Month: August 2021

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.131860-97-4, name is (E)-Methyl 2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)-3-methoxyacrylate, molecular formula is C15H13ClN2O4, molecular weight is 320.73, as common compound, the synthetic route is as follows.Safety of (E)-Methyl 2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)-3-methoxyacrylate

To a solution of methyl (E)-2-{2-[6-chloropyrimidin~4-yloxy]phenyl} -3-methoxyacrylate (64.4g; prepared as described in WO 92/08703) in cyclohexanone (approximately 80g) was added 2-cyanophenol (26.6g) and cyclohexanone (26.6g). The mixture was heated to 5O0C and DABCO (0.2g) in cyclohexanone (2g) and potassium carbonate (42.4g) were charged. The reaction was heated to 9O0C and held for three hours. The temperature was adjusted to 50-600C and hot water (88g) added, stirred for 15 minutes, and the aqueous phase separated. Analysis of the cyclohexanone layer gave a 91.3% yield of methyl (E)- 2-{2-[6-(2- cyanophenoxy)pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate (azoxystrobin). Cyclohexanone was removed by vacuum distillation, and to the distillation residues at 8O0C was added methanol (59g). The methanol solution was cooled slowly to 0-50C, filtered and the cake washed with methanol (2×15.8g) to give, after drying, methyl (E)- 2-{2-[6-(2- cyanophenoxy)pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate (87.0% yield).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,131860-97-4, (E)-Methyl 2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)-3-methoxyacrylate, and friends who are interested can also refer to it.

Reference:
Patent; SYNGENTA LIMITED; WO2006/114572; (2006); A2;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

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. 49844-90-8, name is 4-Chloro-2-(methylthio)pyrimidine, molecular formula is C5H5ClN2S, 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. Application In Synthesis of 4-Chloro-2-(methylthio)pyrimidine

A mixture of 4-chloro-2-(methylthio)pyrimidine (102.6 g, 0.639 mol), 3-phenyl-1H-pyrazole-4-carbaldehyde (100.0 g, 0.581 mol), potassium carbonate (160.5 g, 1.162 mol), and dimethylformamide (700 mL) was stirred at 40-50 for 2 hours. Purified water (1.6 L) was slowly added to the reaction mixture, which was then stirred at room temperature for 2 hours. The resulting solid was filtered and then driedinvacuoto obtain 154.0 g of the titled compound. (Yield: 89.5%[78]1H-NMR(400MHz, CDCl3) delta 10.10(s, 1H), 9.20(s,1H), 8.65(d, 1H), 7.84-7.86(m, 2H), 7.67-7.71(m, 3H), 2.65(s, 3H)

With the rapid development of chemical substances, we look forward to future research findings about 49844-90-8.

Reference:
Patent; YUHAN CORPORATION; OH, Sang-Ho; KHOO, Ja-Heouk; LIM, Jong-Chul; LEE, Doo-Byung; LEE, Jung-Ae; LEE, Jun-Sup; JU, Hyun; SHIN, Woo-Seob; JEON, Sang-Seol; (24 pag.)WO2019/22486; (2019); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 22536-66-9 ,Some common heterocyclic compound, 22536-66-9, molecular formula is C5H4ClN3O, 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.

Example 261 N-[10,ll-dimethyl-4-oxo-3-(trifluoromethyl)-2,5,7-triazatricyclo[6.4.0.02’6]dodeca- l(12),6,8,10-tetraen-3-yl]-2-[(2-methoxyethyl)amino]pyrimidine-4-carboxamide (ABR 239626) To a stirred solution of 2-chloropyrimidine-4-carboxamide, available via a literature method: PCT Int. AppL, 2001068612 (330 mg, 2.08 mmol) in DMF (6 mL) was added methyl 3,3,3- trifiuoro-2-oxopropanoate (355 mu, 3.47 mmol) followed by pyridine (170 mu, 2.08 mmol) under nitrogen. The reaction was stirred at room temperature for 2 h. Thionyl chloride (150 mu, 2.08 mmol) was added at 0C. The reaction was stirred for 1 h at 0C and then concentrated. The residue was filtered through a short pad of silica, eluting with DCM, under nitrogen. The filtrate was concentrated, and the acyl intermediate that remained was dissolved in DMF (5 mL) under nitrogen. The solution of acyl intermediate was added to a solution of 5,6-dimethyl-lH-l ,3- benzodiazol-2 -amine (280 mg, 1.74 mmol) in DMF (8 mL) followed by triethylamine (280 2.08 mmol). The reaction mixture was stirred for a further 16 h and then concentrated. The residue was dissolved in EtOAc (50 mL) and washed with water (3 x 50 mL) and brine (2 x 50 mL) and then dried (MgSO_i), filtered and concentrated to afford 2-chloro-N-[10,l 1 -dimethyl-4- oxo-3-(trifluoromethyl)-2,5,7-triazatricyclo[6.4.0.02,6]dodeca-l(12),6,8,10-tetraen-3- yl]pyrimidine-4-carboxamide. (260 mg, 15%). m/z = 424.95 (MH)+. A sealable tube was charged with a portion of 2-chloro-N-[10,l 1 -dimethyl-4-oxo-3- (trifluoromethyl)-2,5,7-triazatricyclo[6.4.0.02,6]dodeca-l(12),6,8,10-tetraen-3-yl]pyrimidine-4- carboxamide (250 mg, 0.35 mmol), 2-methoxyethan- 1 -amine (92 muL·, 1.06 mmol), K2C03 (150 mg, 1.06 mmol) and DMF (5 mL). The tube was flushed with nitrogen, sealed and stirred at 100C for 6 h. Then reaction mixture was concentrated and the resulting residue was diluted with EtOAc (20 mL) and water (20 mL). The aqueous phase was extracted with EtOAc (2 x 10 mL). The combined organic extracts were washed with 10 % citric acid (aq) (2 x 20 mL) and brine (20 mL) and then dried (MgS04), filtered and concentrated. The crude product was purified by automated reverse phase HPLC (low pH Method A) to afford the title compound as a white solid (50 mg, 31 %).

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. 22536-66-9, 2-Chloropyrimidine-4-carboxamide, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ACTIVE BIOTECH AB; WELLMAR, Ulf; LIBERG, David; EKBLAD, Maria; BAINBRIDGE, Marie; EAST, Stephen; HARGRAVE, Jonathan; PREVOST, Natacha; WO2015/177367; (2015); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 696-82-2, 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 696-82-2, name is 2,4,6-Trifluoropyrimidine. This compound has unique chemical properties. The synthetic route is as follows.

(1) 34.1 parts of H acid was dissolved in 200 parts of water,Add 10% sodium carbonate solution to adjust the pH to 7,Total dissolved, then 13.5 parts of trifluoropyrimidine at 20 C,Condensed at pH 5 for 3 to 4 hours,No H acid when the end point, obtained condensation products; (2) take 12.3 parts of para-amino-anisidine diazonium salt, and the condensation product obtained in step (1) at 15 C, a pH of 6Under the conditions of coupling reaction 5h, to give compound A.

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 696-82-2, 2,4,6-Trifluoropyrimidine.

Reference:
Patent; Jiangsu Demeike Chemical Co., Ltd.; Wang Xiaojun; (7 pag.)CN106398303; (2017); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 308348-93-8, 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.308348-93-8, name is Methyl 2-aminopyrimidine-5-carboxylate, molecular formula is C6H7N3O2, molecular weight is 153.14, as common compound, the synthetic route is as follows.

Methyl 2-aminopyrimidine-5-carboxylate (300 mg, 2.0 mmol) was diluted in methanol (5 ml_) containing a few drops of water. Lithium hydroxide (122 mg, 5.1 mmol) was added, and the reaction mixture was stirred at 60 0C overnight. The mixture was concentrated under reduced pressure, then diluted in water and adjusted to pH 4 with 1 M HCI. 2- Aminopyrimidine-5-carboxylic acid precipitated as a white solid, which was isolated by vacuum filtration (244 mg, 90%): 1H NMR (DMSO-c/6) delta: 12.73 (1 H, br s), 8.63 (2H, s), 7.44 (2H, br s).

The chemical industry reduces the impact on the environment during synthesis 308348-93-8, I believe this compound will play a more active role in future production and life.

Reference:
Patent; BAYER PHARMACEUTICALS CORPORATION; WO2008/70150; (2008); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 130049-82-0, Adding some certain compound to certain chemical reactions, such as: 130049-82-0, name is 3-(2-Chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidine-4-one,molecular formula is C11H15ClN2O2, 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 130049-82-0.

Into a clean 2L, three-necked RB flask equipped with shaft, condenser, and thermo socket was charged 600 ml of DMF, lOOg (0.404 moles) of 3-(2-Chloroethyl)-6,7,8,9- tetrahydro-9-hydroxy-4H-pyrido[l52-a]pyrimidin-4-one of formula- VI obtained from Example 5, 67.19g (0.404 moles) of potassium iodide, 111.91g (0.808moles) of potassium, carbonate and 103.68g (0.404 moles) of 6- fluoro-3-(4- piperidinyl)-l,2- benzisoxazole HCl (formula-VII). The reaction mass was heated to 60-650C and maintained for 18h. Reaction mass was cooled to 25-300C, stirred for Ih and filtered under vacuum. The wet cake was washed with 200ml of DMF. The wet cake was leached with 2 x 500ml of water and 1 x 500ml of methanol. The wet material was dried in the oven at 70-750C for Ih to yield 114g of technical grade paliperidone. Above technical grade paliperidone was recrystallized from methanol via charcoal treatment to get 6Og (34.74% yield) of pure paliperidone. Purity by HPLC is > 99.8%.S Alternatively technical grade paliperidone was purified by the following chemical method.Above technical grade paliperidone (114g) was dissolved in 6.84L of methanol at 65- 7O0C. Charcoal (20 g) was added to the resultant solution and filtered under vacuum using a filter aid. The solvent was distilled of from the filtrate at 60-650C using0 rotavapor under vacuum to get a cream colored solid. Methanol (575 ml) was added to the solid and stirred for 45min at 25-300C. The reaction mass was filtered and dried in an oven at 70-750C to get 90 g of paliperidone.Into a clean and dry IL, three-necked RB flask equipped with shaft, thermo socket,5 addition funnel and stopper was charged 57.0 ml of cone. HCl and 570 ml of water.The reaction mass was stirred for 5min and charged the above solid (9Og). The reaction mass was stirred for 5-10min at 25-300C to get yellow colored clear liquid. pH of the reaction mass was adjusted to 6.0 to 6.5 by dropwise addition of dilute(concentrated aq ammonia solution was diluted with equal volume of water) aq.0 ammonia solution. The reaction mass was stirred for 30min and filtered under vacuum. The wet solid was dried in the oven at 70-750C to get 88g of paliperidoneHCl.Above solid was transferred taken into a IL RB flask containing 570 ml of methanol.5 The suspension was stirred for 30min at 25-3O0C, filtered under vacuum and dried in the oven at 70-750C for Ih to get 85 g pure paliperidone HCl. HPLC purity is > 99.80%.Above paliperidone HCl salt (85.0 g) and 2280 ml of water were suspended in a RB0 flask at 25-300C. pH was adjusted to 8.5 to 9.0 by adding aq. potassium carbonate solution (prepared from 57 g of potassium carbonate and 570 ml of water). The resultant cream-colored suspension was stirred for 30 min at 25-300C and filtered under vacuum. The wet cake was washed with 1500ml of water followed by 300ml of methanol. The wet cake was triturated with 450 ml of methanol for 30 min and filtered. Paliperidone was dried in vacuum oven at 65-70C for 4h to afford 59 g (34.33%) of pure paliperidone. Purity by HPLC is > 99.8%. 1H-NMR (CDCl3): 1.75 (m, 2H, aliphatic-H), 1.95 (m, IH, aliphatic-H), 2.15 (m, 5H, aliphatic-H), 2.24 -2.40 (m, 5H, aliphatic-H), 2.56 (t, 2H, -CH2-, J = 6.84 Hz), 2.76 (t, 2H, -CH2-, J = 7.82 Hz), 3.09 (m, IH, aliphatic-H), 3.18 (d, 2H, aliphatic-H, J =11.72 Hz), 3.92 (m, 2H, aliphatic-H), 4.15 (s, IH, -OH, D2O exchangeable), 4.50 (dd, IH, aliphatic-H J = 3.91 Hz), 7.07 (m, IH, aromatic-H), 7.23 (m, IH aromatic-H), 7.70 (dd, IH, aromatic-H, J= 2.93 Hz).

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. 130049-82-0, 3-(2-Chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidine-4-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; NATCO PHARMA LIMITED; WO2009/10988; (2009); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 5018-38-2, 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. 5018-38-2, name is 4,6-Dichloro-5-methoxypyrimidine, molecular formula is C5H4Cl2N2O, 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.

Example 3: Preparation of 6-chloro-N-[2-[2-fluoro-4-[[4-(trifluoromethyl)-2-pyridyl] oxy]phenyl]ethyl]-5-methoxy-pyrimidin-4-amine (V-14) To a solution of 2-[2-fluoro-4-[[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]ethanamine hydrochloride (344 mg, 0.9 mmol) in NMP (5 ml.) was added diisopropylethylamine (0.36 mL, 2.1 mmol). The solution was stirred for 5 min at room temperature at which time 4,6-dichloro-5-methoxypyrimidine (150 mg, 0.8 mmol) was added. The reaction mixture was stirred at 80C overnight then allowed to cool to room temperature. Water was added and was extracted with MTBE (3x). The combined organic layers were washed with water, dried over Na2S04, and concentrated in vacuo. The residue was purified by flash silica column chromatography to provide 288 mg (0.65 mmol, 78%) of the light yellow oily product.

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 5018-38-2, 4,6-Dichloro-5-methoxypyrimidine.

Reference:
Patent; BASF SE; BASF SCHWEIZ AG; GRAMMENOS, Wassilios; CRAIG, Ian, Robert; BOUDET, Nadege; MUeLLER, Bernd; DIETZ, Jochen; LAUTERWASSER, Erica, May, Wilson; LOHMANN, Jan, Klaas; MONTAG, Jurith; WO2013/113720; (2013); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Adding a certain compound to certain chemical reactions, such as: 156-81-0, Pyrimidine-2,4-diamine, 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, COA of Formula: C4H6N4, blongs to pyrimidines compound. COA of Formula: C4H6N4

General procedure: Vilsmeier reagent was prepared by mixing ice-cold dry DMF (50 ml) and POCl3 (30.0 mmol, 2.8 ml). The mixture was stirred for 15 min at 25 C. To the previous mixture, aminopyrimidines (10.0 mmol) in dry DMF (5.0 ml) were added over a period of 15 min at 0-5 C. The reaction mixturewas stirred for 24 h at 25 C.The mixture was then added to cold, saturated aq. K2CO3 andextracted with diethyl ether. The organic layer was washed withwater, dried over anhydrous Na2SO4, and evaporated underreduced pressure to afford the crude product, whichwas purified ina silica gel column chromatography using hexane/ethyl acetate(9:1) as an eluent to give the title compounds 2 and 8. 4.3.1. 2,4-Diaminopyrimidine-5-carbaldehyde (2) Brown powder, yield 59%; 1H-NMR [DMSO-d6, 400 MHz]: (delta,ppm) 7.10 (d, 2H, NH2, exchange with D2O), 7.52 (d, 2H, NH2, exchangewith D2O), 8.32 (s, 1H, H6-pyrimidine), 9.45 (CHO); 13C NMR[DMSO-d6, 100 MHz]: (delta, ppm) 106.2 (C5-pyrimidine), 162.7(C4-pyrimidine), 164.4 (C6-pyrimidine), 167.0 (C2-pyrimidine),189.5 (CHO).

The synthetic route of 156-81-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; AlNeyadi, Shaikha S.; Salem, Alaa A.; Ghattas, Mohammad A.; Atatreh, Noor; Abdou, Ibrahim M.; European Journal of Medicinal Chemistry; vol. 136; (2017); p. 270 – 282;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 302964-08-5, 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. 302964-08-5, name is 2-((6-Chloro-2-methylpyrimidin-4-yl)amino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide. A new synthetic method of this compound is introduced below.

Compound 13 can then be obtained by treaUng compound 12 w[th TFA. Subsequent coupIng of compound 13 with compound 8 n the presence of DIPEA can afford compound 14.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,302964-08-5, 2-((6-Chloro-2-methylpyrimidin-4-yl)amino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide, and friends who are interested can also refer to it.

Reference:
Patent; COMBS, Colin; MULLER, Gerhard; DAMEN, Eddy; NAGAMOTO-COMBS, Kumi; (73 pag.)WO2017/100703; (2017); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of 33097-13-1, 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. 33097-13-1, name is 4,6-Dichloro-2-(methylthio)pyrimidine-5-carbonitrile. A new synthetic method of this compound is introduced below.

[0329] Step 1 : To a suspension of 4,6-dichloro-2-(methylthio)pyrimidine-5-carbonitrile (330 mg, 1.5 mmol) in DMF (3 mL) was added m-anisidine (231 mg, 1.875 mmol). After stirring at room temperature for 4 h, the mixture was diluted with water, the resulting precipitate was collected by filtration to give 4-chloro-2-(methythio)-6-(3- (methoxy)phenylamino)pyrimidin-5-carbonitrile (600 mg).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,33097-13-1, its application will become more common.

Reference:
Patent; PORTOLA PHARMACEUTICALS, INC.; PANDEY, Anjali; XU, Qing; HUANG, Wolin; JIA, Zhaozhong J.; SONG, Yonghong; WO2012/61415; (2012); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia