Day: September 1, 2021

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. 69034-12-4, name is 2-Chloro-5-(trifluoromethyl)pyrimidine. A new synthetic method of this compound is introduced below., Recommanded Product: 2-Chloro-5-(trifluoromethyl)pyrimidine

STEP 2A: 2-[(3R)-3-METHYLPIPERAZIN-1-YL]-5-(TRIFLUOROMETHYL)PYRIMIDINE (0208) To a solution of tert-butyl (2R)-2-methylpiperazine-l-carboxylate (2.2 g, 11.0 mmol, 1.0 eq) and 2-chloro-5-(trifluoromethyl)pyrimidine (2.0 g, 11.0 mmol, 1.0 eq) in 1 -methyl-2-pyrrolidone (NuMuRho,IotaOmicron mL) was added N^V-diisopropylethylamine (5.7 mL, 44.0 mmol, 4.0 eq) and the reaction mixture heated to 100 C for 1 hr. The reaction mixture was cooled, diluted heavily with EtOAc, and washed repeatedly with brine (5x). The organic layer was dried over Na2SC>4 and concentrated. Silica gel column (80 g) was loaded using methylene chloride and run using an increasing gradient of EtOAc (5-90%) in hexanes over 20 min. The chromatographed material was dissolved in dioxane (25 mL) and treated with a solution of 4M HC1 in dioxane (6 mL). The resulting thick white suspension was concentrated, dissolved in MeOH, and made basic with the addition of MP-carbonate. Following removal of the resin and concentration of the filtrate, the free base of 2-[(3R)-3-methylpiperazin-l-yl]-5- (trifluoromethyl)pyrimidine 2a (1.9 g, 7.6 mmol, 69% over two steps) was isolated as a white solid.

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, 69034-12-4, 2-Chloro-5-(trifluoromethyl)pyrimidine.

Reference:
Patent; NEUROCRINE BIOSCIENCES, INC.; HARRIOTT, Nicole; PAGANO, Nicholas; (135 pag.)WO2017/79641; (2017); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 1753-50-0, 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. 1753-50-0, name is 2-Chloropyrimidine-5-carbonitrile. A new synthetic method of this compound is introduced below.

To a mixture of (S)-2-amino-4-(cyclopropyl(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) butyl)amino) butanoic acid trifluoroacetate (100 mg, 217 mumol) in 4:1 THF/H2O (2 mL) was added 2-chloropyrimidine-5-carbonitrile (33 mg, 239 mumol) and NaHCO3 (55 mg, 651 mumol) and the resulting mixture was stirred at 70 C. for 1 h and then allowed to cool to rt and then concentrated in vacuo. The crude residue was purified by reverse phase prep-HPLC to give the title compound. LCMS (ESI+): m/z=450.2 (M+H). H NMR (400 MHz, Methanol-d4): delta ppm 8.58 (br s, 1H) 8.47 (br s, 1H) 7.36 (d, J=7.34 Hz, 1H) 6.50 (d, J=7.34 Hz, 1H) 4.42 (t, J=6.05 Hz, 1H) 3.35-3.45 (m, 2H) 2.93-3.12 (m, 2H) 2.80-2.92 (m, 2H) 2.74 (t, J=6.24 Hz, 2H) 2.64 (br dd, J=7.83, 5.75 Hz, 2H) 2.21-2.32 (m, 1H) 2.00-2.18 (m, 2H) 1.84-1.93 (m, 2H) 1.66-1.82 (m, 4H) 0.56-0.70 (m, 4H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,1753-50-0, 2-Chloropyrimidine-5-carbonitrile, and friends who are interested can also refer to it.

Reference:
Patent; Pliant Therapeutics, Inc.; CHA, Jacob; DONG, Chengguo; HOM, Timothy; JIANG, Lan; LEFTHERIS, Katerina; LI, Hui; MORGANS, JR., David J.; MUNOZ, Manuel; REILLY, Maureen; ZHENG, Yajun; (232 pag.)US2019/276449; (2019); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

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 1753-48-6, name is 2-Aminopyrimidine-5-carbonitrile. This compound has unique chemical properties. The synthetic route is as follows. Safety of 2-Aminopyrimidine-5-carbonitrile

A mixture of 368 mg (1 equiv) of tert-butyl 2-(5-bromo-3-carbamoyl-1H-indazol- 1-yl) acetate (112), 2-aminopyrimidine-5-carbonitrile (120 mg, 1 equiv), and cesium carbonate (650 mg, 2 equiv) in DMF (20 mL) was purged with argon in a pressure vessel for 5 min, then tris(dibenzylideneacetone) dipalladium(O) (0.01 equiv) and 4,5-bis(diphenylphosphino)-9,9- dimethylxanthene (0.01 equiv) were added under argon. The pressure vessel was sealed and heated at 100 C for 24 h. The reaction mixture was then cooled to rt and the solvent was removed under reduced pressure. The remaining residue was purified by flash column chromatography (eluted with DCM/CH3OH) to give tert-butyl 2-(3-carbamoyl-5-((5-cyanopyrimidin-2-yl)amino)-1H-indazol-1-yl)acetate (117).

With the rapid development of chemical substances, we look forward to future research findings about 1753-48-6.

Reference:
Patent; ACHILLION PHARMACEUTICALS, INC.; WILES, Jason, Allan; PHADKE, Avinash, S.; DESHPANDE, Milind; AGARWAL, Atul; CHEN, Dawei; GADHACHANDA, Venkat, Rao; HASHIMOTO, Akihiro; PAIS, Godwin; WANG, Qiuping; WANG, Xiangzhu; (319 pag.)WO2017/35351; (2017); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

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. 5018-38-2, name is 4,6-Dichloro-5-methoxypyrimidine. This compound has unique chemical properties. The synthetic route is as follows. Recommanded Product: 5018-38-2

1-(5-Methoxy-4-pyrimidinyl)piperazine Piperazine (20 g) was dissolved in water (100 mL) in a Parr bottle and then solid 4,6-dichloro-5-methoxypyrimidine (5.00 g, 27.9 mmole) was added. The mixture was vigorously stirred for 2 h at room temperature during which the 4,6-dichloro-5-methoxypyrimidine dissolved. The stirring bar was removed, catalyst (10% Pd/C, 1.0 g) was added to the turbid solution, and the mixture was then hydrogenated (60 psi, 3 h) at room temperature. The catalyst was filtered off and the filtrate extracted 3 times with CH2 Cl2. The CH2 Cl2 extracts were dried over Na2 SO4 and concentrated in vacuo to give a clear oil which solidified upon standing (3.34 g, 61.7%). This crude product was Kugelrohr distilled (yield 3.24 g), dissolved in acetonitrile, and concentrated HCl was added to precipitate the product as a white powder which was dried in vacuo (4.32 g, 94.0% from crude product, m.p. 219-221.5 C.).

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

Reference:
Patent; Bristol-Myers Squibb Company; US5300506; (1994); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Electric Literature of 1231930-42-9, 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. 1231930-42-9, name is 6-(2-Chloro-5-fluoropyrimidin-4-yl)-4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazole, molecular formula is C15H13ClF2N4, 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.

Under nitrogen, 118 mg of N1-(2-dimethylaminoethyl)-5-methoxy-N1-methyl-2-nitro-1,4-phenylenediamine,140 mg of 6-(2-chloro-5-fluoropyrimidin-4-yl)-4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazole,282 mg of Cs2CO3, 120 mg of Pd2(dba)3 and 108 mg of BINAP were dissolved in 20 ml of 1,4-dioxane, and the mixture was heated at 140 C for 3 h.The insoluble matter in the reaction liquid was cooled and filtered, and the filter cake was washed with dichloromethane, and the filtrate was evaporated to dryness under reduced pressure.Obtaining N1-(2-dimethylaminoethyl)-N4-(5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazole-6-yl) Pyrimidine-2-yl)-5-methoxy-N1-methyl-2-nitro-1,4-phenylenediamine 80 mg as a reddish brown solid.

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 1231930-42-9, 6-(2-Chloro-5-fluoropyrimidin-4-yl)-4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazole.

Reference:
Patent; WISDRUG INNOCATION PHARMACY RES BEIJING CO LTD; Wentao Chuangxin Pharmaceutical (Beijing) Co., Ltd.; ZHU XIZHEN; Zhu Xizhen; DENG CHENGJUN; Deng Chengjun; ZHOU ZHONGXIANG; Zhou Zhongxiang; (17 pag.)CN107827875; (2018); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Electric Literature of 131860-97-4, 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. 131860-97-4, name is (E)-Methyl 2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)-3-methoxyacrylate. A new synthetic method of this compound is introduced below.

Embodiment 20 (0104) This embodiment is provided to describe the method for preparing the azoxystrobin compound represented by formula (4) in a one-pot approach in the present invention. (0105) Under nitrogen protection, add 0.1 mol 4,6-dichloropyrimidine, 0.015 mol anhydrous potassium carbonate, 0.15 mol methyl formate, and 0.002 mol 2-methyl-1,4-diazabicyclo[2.2.2]-octane into 100 mL dimethyl benzene solution of 0.1 mol 3-(alpha-methoxy)methylene benzofuran-2-(3H)-ketone sequentially, start stirring, cool down to 5 C., and then control the temperature at 5-20 C., add 5 mL 29 wt. % methanol solution of sodium methoxide in droplets within 60 min., and then let the reaction proceed for 30 min. while stirring, to obtain a solid-containing mixture. Measured by GC, the content of the mixture of methyl 2-(2-((6-chloropyridinyl-4-)oxy)phenyl)-3,3-dimethoxyacrylate and methyl (E)-2-{2-[6-chloropyrimidinyl-4-oxy]phenyl}-3-methoxyacrylate is 92%; measured by LC, the ratio of methyl 2-(2-((6-chloropyridinyl-4-)oxy)phenyl)-3,3-dimethoxyacrylate to methyl (E)-2-{2-[6-chloropyrimidinyl-4-oxy]phenyl}-3-methoxyacrylate is 76:24. Next, distill out methyl formate and methanol under negative pressure; after the end of desolventizing under negative pressure, add 50 g water into the reaction bulb, stir so that the solid is dissolved, keep the solution still for stratification, and then condense the organic phase, to obtain viscous liquid. Add 0.003 mol dimethyl sulfate and 0.1 mol acetic anhydride into the obtained viscous liquid, heat up to 105 C., keep at the temperature and reflux, and let the reaction proceed for 60 min. Measured by GC, the content of the mixture of methyl 2-(2-((6-chloropyridinyl-4-)oxy)phenyl)-3,3-dimethoxyacrylate and methyl (E)-2-{2-[6-chloropyrimidinyl-4-oxy]phenyl}-3-methoxyacrylate is 91%; measured by LC, the ratio of methyl 2-(2-((6-chloropyridinyl-4-)oxy)phenyl)-3,3-dimethoxyacrylate to methyl (E)-2-{2-[6-chloropyrimidinyl-4-oxy]phenyl}-3-methoxyacrylate is 1.0:99; condense the reaction liquid under negative pressure to remove the solvent, to obtain viscous liquid compound methyl (E)-2-{2-[6-chloropyrimidinyl-4-oxy]phenyl}-3-methoxyacrylate. (0106) Add 80 ml butyl acetate, 0.085 mol 2-cyanophenol, 0.095 mol anhydrous potassium carbonate, and 0.003 mol 2,6-dimethyl-1,4-diazabicyclo[2.2.2]-octane into the obtained viscous liquid above, heat up the reaction mixture to 100 C. while stirring, keep at the temperature and let the reaction proceed for 250 min., and monitor the reaction situation with a gas chromatograph (GC). When the GC indicates that the normalized area of methyl (E)-2-[2-(6-chloropyrimidinyl-4-oxy)phenyl]-3-methoxyacrylate is smaller than 1%, add 50 ml water into the reaction system, stir for 10 min., keep the solution still for 10 min. at 80 C. for stratification, and then remove the aqueous phase, and repeat washing the organic phase once by adding water again; cool down the obtained organic phase to -5 C., so that crystals precipitate; then, filter to obtain a wet filer cake of azoxystrobin, rinse the filter cake with butyl acetate, and heat up the rinsed filter cake to approx. 50-60 C. with 50 ml methanol, beat and wash; then, filter and dry; thus, 28.1 g (0.0697 mol) light yellow solid is obtained, the purity is 99.6%, and the yield ratio is 69.7%.

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; NUTRICHEM COMPANY LIMITED; SHANGYU NUTRICHEM CO., LTD.; CHEN, Jianwei; WANG, Wenjun; CHI, Jianhong; ZHAO, Yongchang; DENG, Xufang; WANG, Long; JIN, Wentao; CHEN, Guobin; (15 pag.)US2016/200687; (2016); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 16019-31-1 ,Some common heterocyclic compound, 16019-31-1, molecular formula is C7H6Cl2N2, 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: Ingenol-5,20-acetonide (0.13 mmol) dissolved in DMF (0.3 ml) was added a heteroaryl halide (0.65 mmol) and caesium carbonate (0.26 mmol). The mixture was stirred at 60 C. for 1 hour. After cooling to r.t. the mixture was partitioned between diethylether (2 ml) and saturated aq. sodium hydrogencarbonate (0.5 ml). The ether phase was isolated, dried over sodium sulphate and concentrated in vacuo. The residue was purified by flash chromatography (heptane?heptane/ethyl acetate 7:3), giving the title compound as a white solid. Compound 204 was prepared according to Procedure a. Starting material: 5-Allyl-4,6-dichloro-pyrimidine. 1H NMR (300 MHz, CDC13) oe 8.38 (s, 1H), 6.14-6.13 (m, 1H), 6.03 (s, 1H), 5.92-5.77 (m, 2H), 5.10-5.02 (m,2H), 4.27-4.10 (m, 3H), 4.06 (t, 1H), 3.56 (s, 1H), 3.46 (dt,2H), 2.67-2.61 (m, 1H), 2.28-2.19 (m, 1H), 1.80 (d, 3H),1.79-1.70 (m, 1H), 1.47 (s, 3H), 1.45 (s, 3H), 1.07 (s, 3H),1.05 (s, 3H), 1.02 (d, 3H), 0.94-0.86 (m, 1H), 0.74-0.66 (m,1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,16019-31-1, its application will become more common.

Reference:
Patent; LEO LABORATORIES LIMITED; Liang, Xifu; Hoegberg, Thomas; N°rremark, Bjarne; Mansson, Kristoffer; Ryttersgaard, Carsten; Grue-S°rensen, Gunnar; US2015/175622; (2015); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 13036-50-5 ,Some common heterocyclic compound, 13036-50-5, molecular formula is C10H7ClN2, 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 2,4-dichloropyrimidine (149 mg, 1 mmol) in THF (5 mL), tetrakis (triphenylphosphine) palladium (23 mg, 2 mol%) and 0.5M solution of phenylzinc bromide (2.1 mL, 1.05 mmol) in THF were added. The reaction mixture was stirred at50 C for overnight. Then it was added saturated ammonium chloride solution and extracted with EtOAc twice. The organic layers were combined, washed with water and dried(MgS04). Evaporation of solvent gave a yellow residue which was purified by Prep. HPLC to afford a yellowish oil as 2-chloro-4-phenyl- pyrimidine to carry on. To a solution of intermediate 2 (20 mg, 0.039 mmol) in DMF (3 mL), NaH (3.9 mg of 60% dispersion in mineral oil, 0.0975 mmol) was added at0 C. The reaction mixture was then warmed to rt. and stirred for 1 hr. Then 2-chloro-4-phenyl- pyrimidine prepared above (18 mg as crude) was added. The reaction mixture was stirred at rt. for overnight. It was then quenched with water and extracted with EtOAc. The organic layer was separated, washed with brine and dried(MgS04). Evaporation of solvent gave yellowish oil which was then purified by Prep. HPLC to give a thick colorless oil as final product (Compound 335) as TFA salt. (5.5 mg, 18% yield) ‘H NMR (CD30D, 300 MHz) 0.92-1. 12 (m, 11 H). 1.25 (m, 2 H), 1.44 (dd, J=9. 2, 5.5 Hz,1 H), 1.89 (dd, J=8. 1,5. 5 Hz, 1H), 2.17-2. 37 (m, 2 H), 2.57 (m, 1 H), 2.95 (m,1 H), 3.52 (s, 3 H), 4.14 (m,1 H), 4.24-4. 38 (m, 2 H), 4.51 (m,1 H), 5.13 (d, J=10. 2 Hz,1 H), 5.31 (d, J=17. 2 Hz,1 H), 5.77 (m,1 H), 5.86 (s,1 H), 7.48-7. 60 (m,3 H), 7.66 (d, J=5.3 Hz, 1 H), 8.18 (m,2 H), 8.60 (d, J=5.1 Hz, 1 H). LC-MS (retention time: 1.947 min. ), MS m/z 669(MH+).

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. 13036-50-5, 2-Chloro-4-phenylpyrimidine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; WO2003/99274; (2003); A1;,
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. 428854-24-4, name is 2-(1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidine-4,5,6-triamine, molecular formula is C17H15FN8, 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. Recommanded Product: 2-(1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidine-4,5,6-triamine

Acetone (SO ml) was added to 2-(l-(2-fluorobenzyl)-1H-pyrazo]o[3,4-b]pyridin-3-yl) pyrimidine-4,S,6-triamine (10 gms) compound of formula-2 at 25-30C and stirred for 10 minutes at the same temperature. Dimethyl sulfate (10.79 gms) was slowly added to the reaction mixture at 25-30C and stirred for 40 hours at the same temperature. Filtered the precipitated solid, washed with acetone and dried to get the title compound. Yield: 8 gms.

With the rapid development of chemical substances, we look forward to future research findings about 428854-24-4.

Reference:
Patent; MSN LABORATORIES PRIVATE LIMITED, R&D CENTER; THIRUMALAI RAJAN, Srinivasan; ESWARAIAH, Sajja; VENKATA PANAKALA RAO, Gogulapati; RAJESHWAR REDDY, Sagyam; BALA NARSAIAH, Eppaturi; SRINIVASULU, Rangineni; (32 pag.)WO2018/96550; (2018); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Adding a certain compound to certain chemical reactions, such as: 1920-66-7, 4-Amino-2-chloro-5-nitropyrimidine, 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, HPLC of Formula: C4H3ClN4O2, blongs to pyrimidines compound. HPLC of Formula: C4H3ClN4O2

General procedure: Commercial 1a (50mmol) was dissolved in dichloromethane (80mL), mixture was cooled to 0C, solution of NH3 in MeOH (4mol/L, 12.5mL) was added by dripping slowly, after 30min, the mixture maintained at 0C for 1h. The reaction mixture was filtered, and the insoluble material was washed with ethyl acetate (20mL) and water (30mL) to get 2a (8.66g), yield 90%. Compound 2a (50mmol) was dissolved in THF (40mL), then absolute ethyl alcohol (20mL), water (20mL), Fe (4eq) and ammonium chloride (2eq) were added. The mixture was refluxed until raw material disappeared. The reaction mixture was filtered and filter liquor was evaporated by reducing pressure to get 3a (2.4g), yield 33%. Compound 3a (17mmol) was dissolved in DMF (30mL), triethylamine (3eq) was added, and acetyl isothiocyanate (1eq) was added by dripping slowly, the mixture was stirred at room temperature for 30min, then 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 1.5eq) was added and stirred overnight at room temperature. Pulled the mixture into ice water, using concentrated HCl regulates pH to 1, the mixture was filtered, the residue was dried and washed by water to give 4a (2.0g), yield 60%. Compound 4a (10mmol), 5a/5b/5c/5d/5e (1.2eq), 120mL 1,4-dioxane, 10mL water, Pd(dppf)Cl2 (0.1eq), and NaHCO3 (1eq) were added to a round-bottomed flask, mixture was stirred for 12h at 90C. Solvent was removed by reduced pressure distillation, residue was purified by preparative HPLC (MeCN+0.05% TFA, H2O 0.1%+TFA), Ta-e were finally obtained from above steps, yield 0.58-5.5%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,1920-66-7, 4-Amino-2-chloro-5-nitropyrimidine, and friends who are interested can also refer to it.

Reference:
Article; Guo, Hui; Jin, Ru-Yi; Li, Zhi; Long, Xu; Tang, Tian; Tang, Yu-Ping; Xie, Hong-Lei; Yan, Hao; Zhou, Jing; Zhou, Sha; Zuo, Zheng-Yu; Bioorganic Chemistry; vol. 98; (2020);,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia