Month: May 2021

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 3438-46-8, name is 4-Methylpyrimidine. This compound has unique chemical properties. The synthetic route is as follows. name: 4-Methylpyrimidine

[0375] This reaction was conducted in the same jacketed, 49 L reactor equipped with retreat curve agitator, nitrogen purge system, bottom valve for removal of a lower portion of the contents, and Dean-Stark trap and condenser system. The reactor was first purged with nitrogen. Afterward, 20% potassium t-butoxide in THF (21.06 Kg, 37.54 mol) was charged to the reactor under N2 using a cannula system. This solution was then cooled to 0 C., and the reactor was next charged with 4-methylpyrimidine (4) (1.53 Kg, 16.27 mol) while maintaining the temperature of the reactor contents at from 0 to 5 C. Immediately afterward, the Boc-protected ethyl isonipecotate (3) prepared as shown in Part A (3.99 Kg, 15.51 mol) was charged neat over 30 minutes while continuing to maintain the reactor contents at a temperature of from 0 to 5 C. Afterward, the reactor contents were stirred for 3 hours while being maintained at 5 C. The temperature of the reactor contents was then increased to 10 C., and then maintained at that temperature for 1 hour. Subsequently, 33% aqueous acetic acid solution (6.71 Kg, 36.88 mol) was charged to the reaction mixture while maintaining the reaction mixture at below 30 C. After stirring the resulting mixture for 30 minutes, it was allowed to stand for 30 minutes. The aqueous layer was then separated. Afterward, ammonium chloride solution (2.96 Kg, 3.87 mol) was charged to the reactor. The resulting mixture was stirred for 30 minutes. After allowing the mixture to stand for 30 minutes, the aqueous layer was separated. The THF was removed from the organic remaining layer by slowly raising the batch temperature under vacuum (200 torr) until the temperature reached 60-65 C. using a distillation apparatus. The final concentrate was in the form of an amber oil. This oil and toluene (12.22 Kg, 132.6 mol) were combined in the reactor, and the resulting mixture was stirred at room temperature for 15 minutes. Afterward, water (4.01 kg, 222.5 mol) was added to the reactor, and stirring was continued for an additional 30 minutes at room temperature. The reactor contents were allowed to stand for 60 minutes. The aqueous layer was then separated. The top layer (i.e., the organic layer) was then used as is to prepare the hydrazone in Part C. [TABLE-US-00002] TABLE 2 Reaction Summary for Part B materials MW equiv. wt (kg) moles density (g/mL) volume (L) potassium t-butoxide 112.2 2.42 21.06 37.54 0.902 23.3 in THF (20%) compound (3) 257.3 1.00 3.99 15.51 1.034 3.86 compound (4) 94.11 1.05 1.53 16.27 1.031 1.48 33% acetic acid 60.05 2.40 6.71 36.88 1.049 6.4 solution 7% ammonium 53.49 0.25 2.96 3.87 chloride solution toluene 92.14 10.20 12.22 132.6 0.865 14.1 water 18.02 14.35 4.01 222.5 1.000 4.01

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it, 3438-46-8, 4-Methylpyrimidine.

Reference:
Patent; Allen, Kimberley C.; Anderson, Dennis K.; Baldus, John E.; Boehlow, Todd; Clark, Jerry D.; Dukesherer, Daniel R.; Edney, Albert D.; Fevig, Tom; Kundra, Sastry; Lawson, Jon P.; Lau, Patrick H.; McDermott, Lisa L.; Mao, Michael K.; Moe, Jodi L.; Mudipalli, Partha; Naing, Win; Selness, Shaun R.; Seymour, Christine B.; Schilke, Tobin C.; Viswanath, Shekhar; Walker, John K.; Yalamanchili, Gopichand; US2003/225108; (2003); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 1480-96-2, 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 1480-96-2 as follows.

43b2-Methoxy-5-fluorouracil (43a, 1.04g, 7.21 mmol) and N,N-dimethylaniline (1.80 mL) were heated in POCI3 at 11O0C for 90 minutes. After cooling, the reaction was added carefully to ice. The product was extracted with diethylether. The ether layer was washed with sequentially with 2N HCI, water, and brine followed by drying (MgSO4). The ether was carefully removed under reduced pressure to give 43b as a volatile liquid (0.39g, 34%) which was used without further purification. Rf = 0.26 (10% EtOAc/hexane). 1H NMR (400MHz, DMSO-d6): delta 3.91 (s, 3H), 8.79 (s, 1 H)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1480-96-2, its application will become more common.

Reference:
Patent; PFIZER INC.; WO2006/72831; (2006); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 7504-94-1, 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. 7504-94-1, name is 2-Hydrazinylpyrimidine. A new synthetic method of this compound is introduced below.

After adding 24 mg of 2-hydrazinopyrimidine and 0.030 ml of triethylamine to a 1 ml DMF solution containing 100 mg of {2-(3-hydroxymethyl-5-methoxyphenyl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene}carbamic acid methyl ester (Example (11e)), the mixture was stirred at 85 C. for 14 hours and 30 minutes under a nitrogen atmosphere. The reaction mixture was concentrated, and the residue was dissolved in 1 ml of methanol, 1 ml of THF and 0.050 ml of acetic acid. After adding 100 mg of sodium cyanotrihydroborate to the reaction mixture, it was stirred at room temperature for 21 hours and 30 minutes. The reaction mixture was crudely purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% acetic acid) to give a crude product. To a solution of the obtained crude product in 3 ml of a methanol:water:acetic acid=1:1:1 mixed solvent there was added 150 mg of iron powder, and the mixture was stirred at 60 C. for 17 hours under a nitrogen atmosphere. After filtering the reaction mixture, it was purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% acetic acid) to give the title compound (28.50 mg). 1H-NMR (CD3OD) delta 1.95 (s, 3H) 3.78 (s, 3H) 4.58 (s, 2H) 5.68 (s, 1H) 6.87 (d, J=8.8 Hz, 2H) 6.91 (s, 1H) 7.03 (s, 1H) 7.13 (s, 1H) 7.35 (t, J=4.8 Hz, 1H) 7.61 (d, J=8.8 Hz, 2H) 8.78 (d, J=4.8 Hz, 2H) Mass spectrum (ESI) m/z: 447 (M+H)+

At the same time, in my other blogs, there are other synthetic methods of this type of compound,7504-94-1, 2-Hydrazinylpyrimidine, and friends who are interested can also refer to it.

Reference:
Patent; Eisai R&D Management Co., Ltd.; US2008/15199; (2008); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 34171-40-9, Adding some certain compound to certain chemical reactions, such as: 34171-40-9, name is 2,4-Dichloro-5-ethylpyrimidine,molecular formula is C6H6Cl2N2, 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 34171-40-9.

To a mixture of 2-[[7-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazol-1-yl]methoxy]ethyltrimethylsilane (2 g, 3.57 mmol) and 2,4-dichloro-5-ethylpyrimidine (947.53 mg, 5.36 mmol) in DME (25 mL) and H2O (5 mL) was added Pd(dppf)Cl2 (261.09 mg, 357.00 umol) and K2CO3 (986.33 mg, 7.14 mmol) in one portion at 20 C under N2. The mixture was stirred at 80 C for 2 h. The mixture was poured into water (100 mL) and extracted with EA (50 mL*2). The combined organic phase was washed with brine (100 mL*2), dried with anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by silica gel chromatography (PE/EA=100/1,40/1) to give 2-[[3-(2-chloro-5-ethylpyrimidin-4-yl)-7-fluoroindazol-1-yl]methoxy]ethyltrimethylsilane (600 mg, crude) as colorless oil. LCMS: M+H+: 407.1 1.087 min (5-95% ACN in H2O, 1.5 min).

According to the analysis of related databases, 34171-40-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MARINEAU, Jason, J.; ZAHLER, Robert; CIBLAT, Stephane; WINTER, Dana, K.; KABRO, Anzhelika; ROY, Stephanie; SCHMIDT, Darby; CHUAQUI, Claudio; MALOJCIC, Goran; PIRAS, Henri; WHITMORE, Kenneth, Matthew; LUND, Kate-Iyn; SINKO, Bill; SPROTT, Kevin; (418 pag.)WO2018/13867; (2018); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 4316-98-7, Adding some certain compound to certain chemical reactions, such as: 4316-98-7, name is 6-Chloro-4,5-diaminopyrimidine,molecular formula is C4H5ClN4, 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 4316-98-7.

6B. 6-Chloro-7,9-dihydropurin-8-oneA mixture of the 5,6-diamino-4-chloropyrimidine of Example 6A (1.0 g, 6.92 mmol) and N,N’-carbonyldiimidazole (2.13 g, 13.2 mmol) in 1,4-dioxane (20 ml) was refluxed under argon for 48 hours. The solution was concentrated to a brown oil, which was triturated and washed with dichloromethane to give an off-white solid (1.02 g, 86%) LC/MS (LCTl): Rt2.45 [M+H]+ 173, 171.

According to the analysis of related databases, 4316-98-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; THE INSTITUTE OF CANCER RESEARCH:ROYAL CANCER HOSPITAL; CANCER RESEARCH TECHNOLOGY LIMITED; ASTRAZENECA AB; WO2007/125325; (2007); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 36314-97-3 ,Some common heterocyclic compound, 36314-97-3, molecular formula is C10H8ClN3, 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.

Compound 1e (13 g, 7.34 mmol) was dissolved in 300 mL of N,N-dimethylformamide and N-bromosuccinimide (12.38 g, 69.54 mmol) was added, and the reaction was stirred for 1 hour. The reaction was stopped, the reaction solution was poured into 1 L of water, stirred for 20 minutes, filtered, and the filter cake was dried.The crude title compound 2a (18 g) was obtained, which was used for the next step without purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,36314-97-3, its application will become more common.

Reference:
Patent; Jiangsu Hengrui Pharmaceutical Co., Ltd.; Shanghai Hengrui Pharmaceutical Co., Ltd.; Lu Biao; Wang Shenglan; Shen Xiaodong; He Feng; Tao Weikang; (56 pag.)CN109535161; (2019); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Electric Literature of 61044-96-0, 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 61044-96-0, name is 4-Chloro-5-methyl-2-(methylthio)pyrimidine. This compound has unique chemical properties. The synthetic route is as follows.

A microwave vial is charged with 4-chloro-5-methyl-2-methylsulfanylpyrimidine (174 mg, 1 mmol), 10-oxa-tricyclo[5.2.1.0*2,6*]decane-3,5-dione (166 mg, 1 mmol), palladium acetate (12 mg, 0.05 mmol), X-Phos (48 mg, 0.1 mmol) and potassium phosphate (424 mg, 2 mmol). 1 ,2-dimethoxyethane (3 ml) is added and the reaction heated to 160 0C, with stirring, for 30 minutes. Silica gel is added to the crude reaction mixture, the solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel to give 4-(5-methyl-2-methylsulfanyl-pyrimidin-4-yl)-10-oxa-tricyclo[5.2.1.0*2,6*]decane-3,5- dione (34 mg).

According to the analysis of related databases, 61044-96-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SYNGENTA LIMITED; WO2009/30450; (2009); A2;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of 65996-58-9, 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.65996-58-9, name is 2-Amino-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one, molecular formula is C6H6N4O, molecular weight is 150.14, as common compound, the synthetic route is as follows.

To a suspension of 2-amino-SH-pyrrolo [3, [2-D] PYRIMIDIN-4 (3H)-ONE] (9- deazaguanine) (0.454 g, 3.0 mmol) (prepared according to J. Org. Chem. 1978,43, 2536) and 2-O-methyl-1, 3, [5-TRI-O-BENZOYL-D-D-RIBOFURANOSE] (1.54 g, 3.2 mmol) in dry nitromethane (23 mL) at [60C] was added stannic chloride (0.54 mL, 4.5 mmol). The reaction mixture was maintained at this temperature for 0.5 hr. , cooled and poured onto ice-cold saturated sodium bicarbonate solution (70 mL). The insoluble material was filtered through florisil and washed with ethyl acetate [(3X50] mL). The filtrate was extracted with ethyl acetate [(2X50] mL), and organic layer was washed with water [(2X50] mL), dried over [NA2SO4] and evaporated to dryness. Chromatography of the resulting foam on silica gel with [CH2CI2/MEOH] (14: 1) afforded the benzoylated product (0.419 g, 30% yield). To a suspension of the benzoylated product (0.25 g) in MeOH (2.4 mL) was added t-butylamine (0.52 [ML)] and stirring at room temperature was continued for 24 hrs. followed by addition of more t-butylamine [(0. 2] mL). The reaction mixture was stirred at ambient temperature overnight, concentrated in vacuum and the residue was purified by flash chromatography over silica gel using CH2Cl2/MeOH (85: 15) as eluent giving the desired compound as a foam (0.80 g). ‘H NMR [(200MHZ,] [DMSO-D6)] : [3] Hz3.28 (s, 3H), 3.40-3. 52 (m, 3H), 3.87-3. 90 (m, 1H), 4.08-4. 09 (m, 1H), 4.67 (d, 1H, J = 5.2 Hz), 4.74 (d, 1H, J = 7.0 Hz), 5.62 and 5.50 (2 bs, 3H), 7.14 (d, 1H, [J=] 2.6 Hz), 10.43 (s, [LH),] 11.38 (s, [LH)] ; Mass spectrum: calcd. for C12H16N4O5: 296. 28; found: 295.11.

The chemical industry reduces the impact on the environment during synthesis 65996-58-9, I believe this compound will play a more active role in future production and life.

Reference:
Patent; ISIS PHARMACEUTICALS, INC.; WO2003/99840; (2003); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 144927-57-1, 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.144927-57-1, name is Ethyl 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate, molecular formula is C9H8ClN3O2, molecular weight is 225.6317, as common compound, the synthetic route is as follows.

Ethyl 4-chloro-7H-pyrrolo[2,3-^pyrimidine-5-carboxylate (50.0 mg, 0.222 mmol), phenyl boronic acid (32.4 mg, 0.266 mmol) and potassium carbonate (0.332 mL, 0.665 mmol) were added to tetrahydrofuran (1.5 mL) in a microwave vial. The solution was purged with nitrogen for 5 minutes and PdCl2(dppf)-CH2Cl2 (18 mg, 0.022 mmol) was then added. The reaction was sealed and heated at 125 C by microwave irradiation for 30 minutes. The reaction mixture was diluted with EtOAc and washed with saturated sodium bicarbonate, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of desired product was carried out by reverse phase HPLC using an acetonitrile gradient in water with 0.1% TFA modifier. Pure fractions were pooled and concentrated under reduced pressure. Saturated aqueous sodium bicarbonate and EtOAc were added to the residue. The organic layer was separated and the aqueous layer was then extracted with EtOAc (x3). The combined organic layers were then washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford the product as a solid. LRMS (ESI) calc’d for C15Hi4ClN302 [M+H]+: 268, found268. 1H NMR (600 MHz, DMSO-D6) delta 13.01 (s, 1H), 8.91 (s, 1H), 8.30 (s, 1H), 7.63 (m, 2H), 7.49 (m, 3H), 3.82 (q, 2H, J= 7.04 Hz), 0.78 (t, 3H, J= 7.04 Hz).

The chemical industry reduces the impact on the environment during synthesis 144927-57-1, I believe this compound will play a more active role in future production and life.

Reference:
Patent; MERCK SHARP & DOHME CORP.; AHEARN, Sean, P.; CHRISTOPHER, Matthew; JUNG, Joon; PU, Qinglin; RIVKIN, Alexey; SCOTT, Mark, E.; WITTER, David, J.; WOO, Hyun Chong; CASH, Brandon; DINSMORE, Christopher; GUERIN, David; WO2013/85802; (2013); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 10132-07-7 ,Some common heterocyclic compound, 10132-07-7, molecular formula is C4H3Cl2N3, 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 3-cyanobenzylaldehyde (1.0 g) and N-cyclohexyl-1,3-propane-diamine (2.4 g) in CH3OH (150 mL) was heated to 60 C. for 18 hours. After cooling to room temperature, NaBH4 (1.5 g) was slowly added to the above solution. The mixture was stirred for another 30 minutes. The mixture was then concentrated, quenched with NH4Cl (aq), and extracted with CH2Cl2. The organic layers were combined, dried with anhydrous MgSO4, and concentrated to give a residue. The residue was purified by chromatography on silica gel (EtOAc/Et3N=7/3) to afford Intermediate 201-I (1.6 g) in a 80% yield. A solution of Intermediate 201-I (1.6 g) and Boc2O (3.5 g) in CH2Cl2 (160 ml) was stirred at 25 C. for 15 hours and then concentrated. The resultant residue was purified by chromatography on silica gel (EtOAc/Hexane=1/1) to afford Intermediate 201-II as a yellow oil (2.36 g) in a 85% yield. A solution of Intermediate 201-II and LiAlH4 (2.3 g) in THF (230 mL) was stirred at 0 C. for 4 hours. After Na2SO4110H2O was added, the solution was stirred at room temperature for 0.5 hour. The solution was then filtered through a celite pad. The filtrate was dried over anhydrous MgSO4 and concentrated to give a residue. The residue was purified by column chromatography on silica gel (using MeOH as an eluant) to afford Intermediate 201-III (1.1 g) in a 50% yield. Diisopropylethylamine (1.1 mL) was added to a solution of 2,4-dichloro-6-aminopiperidine (0.41 g) and Intermediate 201-III (1.1 g) in 1-pentanol (10 mL). The reaction mixture was stirred overnight at 120 C. The solvent was removed under vacuum and the residue was purified by column chromatography on silica gel (EtOAc/Hexane=3/7) to afford 201-IV (1.0 g) in a 65% yield. To a solution of Intermediate 201-IV (1.0 g) in 1-pentanol (1 mL) was added N1-hydroxyethoxyethyl piperazine (0.25 g). After the solution was stirred at 120 C. for 8 hours, it was concentrated. The residue thus obtained was purified by column chromatography on silica gel (EtOAc/MeOH=4/1) to afford Intermediate 201-V (730 mg) in a 60% yield. A solution of 20% TFA/CH2Cl2 (5 mL) was added to a solution of Intermediate 201-V (0.73 g) in CH2Cl2 (2 mL). The reaction mixture was stirred for 5 hours at room temperature and concentrated by removing the solvent. The resultant residue was purified by column chromatography on silica gel (21% NH3 (aq)/MeOH=1/19) to afford Compound 201 (434 mg) in a 85% yield. Compound 201 was then treated with 1 M HCl (4 mL) in CH2Cl2 (2 mL) for 0.5 hour. After the solvents were removed, the residue was treated with ether and filtered to give hydrochloride salt of compound 201. CI-MS (M++1): 541.3.

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. 10132-07-7, 4-Amino-2,6-dichloropyrimidine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Yen, Chi-Feng; Hu, Cheng-Kung; Chou, Ming-Chen; Tseng, Chen-Tso; Wu, Chien-Huang; Huang, Ying-Huey; Chen, Shu-Jen; King, Chi-Hsin Richard; US2006/281712; (2006); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia