Pyrimidines

36315-01-2 , The common heterocyclic compound, 36315-01-2, name is 2-Amino-4,6-dimethoxypyrimidine, molecular formula is C6H9N3O2, 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.

REFERENTIAL EXAMPLE 1 Preparation of 2-chloro-4,6-dimethoxypyrimidine 1,260 ml of 36% hydrochloric acid were charged in a 5-l four-necked flask and then cooled to 0 C. After 180 g (1.16 moles) of 2-amino-4,6-dimethoxypyrimidine were added in small portions into the flask, the resulting mixture was stirred for about 1 hour until the reaction mixture changed into a syrupy form. After the reaction mixture was cooled to -15 C., 260 ml of 159 g (2.3 moles) of NaNO2 in H2 O were added dropwise over about 1 hour under vigorous stirring. After completion of the dropwise addition, the resulting mixture was stirred at -15 to -10 C. for additional 1 hour so that the reaction was brought to completion. While the reaction mixture was retained at -5 C., 1.5 l of a 30% aqueous solution of NaOH were charged dropwise so that the reaction mixture was neutralized to pH 7. By filtration under reduced pressure, a clay-like material of a purple color was collected. The target compound was extracted from the clay-like material using 3 l of ethyl acetate. Through the procedures of washing with water, drying over anhydrous sodium sulfate and removal of the solvent, 63 g of bluish crude crystals were obtained. They were crystallized further by silica gel chromatography to obtain 60.8 g of white crystals (yield: 29.9%). Melting point: 101.5-102.5 C.

According to the analysis of related databases, 36315-01-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Mitsui Toatsu Chemicals, Incorporated; US4986846; (1991); A;,
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1193-24-4, 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 1193-24-4 as follows.

Example 2; To a 1000 mL four-neck flask, 89.7 g of 4,6-dihydroxypyrimidine and 179.3 g of chlorobenzene were added. The obtained mixture was adjusted at 40C, and then, 129.6 g of sulfuryl chloride was added dropwise thereto over 1 hour. The obtained mixture was maintained at the same temperature for 6 hours. To the obtained reaction mixture, 269.9 g of phosphorus oxychloride was added at the same temperature. Further, 178.1 g of triethylamine was added dropwise thereto over 2 hours at an inner temperature of 40 to 80C. After completion of the addition, the obtained mixture was maintained at 83C for 10 hours. The obtained reaction mixture was cooled to room temperature. To another 100 mL four-neck flask, 269.0 g of water was added followed by adjusting at 40C. To it, the obtained reaction mixture was added dropwise over 30 minutes. The inner temperature during the addition was 30 to 50C. The obtained mixture was filtrated using Radiolite (registered trademark) and the obtained filtrate was separated to an organic layer and an aqueous layer. The aqueous layer was extracted with 44.8 g of chlorobenzene, and the obtained chlorobenzene layer was mixed with the previously obtained organic layer. The organic layer after mixing was washed with 44.8 g of water and then, concentrated under reduced pressure to obtain 169.2 g of black oily matter. The oily matter was analyzed by high performance liquid chromatography internal standard method, and 126.9 g of 4,5,6-trichlorpyrimidine was containd in the oily matter. The yield was 86%.

The chemical industry reduces the impact on the environment during synthesis 1193-24-4, I believe this compound will play a more active role in future production and life.

Reference:
Patent; Sumitomo Chemical Company, Limited; EP2128141; (2009); A1;,
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2380-63-4, 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 2380-63-4, name is 1H-Pyrazolo[3,4-d]pyrimidin-4-amine. This compound has unique chemical properties. The synthetic route is as follows.

The A10.7g (5.2mmol), bromocyclopentane 1.55g (10.4mmol, 2eq.) And cesium carbonate 3.39g (10.4mmol, 2eq.), In 12mL DMF solution, 110 deg.] C overnight, was concentrated acetic acid ethyl, dried, Biotage silica gel column chromatography (dichloromethane / methanol = 1%) to give a pale yellow solid A90.84g, yield 80%.

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 2380-63-4, 1H-Pyrazolo[3,4-d]pyrimidin-4-amine.

Reference:
Patent; Nanjing Yong Shan Biological Technology Co., Ltd.; Wang Yazhou; Jin Qiu; Tang Feng; Huang Wei; Hua Yulin; (10 pag.)CN103113375; (2017); B;,
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7226-23-5, A common compound: 7226-23-5, name is 1,3-Dimethyltetrahydropyrimidin-2(1H)-one,molecular formula is C6H12N2O, 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.

A solution of diisopropylamine (951 muL, 6.79 mmol) in dry tetrahydrofuran (6 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (2 mL) was cooled to -78 C. under nitrogen and then treated with a 2.5M solution of n-butyllithium in hexanes (2.5 mL, 6.79 mmol). The resulting reaction mixture was stirred at -78 C. for 30 min and then treated dropwise with a solution of (3,4-bis-methanesulfonyl-phenyl)-acetic acid methyl ester (1.89 g, 6.17 mmol) in dry tetrahydrofuran (12 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (4 mL). The resulting reaction mixture was allowed to stir at -78 C. for 1 h, at which time, a solution of iodomethylcyclopentane (1.56 g, 7.40 mmol) in a small amount of dry tetrahydrofuran was added dropwise. The reaction mixture was allowed to warm to 25 C. where it was stirred for 64 h. The reaction mixture was quenched with water (150 mL) and then concentrated in vacuo to remove tetrahydrofuran. The remaining residue was further diluted with water (100 mL) and then extracted with ethyl acetate (1*250 mL). The organic layer was washed with a saturated aqueous sodium chloride solution (1*100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 3/1 hexanes/ethyl acetate) afforded 2-(3,4-bis-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid methyl ester (1.61 g, 67%) as a yellow oil: EI-HRMS m/e calcd for C17H24O6S2 (M+) 388.1014, found 388.1014.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 7226-23-5.

Reference:
Patent; Bizzarro, Fred Thomas; Corbett, Wendy Lea; Grippo, Joseph Francis; Haynes, Nancy-Ellen; Holland, George William; Kester, Robert Francis; Sarabu, Ramakanth; US2001/39344; (2001); A1;; ; Patent; Hoffman-La Roche Inc.; US6610846; (2003); B1;,
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591-55-9, 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. 591-55-9, name is 5-Aminopyrimidine. A new synthetic method of this compound is introduced below.

To a solution of pyrimidin-5-amine (95.1 mg, 1.00 mmol) and N,N-diisopropylethylamine (175 mg, 1.35 mmol) in tetrahydrofuran (3 mL) at room temperature, was added a solution of ditrichloromethyl carbonate (101 mg, 0.34 mmol) in THF (3 mL) dropwise. After stirring for 15 min, triethylamine (152 mg, 1.50 mmol) and 1-[3-amino-4-[bis(2-methylpropyl)amino]phenyl]cyclobutane-1-carboxylic acid (80 mg, 0.25 mmol) was added. The resulting mixture was stirred at room temperature for another 2 h. The reaction was then concentrated under vacuum. The residue was purified by Prep-HPLC with the following conditions: [Column: X bridge, C18, 19*50mm; Mobile Phase, H2O (0.05% NH4HCO3)/MeCN, 35% – 55% in 8 min; Rate: 25 mL/ min; Detector, 254 nm] to afford the desired product (72.7 mg, 17% yield) of as a white solid. LCMS (ES, m/z): 440.5 [M+H]+. 1H NMR (300 MHz, DMSO-d6, ppm): delta 10.01 (s, 1 H), 8.93 (s, 2 H), 8.81 (s, 1H), 8.20 (s, 1H), 7.90 (d, = 2.1 Hz, 1 H), 7.19 (d, J= 8.3 Hz, 1 H), 6.92 (dd, J= 8.3, 2.2 Hz, 1 H), 2.68 (d, J= 6.9 Hz, 6 H), 2.42-2.26 (m, 2 H), 1.94-1.50 (m, 4 H), 0.86 (d, J= 6.5 Hz, 12 H).

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. 591-55-9, 5-Aminopyrimidine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; INVENTISBIO INC.; DAI, Xing; WANG, Yaolin; (187 pag.)WO2017/139414; (2017); 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 stirred solution of 5-bromopyrimidin-2-amine(A39, 1.0 g, 5.74 mmol) in DMF (20 mL) was added ethyl 3-bromo pyruvate(A15, 0.86 mL, 6.89 mmol) . The reaction mixture was Stirred for 16 h at Room temp and then concentrated under reduced pressure. The crude product was triturated with water and washed with n-pentane and dried to afford ethyl 6-bromoimidazo[l,2-a]pyrimidine-2-carboxylate A40 as light brown solid Yield: 1.50 g,(87%). LC-MS m/z : 268.20[M-H]

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; JUBILANT BIOSYS LIMITED; VADIVELU, Saravanan; RAJAGOPAL, Sridharan; BURRI, Raghunadha Reddy; GARAPATY, Shivani; SIVANANDHAN, Dhanalakshmi; THAKUR, Manish Kumar; NATARAJAN, Tamizharasan; SWAMY, Indu N; NAGARAJU, Nagendra; KANAGARAJ, Subramaniam; MOHD, Zainuddin; SARKAR, Sayantani; SAMANTA, Swapan Kumar; ., Hariprakash; (284 pag.)WO2019/102494; (2019); A1;,
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1500-85-2, A common compound: 1500-85-2, name is 7H-Pyrrolo[2,3-d]pyrimidin-4-amine,molecular formula is C6H6N4, 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.

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%;

With the rapid development of chemical substances, we look forward to future research findings about 1500-85-2.

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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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.5909-24-0, name is Ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate, molecular formula is C8H9ClN2O2S, molecular weight is 232.6873, as common compound, the synthetic route is as follows.5909-24-0

[4-C hlor o-2-(methylthio)pyrimidin-5-yl] methanol. 4-Chloro-2-methylsulfanyl-5-pyrimidinecarboxylate ethyl ester (62 g, 260 mmol) was dissolved in anhydrous tetrahydrofuran (500 mL) in a 3-necked 5L round bottomed flask fitted with a mechanical stirrer, addition funnel, temperature probe and nitrogen inlet. The solution was cooled to 0C. Diisobutylaluminum hydride in tetrahydrofuran (1M solution, 800 mL) was added dropwise over a period of 2 hours. After the addition was complete, the reaction mixture was kept at 0C for 0.5 hours. The reaction was quenched at 0C by the slow addition of saturated aqueous sodium sulfate (265.3 mL, 530.7 mmol) keeping the internal reaction temperature below 10C. Ethyl acetate (900 mL) was added and the reaction slowly warmed to room temperature overnight. 6M HC1 was added till the reaction mixture was slightly acidic (pH 6). The reaction mixture was filtered thru a pad of Celite and the aluminum salts were washed with ethyl acetate (1L). The filtrate was poured into a separatory funnel and washed twice with water (600 mL) and finally with brine (600 mL). The organic layer was dried over sodium sulfate, filtered thru Celite and the solvent concentrated in vacuo to afford 39.2g (77% crude yield) of a dark yellow oil. The material was used as is for the next step. NMR (CDCI3) delta 8.56 (s, 1H), 4.76 (s, 2H), 2.59 (s, 3H); MS (ESI+) for C6H7C1N20S m/z 191.0 (M+H)+ .

Statistics shows that 5909-24-0 is playing an increasingly important role. we look forward to future research findings about Ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate.

Reference:
Patent; G1 THERAPEUTICS, INC.; STRUM, Jay, Copeland; BISI, John, Emerson; ROBERTS, Patrick, Joseph; GASTON, Ricky, D.; GADWOOD, Robert, C.; WO2015/161287; (2015); A1;,
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A common compound: 213265-83-9, name is 4,6-Dichloro-5-fluoropyrimidine,molecular formula is C4HCl2FN2, 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., 213265-83-9

Into 3 ml of acetnitrile were added 0.2 g of 4, 6-DICHLORO-5-FLUOROPYRIMIDINE, 0.50 g of pottasium carbonate and 0.27 g of cis-2, 6-DLMETHYLHEXAHYDRO-LH-AZEPINE hydrochloride, and the mixture was stirred for 2 hours at 60 C. The reaction mixture was cooled to near room temperature, a saturated ammonium chloride aqueous solution was added therein, and the mixture was extracted with tert-butyl methyl ether three times. The organic layers were washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to obtain 0.3 g of 1- (6-CHLORO- 5-fluoropyrimidin-4-yl) -cis-2, 6-DIMETHYLHEXAHYDRO-LH-AZEPINE H-NMR : 0.90-1. 04 (m, 4H involving a doublet at 0.95), 1.10-1. 32 (m, 4H), 1.36-1. 48 (m, 1H), 1.71-1. 90 (m, 3H), 2.04-2. 14 (M, 1H), 2.91 (brt, 1H), 3.70 (brs, 1H), 4.42-4. 82 (br, 1H) 8.09 (d, 1H) GC-MS: 257 (M+)

With the rapid development of chemical substances, we look forward to future research findings about 213265-83-9.

Reference:
Patent; SUMITOMO CHEMICAL COMPANY, LIMITED; WO2004/99160; (2004); A1;,
Pyrimidine | C4H4N2 – PubChem,
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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 147118-37-4, name is N-(4-(4-Fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide. This compound has unique chemical properties. The synthetic route is as follows. 147118-37-4

Methyl magnesium chloride solution (3M) (11.87 ml, 0.0356 moles) in tetrahydrofuran was added to a pre-cooled suspension of pyrimidine carboxaldehyde (5 g, 0.0142 moles) in anhydrous tetrahydrofuran (30 ml) under stirring for 30 min at 0-5 C. The reaction mass was stirred at the same temperature. After completion of the reaction, the reaction mass was poured into pre-cooled saturated ammonium chloride solution (100 ml) at 0-5 C. and stirred for 1 h at 5-10 C. The product was extracted into ethyl acetate (150 ml) and washed with saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was distilled under vacuum at 40-45 C. until the traces of ethyl acetate were completely removed to give the title compound.

Statistics shows that 147118-37-4 is playing an increasingly important role. we look forward to future research findings about N-(4-(4-Fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide.

Reference:
Patent; Mallela, Sambhu Prasad Sarma; Nandi, Sakumar; Nangi, Gangadhara Bhima Shankar; Ananta, Rani; Meenakshiunderam, Sivakumaran; US2011/178296; (2011); A1;,
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