Month: November 2020

Some common heterocyclic compound, 2849-93-6, name is 1H-Benzimidazole-2-carboxylic acid, molecular formula is C8H6N2O2, 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. 2849-93-6

A mixture of 3-nitro-N-(piperidin-4-yl)pyridin-2-amine hydrochloride (intermediate 58, 580 mg, 2.3 mmol), 1H-benzo[d]imidazole-2-carboxylic acid (365 mg, 2.3 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (365 mg, 2.7 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (516 mg, 2.7 mmol) and N-methylmorpholine (455 mg, 4.6 mmol) in dry dimethylformamide (15 mL) was stirred at room temperature overnight. The mixture was diluted with water (60 mL), and extracted with ethyl acetate (2*50 mL). The organic layer was washed with brine, dried over sodium sulfate and concentrated to give the crude compound which was purified by silica chromatography to afford (1H-benzo[d]imidazol-2-yl)(4-((3-nitro-pyridin-2-yl)amino)piperidin-1-yl)methanone (600 mg, 1.64 mmol, 72.8% yield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2849-93-6, its application will become more common.

Reference:
Patent; AMGEN INC.; Allen, Jennifer R.; Amegadzie, Albert; Andrews, Kristin L.; Brown, James; Chen, Jian J.; Chen, Ning; Harrington, Essa Hu; Liu, Qingyian; Nguyen, Thomas T.; Pickrell, Alexander J.; Qian, Wenyuan; Rumfelt, Shannon; Rzasa, Robert M.; Yuan, Chester Chenguang; Zhong, Wenge; US2013/225552; (2013); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

288-32-4,Some common heterocyclic compound, 288-32-4, name is 1H-Imidazole, molecular formula is C3H4N2, 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: A dry flask was charged with the nitrogen containing heterocycles (1.5 mmol), aryl halides (1 mmol), potassium carbonate(2 mmol) and CuMeSal (0.01 mmol) then anhydrous DMSO (5 ml) was added. The reaction mixture was stirred at 110C, open to air, for 3h , cooled to room temperature, filtered, and the precipitate was washed with DMSO (2 ml) then stirred with ice water (30 ml) and extracted with ethyl acetate (3 ¡Á 50 ml),dried over sodium sulfate and the solvent was removed under reduced pressure.The residue was purified by chromatography or recrystallization as indicated with each compound.

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

Reference:
Article; Farahat, Abdelbasset A.; Boykin, David W.; Tetrahedron Letters; vol. 55; 19; (2014); p. 3049 – 3051;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

1080-79-1, These common heterocyclic compound, 1080-79-1, name is Diethyl 1H-imidazole-4,5-dicarboxylate, 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. N-o-Nitrophenylimidazole 4,5-dicarboxylic acid diethyl ester To a solution of o-fluoronitrobenzene (106 g) and imidazole 4,5-dicarboxylic acid diethyl ester (106 g) in one liter of N,N-dimethyl formamide (DMF) was added anhydrous potassium carbonate (200 g). The reaction mixture was stirred vigorously for at least four hours. After removal of solvent under oil pump vacuum, the residue was treated with water, then extracted with chloroform (300 ml*3). The combined chloroform extracts were washed with water, dried by magnesium sulfate, then concentrated under vacuum to an oil. Upon treatment with ether, the oil was solidified and the product was obtained as a white solid (136 g, 81% yield). Recrystallized from chloroform-hexane, m.p. 93-95 C.

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 1080-79-1.

Reference:
Patent; USV Pharmaceutical Corporation; US4440929; (1984); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

A common compound: 15788-16-6, name is 1H-Benzo[d]imidazole-5-carboxylic acid, belongs to imidazoles-derivatives compound, 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. 15788-16-6

8.1. PREPARATION OF 5-BENZIMIDAZOLE-CARBOXYLIC ACID, METHYL ESTER A 500 ml round bottom flask equipped with a heating mantle, reflux condenser, and a DrieriteR filled drying tube was charged with 16.22 g (0.10 mol) of 5-benzimidazolecarboxylic acid (Aldrich), 400 ml of anhydrous methanol and then (Caution)) 20 ml of concentrated sulfuric acid (Fisher). The reaction mixture was heated to reflux for 18 h and then cooled to ambient temperature. Approximately 75% of the solvents were removed under vacuum and then the remaining liquid residue was slowly poured into 500 ml of saturated sodium bicarbonate solution. The resultant two phase system was then extracted with three 250 ml portions of ethyl acetate. The organic layers were combined and washed with three 250 ml portions of 5% sodium bicarbonate solution followed by one 250 ml portion of brine. The ethyl acetate layer was dried over MgSO4, filtered and the solvents were then removed under reduced pressure to give 15.68 g (0,089 mol, 89% yield) of 5-benzimidazolecarboxylic acid, methyl ester, as a tan solid. 1 H NMR (CDCl3) delta7.3-7.9 (m, 3H), 3.70 (s, 3H).

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, 15788-16-6, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Cytogen Corporation; US5326856; (1994); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

17334-08-6, These common heterocyclic compound, 17334-08-6, name is (1-Methyl-1H-imidazol-2-yl)methanol, 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 2-hydroxymethyl-1-methylimidazole (874 mg) was added thionyl chloride (10 ml) at 0C, and the mixture was heated for 30 minutes under nitrogen atmosphere at 90C. The mixture was allowed to be at room temperature. The solvent was distilled off under reduced pressure and the obtained residue was recrystallized from ethyl acetate, to give 2-chloromethyl-1-methylimidazole hydrochloride (1.15 g) as brown crystals. 1H-NMR (200 MHz, DMSO-d6) delta 3.88 (3H, s), 5.19 (2H, s), 7.72 (1H, d, J = 1.8 Hz), 7.78 (1H, d, J = 1.8 Hz). Elemental Analysis C5H8N2Cl2 Calcd. C, 35.95; H, 4.83; N, 16.77; Found. C, 35.74; H, 5.03; N, 16.45.

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 17334-08-6.

Reference:
Patent; Takeda Chemical Industries, Ltd.; EP1422228; (2004); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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 2849-93-6 as follows. 2849-93-6

General procedure: A reaction mixture of H2BIC (0.0162 g,0.1mmol), Gd(NO3)3¡¤6H2O (0.0451 g, 0.1 mmol), Na2C2O4 (0.0134 g, 0.1 mmol), CH3CN(5 mL) and EtOH (5 mL) was stirred for 20 min, then transferred and sealed in a 20mLTeflon-lined autoclave. The system was heated in an oven at 393K for 72 h and cooled toroom temperature at 5Kh1. The resulting colorless flaky crystals were collected, washedwith ethanol and dried in air. Yield: ca. 71% (based on Gd). Anal. Calcd forC24H15N6O6Gd (%): C, 44.99; H, 2.36; N, 13.12. Found (%): C, 45.21; H, 2.88; N, 12.92.IR (KBr)/cm1: 3131(br, m), 1659(s), 1616(s), 1528(m), 1498(m), 1460(s), 1394(s),1319(s), 1307(m), 1230(w), 1029(w), 989(w), 850(m), 821(m), 773(w), 741(s), 657(m),592(m).

According to the analysis of related databases, 2849-93-6, the application of this compound in the production field has become more and more popular.

Reference:
Article; Qiao, Chengfang; Xia, Zhengqiang; Wei, Qing; Zhou, Chunsheng; Zhang, Guochun; Chen, Sanping; Gao, Shengli; Journal of Coordination Chemistry; vol. 66; 7; (2013); p. 1202 – 1210;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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. 46006-36-4, name is 1H-Benzimidazole-7-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., 46006-36-4

A mixture of l-(3-((5-aminopyridin-3-yl)amino)-5-methyl-5H-chromeno[4,3- c]pyridin-8-yl)pyrrolidin-2-one (60 mg, 0.14 mmol, HC1 salt), lH-benzo[d]imidazole-4- carboxylic acid (57 mg, 0.35 mmol) and EDCI.HC1 (30 mg, 0.16 mmol) in pyridine (2 mL) was heated at 30 C for 12 h. A yellow suspension was formed. LCMS (Rt = 0.586 min; MS Calcd: 531.2; MS Found: 532.2 [M+H]+). The mixture was concentrated and the residue was poured into water (20 mL) and stirred for 2 minutes. The aqueous layer was extracted with ethyl acetate (20 mL x3). The combined organic layer was washed with water (20 mL x2) and brine (20 mL), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by prep-HPLC (0.225% FA as an additive) and lyophilized to give N-(5-((5-methyl- 8-(2-oxopyrrolidin-l-yl)-5H-chromeno[4,3-c]pyridin-3-yl)amino)pyridin-3-yl)-lH- benzo[d]imidazole-4-carboxamide (41.7 mg, yield: 55%) as a yellow solid. (1559) NMR (400 MHz DMSO-rie) d 1.56 (3H, d, J= 6.5 Hz), 2.01-2.10 (2H, m), 2.52-2.54 (2H, m, overlapped with the peak of DMSO), 3.84 (2H, t, J= 7.9 Hz), 5.30 (1H, q , J= 6.7 Hz), 6.79 (1H, s), 7.32 (1H, dd, J= 8.7, 2.1 Hz), 7.40 (1H, d, J= 2.3 Hz), 7.47 (1H, t , J= 7.8 Hz), 7.88-7.92 (2H, m), 8.03 (1H, d, J= 7.5 Hz), 8.62 (1H, d, J= 2.0 Hz), 8.66 (1H, s), 8.72 (1H, s), 8.75 (1H, t, J= 2.0 Hz), 8.81 (1H, d, J= 2.0 Hz), 9.72 (1H, brs), 12.06 (1H, brs).

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.

Reference:
Patent; PETRA PHARMA CORPORATION; KESICKI, Edward A.; LINDSTROeM, Johan; PERSSON, Lars Boukharta; VIKLUND, Jenny; FORSBLOM, Rickard; GINMAN, Tobias; HICKEY, Eugene R.; DAHLGREN, Markus K.; GERASYUTO, Aleksey I.; (391 pag.)WO2019/126730; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

113775-47-6, A common compound: 113775-47-6, name is Dexmedetomidine, belongs to imidazoles-derivatives compound, 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 mixture of (+)-(S)-4-[1-(2,3-dimethyl-phenyl)-ethyl]-1H-imidazole (dexmeditomidine; 2.00 g, 10.0 mmol) prepared as described in Cordi et al., Synth. Comm. 26: 1585 (1996), in THF (45 mL) and water (40 mL) was treated with NaHCO3 (8.4 g, 100 mmol) and phenylchlorothionoformate (3.7 mL, 27.4 mmol). After stirring for four hours at room temperature, the mixture was diluted with water (30 mL) and ether (75 mL). The organic layer was removed, and the aqueous layer extracted with ether (2¡Á50 mL). The organic layers were dried over MgSO4 and filtered. The residue was concentrated under vacuum, diluted with MeOH (54 mL) and reacted with NEt3 (6.5 mL) at room temperature for 16 hours. The solvent was removed under vacuum and replaced with 30% CH2Cl2:hexane. The solvent was removed again and solids formed. After further resuspension in 30% CH2Cl2:hexane, the solid was collected on a filter, washed with CH2Cl2:hexane and dried under vacuum to give Compound 1 ((+)-(S)-4-[1-(2,3-dimethyl-phenyl) ethyl]-1,3-dihydro-imidazole-2-thione) 1.23 g (53%). Characterization of the product yielded the following. Optical rotation: [a]D20+14 (c 1.25 in MeOH). 1H NMR: (300 MHz, DMSO) d 11.8 (s, 1H), 11.6 (s, 1H), 7.03-7.01 (m, 2H), 6.95-6.91 (m, 1H), 6.50 (s, 1H), 4.15 (q, J=6.9 Hz, 1H), 2.25 (s, 3H), 2.20 (s, 3H), 1.38 (d, J=6.9 Hz, 3H)

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, Dexmedetomidine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Allergan, Inc.; US2005/59664; (2005); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

A common heterocyclic compound, 71759-89-2, name is 5-Iodo-1H-imidazole, molecular formula is C3H3IN2, 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. 71759-89-2.

Step 1 Following a procedure similar to that outlined in Chem. Comm. 2004, 188-189: A solution of 2,5-difluorophenylboronic acid (47 mg, 0.30 mmol), 4-iodo-1H-imidazole (46 mg, 0.24 mmol), copper(I) chloride (1.8 mg, 0.018 mmol), and 1 mL of methanol was stirred under air at 60 C. for 3 h, then concentrated. Column chromatography (0-33% EtOAc/hexanes) afforded 14.5 mg (20%) of 1-(2,5-difluorophenyl)-4-iodo-1H-imidazole as a white solid.

The synthetic route of 5-Iodo-1H-imidazole has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hendricks, Robert Than; Hermann, Johannes; Kondru, Rama; Lou, Yan; Lynch, Stephen M.; Owens, Timothy D.; Soth, Michael; US2011/230462; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

144689-93-0, The chemical industry reduces the impact on the environment during synthesis 144689-93-0, name is Ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate, I believe this compound will play a more active role in future production and life.

400 ml of acetone was added to a 1 L glass reaction flask, and 111. 4 g of N-(triphenylmethyl)-5-(4′-bromomethylbiphenyl-2-yl)tetrazole, 48.0 of ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1H-imidazol-5-carboxylate was added with stirring, 55.2 g of potassium carbonate, 6.4 g of tetrabutylammonium bromide, heated to 50-60 C, After the incubation reaction for 20 hours, the temperature was lowered to 20-30 C, 200 ml of water was added, stirred for 30 minutes, and filtered, and the filter cake was successively rinsed with 200 ml of water and 200 ml of acetone. The filter cake was air-dried at 40-50 C for 12 hours to give a white solid, 130.0 g ( Intermediate 1), yield: 90.7%, HPLC: 98.6%.

The chemical industry reduces the impact on the environment during synthesis Ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Jiashi (Hunan) Pharmaceutical Technology Co., Ltd.; Dai Yongzhi; Liu Hu; Zhu Laifa; Cai Jian; (8 pag.)CN108341804; (2018); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem