To a stirred solution of Int-7 (0.5 g, 1.38 mmol) in MeOH-CH3CN (1:2, 25 mL) was added aqueous NH2OH solution (15 mL) at 0 C. After being stirred for 20 minutes at the same temperature, NaOH (0.44 g, 11.10 mmol) in water (1 mL) was added drop wise to the reaction mixture at 0 C. The reaction mixture was warmed to room temperature and stirred for 2 days. The volatiles were concentrated under vacuum and the obtained residue was diluted with water and neutralized to about pH 7 with 2 N HCl at 0 C. The precipitated solids were filtered off, washed with water (2¡Á10 mL) and dried under vacuum to afford the title compound (0.4 g, 80%) as off-white solid. Mass (m/z): 362.1 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 11.2 (bs, 1H), 10.5 (s, 1H), 9.12 (bs, 1H), 8.84 (s, 2H), 8.57 (d, J=7.0 Hz, 1H), 8.45 (d, J=5.0 Hz, 1H), 8.38 (s, 1H), 7.58 (d, J=9.0 Hz, 1H), 7.32 (t, J=7.5 Hz, 1H), 7.25 (d, J=4.0 Hz, 1H), 6.98 (d, J=7.0 Hz, 1H), 2.49 (s, 3H). 13C NMR (125 MHz, dmso-d6): delta 160.7, 157.1, 153.0, 148.7, 144.5, 142.3, 137.9, 125.2, 123.9, 118.8, 118.2, 117.0, 116.6, 112.7, 112.4, 14.3.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,7752-82-1, 5-Bromopyrimidin-2-amine, and friends who are interested can also refer to it.

Reference:
Patent; Melvin, JR., Lawrence S.; Graupe, Michael; Venkataramani, Chandrasekar; US2010/29638; (2010); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Adding a certain compound to certain chemical reactions, such as: 4595-59-9, 5-Bromopyrimidine, 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, 4595-59-9, blongs to pyrimidines compound. 4595-59-9

Argon is bubbled for 15 minutes into a mixture of 9.3 g of tert-butyl 1-piperazinecarboxylate, 7.95 g of 5-bromopyrimidine and 6.5 g of sodium tert-butoxide in 250 ml of toluene, which is then heated at reflux, 0.277 g of palladium acetate and 1.7 ml of tri-tert-butylphosphine are added and reflux is continued for 24 hours. 0.277 g of palladium acetate is added and the mixture is heated at reflux for 8 hours. The reaction mixture is cooled to AT, water is added, the mixture is subjected to extraction with AcOEt, the organic phase is filtered and dried over Na2SO4 and the solvent is evaporated under vacuum. The residue is chromatographed on silica gel, eluting with DCM, then with a DCM/AcOEt (50/50; v/v) mixture and finally with a DCM/MeOH (95/5; v/v) mixture. This gives 3.95 g of the expected product following recrystallization from a DCM/hexane/iso ether mixture.

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; sanofi-aventis; US2005/176722; (2005); A1;,
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Pyrimidine – Wikipedia

A common compound: 504-17-6, name is 4,6-Dihydroxy-2-mercaptopyrimidine,molecular formula is C4H4N2O2S, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below., 504-17-6

General procedure: To a mixture of an aromatic aldehyde (0.25 mmol), 2-thiobarbituric acid(0.5 mmol), ammonium acetate (0.3 mmol), [H-NMP]+[HSO4]- (12 mol%)and water (2 ml) was added. Then, ultrasonic probe was directly immersed inthe resulting mixture. The progress of the reactions was monitored by TLCuntil conversion of the starting materials was satisfactory. After completion ofthe reaction, the solvent was evaporated and the precipitate was washed withEtOH and hot water to afford the pure product. All products were identified byphysical and spectroscopic data. The synthesis of the compounds 4b and 4j wasinvestigated but unfortunately even after 24 h, only a trace amount of productwas observed by TLC, that is why we could not reported the spectroscopic dataof them.

With the rapid development of chemical substances, we look forward to future research findings about 504-17-6.

Reference:
Article; Naeimi, Hossein; DIdar, Asieh; Rashid, Zahra; Zahraie, Zohreh; Journal of Antibiotics; vol. 70; 7; (2017); p. 845 – 852;,
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Pyrimidine – Wikipedia

213265-83-9 , The common heterocyclic compound, 213265-83-9, name is 4,6-Dichloro-5-fluoropyrimidine, molecular formula is C4HCl2FN2, 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.

(First Step) 4,6-Dichloro-5-fluoropyrimidine (31.8 g, content: 98.9%) and potassium carbonate (31.5 g) are initially charged in acetone (115 ml), and, at 60 C., admixed dropwise over a period of 6 hours with a solution of 44.9 g of (E)-5,6-dihydro-1,4,2-dioxazin-3-yl-(2-hydroxyphenyl)methanone O-methyloxime in 350 ml of acetone. The mixture is stirred at 60 C. for 2 hours, the acetone is distilled off, the mixture is admixed with methylene chloride and water, the organic phase is separated off, the aqueous phase is extracted with methylene chloride, the organic extracts are combined, washed with 5% NaOH and dried over sodium sulphate and the solvent is distilled off. This gives (E)-{2-[(6-chloro-5-fluoro-4-pyrimidinyl)oxy]phenyl}-(5,6-dihydro-1,4,2,-dioxazin-3-yl)methanone O-methyloxime (68.0 g, content: 95.8%, 94.5% of theory) as a solid.

According to the analysis of related databases, 213265-83-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Weintritt, Holger; Stelzer, Uwe; Gayer, Herbert; Hubsch, Walter; US2003/92723; (2003); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

504-17-6, Adding a certain compound to certain chemical reactions, such as: 504-17-6, 4,6-Dihydroxy-2-mercaptopyrimidine, 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, 504-17-6, blongs to pyrimidines compound.

General procedure: A mixture of aldehyde (1 mmoL), (thio)barbituric acid(1 mmoL) and verjuice (10 mL) was heated in an oil bath(60 C). After completion of the reaction, as monitored byTLC, using n-hexane:EtOAc (7:3) as the eluent, the reactionmixture was filtered and the precipitated product was washedwith water (3 ¡Á 10 mL) to afford the pure compound.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,504-17-6, its application will become more common.

Reference:
Article; Safari, Niloufar; Shirini, Farhad; Tajik, Hassan; Journal of the Iranian Chemical Society; vol. 16; 4; (2019); p. 887 – 897;,
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Pyrimidine – Wikipedia

302964-08-5, 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.302964-08-5, name is 2-((6-Chloro-2-methylpyrimidin-4-yl)amino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide, molecular formula is C16H13Cl2N5OS, molecular weight is 394.2783, as common compound, the synthetic route is as follows.

2-oxo-6-azaspiro [3,3] heptane oxalate (0.92 g, 0.8 mmol) was added to a solution of 2 – ((6-chloro-2-methylpyrimidin-4-yl) amino (0.3 g, 0.76 mmol) and N, N-diisopropylethylamine (0.56 mL, 1.6 mmol) of 1, 2-chloro-6-methylphenyl) 4-dioxane (10 mL) solution, heated to reflux, the reaction overnight, TLC monitoring of raw materials disappeared.The reaction was stopped at room temperature and the solvent was removed. The resulting solid was washed twice with methanol and diethyl ether and chromatographed on a white solid (20 mg, yield 6%)

Statistics shows that 302964-08-5 is playing an increasingly important role. we look forward to future research findings about 2-((6-Chloro-2-methylpyrimidin-4-yl)amino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide.

Reference:
Patent; Fudan University; Dong, Xiaochun; Zhao, WeiLi; Zhao, Yichao; Lin, Zhaohu; Lu, Xiuhong; Wang, Wen; Dong, Qian; (12 pag.)CN104151321; (2016); B;,
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