Month: April 2021

Electric Literature of 20485-43-2,Some common heterocyclic compound, 20485-43-2, name is 1-Methyl-1H-imidazole-2-carboxylic acid, molecular formula is C5H6N2O2, 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)Resin swelling: 400 mg of Fmoc-protected phenylhydrazine (0.66 mmol / g, 0.264 mmol) and 3 mL of CH2CI2 were added to a 10 mL solid phase reactor, the resin was swollen for 30 min, CH2CI2 was withdrawn, (b)Remove Fmoc protecting group: A solution of 3 mL of 20% piperidine / DMF was added to the swollen resin in step (a), N2 After bubbling, lOmin, the solvent was extracted, then 3 mL of 20% piperidine / DMF solution was added, N2 was bubbled and mixed. After lOmin, the resin was washed with DMF (4 x 3 mL) and the resin was washed with 3 mL of anhydrous DMF ,spare; (c) Amino acid condensation: A solution of 4-tert-butoxycarbonylamino-1-methyl-1H-pyrrole-2-carboxylic acid (254 mg, 1.056 mmol) and triphosgene (BTC, 128 mg, 0.433 mmol) in 2 mL of anhydrous THF was added to the solution Slowly dropwise trimethyl P-pyridine (Col 1 idine, 488yL, 3.696mmol), the reaction immediately produced a large number of white precipitate, added reaction 3min, (5%, nu / nu), the white precipitate was completely disappeared, and the reaction solution was transferred to the phenylhydrazine resin in which the protecting group was removed in step (b), N2 was bubbled and mixed, and the condensation reaction was 0.5 ~ Lh, the reaction solution was extracted, and the resin was washed with DMF (4 x 3 mL),(d)Removal of tert-butoxycarbonyl protecting group: Washed with CH2C12 (2 X 3 mL) Extraction of CH2C12, adding 3. OmLTFA / benzoic acid / Eta2Omicron (nu: nu: nu = 92: 5: 2.5) mixed solution removal step (b) The reaction was carried out for 2 min and the mixture was stirred for 2 min. After adding the solvent to 3. OmL TFA / phenol / H20 (nu: nu: nu = 92: 5: 2.5) for 20 min, the mixture was treated with CH2C12 (2 X 3 mL) and DMF (4 x 3 mL), and the resin was washed with 3 mL of anhydrous DMF,Repeating the above condensation and deprotection steps (c) and (d) Until the synthesis of the peptide supported on the phenylhydrazine resin as shown in formula (8).(e)Amino acid condensation: A solution of 4-tert-butoxycarbonylamino-1-methyl-1H-imidazole-2-carboxylic acid (254 mg, 1.056 mmol) and triphosgene (BTC, 128 mg, 0.433 mmol) in 2 mL of anhydrous THF was added to the solution (Col 1 idine, 488yL, 3.696 mmol) was slowly added and the reaction immediately resulted in a large amount of white precipitate. After the reaction was added for 3 min, (5%, nu / nu), the white precipitate completely disappeared, and the reaction solution was transferred to the phenylhydrazine resin in which the protecting group was removed in step (b), N2 was bubbled and mixed, and the condensation reaction was carried out for 0.5 to 11 hours , The reaction solution was extracted, and the resin was washed with DMF (4 X 3 mL), Repeat the above condensation and deprotection steps () and (d), Until the synthesis of the peptide supported on the phenylhydrazine resin as shown in formula (9) is completed;(G) Gamma-amino acid condensation: A solution of R-2- (9-fluorenylmethoxycarbonylamino) -4-tert-butoxycarbonylaminobutyric acid (465 mg, 1.056 mmol) And triphosgene (128 mg, 0.433 mmol) Dissolved in 2 mL of anhydrous THF, To this solution was slowly added dropwise trimethylpyridine (488yL, 3.696 mmol) The reaction immediately resulted in a large amount of white precipitate, added to the reaction lmin, added HOAt (144 mg, 1.056 mmol) Then add 2mL DIEA / DMF solution (5%, nu / nu), reaction 5min, The white precipitate completely disappeared, and the reaction solution was transferred to a linear peptide supported on the phenylhydrazine resin represented by the formula (9) (NH2-Im-Im-Py-Py-phenylhydrazine resin), N2 bubbling, the condensation reaction was carried out for 0.5 to 11 hours, the reaction solution was extracted, The resin was washed with DMF (4 X 3 mL) to give a peptide supported on the phenylhydrazine resin represented by the formula (10)H) repeating the condensation and deprotection guard step (d) and (C), wherein the load until the completion of the synthetic peptides to give formula (11) in a phenylhydrazine of the resin;I) repeating the condensation and deprotection guard step (d) and (E), wherein the load until the completion of peptide synthesis to give the formula (12) in the resin phenylhydrazineJ) Condensation of terminal amino acids: 1-methyl-1H-imidazole-2-carboxylic acid (132 mg, 1.56pimol) and PyBOP (550 mg, 1.056 mmo 1) was dissolved in 3 mL of anhydrous DMF, DIEA (350 yL, 2.112 mmol) was added, and the reaction was carried out for 5 min. The reaction solution was transferred to the reaction represented by the formula (12) obtained in step (h) (2), and the reaction was carried out for 2 hours. The reaction solution was purged with N2, and the resin was washed with DMF (4 X 3 mL), and the compound represented by the formula (12) was removed by the step (b) in Example 1 A Fmoc protecting group supported on a phenylhydrazine resin to obtain a peptide supported on the phenylhydrazine resin represented by the formula (13)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Methyl-1H-imidazole-2-carboxylic acid, its application will become more common.

Reference:
Patent; Shenzhen Advanced Technology Institute; Su Wu; Wang Wei; Pan Zhengyin; Cheng Zhehong; Wu Chunlei; Fang Lijing; (36 pag.)CN106674209; (2017); A;,
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 616-47-7 as follows. Quality Control of 1-Methyl-1H-imidazole

In a 100-mL round bottom flask, a mixture of 1-methyl imidazole (0.1 mol, 8.21 g) and 1,4-butane sultone (0.1 mol, 11 mL) in toluene (30 mL) was refluxed for 24 h. The obtained white solid was washed with toluene (2910 mL) and dried under reduced pressure. Then, a stoichiometric amount of concentrated sulfuric acid (98 %) was added to the solid and the mixture was stirred for 24 h at 70 C to form the DAIL. It was then washed with diethyl ether (2*10 mL) and dried under vacuum.

According to the analysis of related databases, 616-47-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Rostamizadeh, Shahnaz; Zekri, Negar; Research on Chemical Intermediates; vol. 42; 3; (2016); p. 2329 – 2341;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 4331-29-7, The chemical industry reduces the impact on the environment during synthesis 4331-29-7, name is 1H-Benzo[d]imidazol-7-amine, I believe this compound will play a more active role in future production and life.

Benzoyl chloride (87muL, 0.75mmol) was added to a solution of 4-amino-1,3-benzodiazole32 (100mg, 0.75mmol) in anhydrous pyridine (1.0mL) at 0¡ãC, and the mixture was stirred for 12h at room temperature. After removal of the solvent, the residue was purified by silica gel column chromatography (MeOH/CHCl3, 1:20 to 1:10) to afford the products 8 (28mg, 16percent) and 9 (46mg, 18percent), each as a white solid. Compound 8: mp 183?185¡ãC; 1H NMR (500MHz, CDCl3/CD3OD, 99:1) delta 7.20 (dd, J=8.0, 8.0Hz, 1H), 7.26 (d, J=8.0Hz, 1H), 7.43 (dd, J=7.5, 7.5Hz, 2H), 7.50 (t, J=7.0Hz, 1H), 7.88 (s, 1H), 7.98 (d, J=7.5Hz, 2H), 8.03 (d, J=7.5Hz, 1H), 9.51 (br s, 1H); 13C NMR (125MHz, CDCl3/CD3OD, 99:1) delta 109.5, 113.1, 123.6, 127.4, 127.9, 128.7, 131.5, 132.0, 134.5, 135.7, 139.9, 166.8; FAB-MS m/z 238 (M+H)+. Compound 9: mp 152?154¡ãC; 1H NMR (500MHz, CDCl3) delta 7.46 (dd, J=8.0, 8.0Hz, 1H), 7.51 (dd, J=7.5, 7.5Hz, 2H), 7.55?7.62 (m, 3H), 7.70 (t, J=7.5Hz, 1H), 7.79?7.83 (m, 3H), 8.00 (d, J=8.5Hz, 2H), 8.16 (s, 1H), 8.54 (d, J=8.0Hz, 1H), 9.13 (br s, 1H); 13C NMR (125MHz, CDCl3) delta 110.7, 114.6, 127.0, 127.3, 128.9, 129.2, 129.7, 130.4, 132.2, 132.2, 132.8, 133.5, 134.4, 134.7, 141.8, 165.7, 167.1; FAB-MS m/z 342 (M+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, 1H-Benzo[d]imidazol-7-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Noguchi-Yachide, Tomomi; Sakai, Taki; Hashimoto, Yuichi; Yamaguchi, Takao; Bioorganic and Medicinal Chemistry; vol. 23; 5; (2015); p. 953 – 959;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 4857-06-1, 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. 4857-06-1 name is 2-Chloro-1H-benzo[d]imidazole, This 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.

General procedure: 2-Chloro-1H-benzoimidazole (3.04 g, 20 mmol) was dissolved in dry DMF (15 mL) at 0 C, to the solution was added NaH (0.91 g, 22.7 mmol), and the mixture was stirred for 1 h at 0 C, then halide (21.6 mmol) was added. The mixture was stirred overnight at room temperature and was poured into water (50 mL) and stirred for 1 h, filtrated, washed with water and dried to afford 4a-d.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-1H-benzo[d]imidazole, and friends who are interested can also refer to it.

Reference:
Article; Luo, Yu; Xiao, Feng; Qian, Shijing; Lu, Wei; Yang, Bo; European Journal of Medicinal Chemistry; vol. 46; 1; (2011); p. 417 – 422;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 104619-51-4, name is Di(1H-imidazol-1-yl)methanimine belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. Application In Synthesis of Di(1H-imidazol-1-yl)methanimine

To a solution of 22 (200 mg, 1.24 mmol) in freshly distilled THF (8 ml), was added 4-chloro-aniline(208 mg, 1.64 mmol). The mixture was stirred at room temperature for 24 h. The solvent was thenremoved under vacuum and the residue was purified on silica with 10% MeOH/DCM to yield theproduct as a white solid (240 mg, 1.09 mmol) in 88% yield.

The synthetic route of 104619-51-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Awuah, Emelia; Ma, Eric; Hoegl, Annabelle; Vong, Kenward; Habib, Eric; Auclair, Karine; Bioorganic and Medicinal Chemistry; vol. 22; 12; (2014); p. 3083 – 3090;,
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. 24134-09-6, name is 5-Bromo-1,2-dimethyl-1H-imidazole, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 24134-09-6

A 2.5 M solution of n-butyllithium in hexanes (0.260 mL, 0.650 mmol) was added dropwise to a dry ice-acetone cooled solution of 5-bromo-1,2-dimethyl-1H-imidazole (120 mg, 0.686 mmol) in tetrahydrofuran (2 mL). After 30 seconds, a solution of (4-chloro-2-methoxy-3-((4-(2,2,2-trifluoroethyl)piperazin-1-yl)methyl)quinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone (157 mg, 0.325 mmol, Intermediate 17: step b) in tetrahydrofuran (1 mL) was added dropwise by syringe. After 2 minutes, the flask was removed from the cooling bath. After 3 minutes, the flask was placed into an ice-water bath. After 45 minutes, water (20 mL) and ethyl acetate (50 mL) were added sequentially. The layers were separated. The organic layer was dried with sodium sulfate and the dried solution was filtered. Celite (7 g) was added to the filtrate and the mixture was concentrated in vacuo. The dry solid was loaded onto a silica gel column for flash-column chromatography. Elution with dichloromethane initially, grading to 10% methanol-dichloromethane provided impure title compound. Further purification by RP-HPLC eluting with 5% acetonitrile-water containing 0.2% TFA and partitioning of the combined fractions between dichloromethane-saturated aqueous sodium bicarbonate solution provided the title compound as a white solid. 1H NMR (500 MHz, CDCl3) delta ppm 8.20 (d, J=2.2 Hz, 1H), 7.72 (d, J=8.7 Hz, 1H), 7.41-7.34 (m, 1H), 7.12 (s, 1H), 6.05 (s, 1H), 5.89 (s, 1H), 4.09 (s, 3H), 3.91 (s, 3H), 3.88-3.80 (m, 2H), 3.37 (s, 3H), 2.99-2.87 (m, 2H), 2.65 (s, 8H), 2.24 (s, 3H); MS (ESI): mass calcd. for C26H30ClF3N8O2, 578.2. m/z found, 579.1 [M+H]+. (4-Chloro-2-methoxy-3-((4-(2,2,2-trifluoroethyl)piperazin-1-yl)methyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol was purified by chiral SFC (Chiralpak AD-H, 5 mum, 250 mm¡Á30 mm, mobile phase: 85% CO2, 15% isopropanol containing 0.2% isopropylamine) to provide two enantiomers. The first eluting enantiomer was Example 17b: 1H NMR (500 MHz, CDCl3) delta ppm 8.17 (d, J=2.1 Hz, 1H), 7.75 (d, J=8.7 Hz, 1H), 7.40-7.35 (m, 1H), 7.18 (s, 1H), 6.13 (s, 1H), 4.54 (s, 1H), 4.09 (s, 3H), 3.92 (s, 3H), 3.85 (s, 2H), 3.40 (s, 3H), 2.98-2.89 (m, 2H), 2.70-2.62 (m, 8H), 2.33 (s, 3H); MS (ESI): mass calcd. for C26H30ClF3N8O2, 578.2. m/z found, 579.1 [M+H]+ and the second eluting enantiomer was Example 17c: 1H NMR (500 MHz, CDCl3) delta ppm 8.16 (d, J=2.2 Hz, 1H), 7.77 (d, J=8.7 Hz, 1H), 7.41-7.36 (m, 1H), 7.20 (s, 1H), 6.16 (s, 1H), 4.16-4.06 (m, 4H), 3.93 (s, 3H), 3.86 (s, 2H), 3.41 (s, 3H), 2.98-2.88 (m, 2H), 2.71-2.61 (m, 8H), 2.35 (s, 3H); MS (ESI): mass calcd. for C26H30ClF3N8O2, 578.2. m/z found, 579.1 [M+H]+.

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 24134-09-6.

Reference:
Patent; JOHNSON & JOHNSON; LEONARD, KRISTI A.; BARBAY, KENT; EDWARDS, JAMES P.; KREUTTER, KEVIN D.; KUMMER, DAVID A.; MAHAROOF, UMAR; NISHIMURA, RACHEL; URBANSKI, MAUD; VENKATESAN, HARIHARAN; WANG, AIHUA; WOLIN, RONALD L.; WOODS, CRAIG R.; FOURIE, ANNE; XUE, XIAOHUA; CUMMINGS, MAXWELL D.; MCCLURE, KELLY; TANIS, VIRGINIA; US2015/111870; (2015); A1;,
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. 583-39-1, name is 2-Mercaptobenzimidazole, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 583-39-1

A mixture of benzimidazole-2-thione (7) (1.5 g, 10 mmol), triethylamine (2.88 g, 28.5 mmol), a catalytic amount (100 mg) of DMAP and anhydrous dichloromethane was stirred at room temperature for 10 min. A solution of acetyl chloride (2.83 g) and anhydrous dichloromethane was added dropwise and stirring was continued for 16 h. After diluting with water (100 ml) and dichloromethane (50 ml), the organic layer was separated, washed three times with an aqueous solution of potassium hydrogen sulfate (1 M, 50 ml) and water (50 ml) and dried over sodium sulfate. The solvent was removed under reduced pressure, and the product was purified by column chromatography on silica gel eluting with a 1:8 (v/v) mixture containing ethyl acetate and petroleum ether at 60-80 C to give a white solid. The product decomposes at ambient temperature and moisture to 1-acetylbenzimidazole-2-thione. Yield 1.3 g (5.55 mmol), 56%, white solid. Mp: 100-102 C (Mp: 102-103 C refPreviewPlaceHolder[40]). 1H NMR (CDCl3) delta 3.05 (s, 6H, OCH3), 7.31 (dd, 2H, 4J = 3.4 Hz, 3J = 6.3 Hz, H-5 and H-6), 7.97 (dd, 2H, 4J = 3.4 Hz, 3J = 6.3 Hz, H-4 and H-7). MS (EI) m/z 234 (M+). Anal. (C11H10N2O2S) C, H, N, S.

According to the analysis of related databases, 583-39-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Braun, Stephan; Botzki, Alexander; Salmen, Sunnhild; Textor, Christian; Bernhardt, Guenther; Dove, Stefan; Buschauer, Armin; European Journal of Medicinal Chemistry; vol. 46; 9; (2011); p. 4419 – 4429;,
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 85692-37-1 as follows. Formula: C6H8N2O

1-Methyl-2-acetylimidazole (1.8 g, 16.36 mmol) and LiOH (392 mg, 16.36 mmol) were stirred in MeOH (100 mL) before methyl 4-formylbenzoate (2.6 g, 16.36 mmol) was added. After 30 min a thick yellow precipitate was formed. The precipitate was filtered and dried under vacuum to yield 2c as a yellow solid (63%).

According to the analysis of related databases, 85692-37-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Jacob, Nicholas T.; Miranda, Pedro O.; Shirey, Ryan J.; Gautam, Ritika; Zhou, Bin; de Orbe Izquierdo, M. Elena; Hixon, Mark S.; Hart, Jonathan R.; Ueno, Lynn; Vogt, Peter K.; Janda, Kim D.; Bioorganic and Medicinal Chemistry; vol. 26; 14; (2018); p. 4234 – 4239;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 98873-55-3,Some common heterocyclic compound, 98873-55-3, name is 2-(1H-Imidazol-1-yl)acetonitrile, molecular formula is C5H5N3, 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 stirred solution of 2-(lH-imidazol-l-yl)acetonitrile (400 mg, 3.73 mmol) in dimethylsulfoxide (5 mL), potassium hydroxide (461 mg, 8.22 mmol) was added at 0 C and stirred for 30 min at 25 C. To this reaction mixture, carbon disulfide (0.29 mL, 4.85 mmol) was added and stirred for another 15 min. 5,6-Dichloropyrazine-2,3-dicarbonitrile (743 mg, 3.73 mmol) was added portion- wise to the reaction mixture and allowed to stir for 2 h at 25 C. After completion of the reaction, water was added to the reaction mixture and the product was extracted twice with ethyl acetate (50 mL). Ethyl acetate layer was washed with brine (50 mL), dried over anhydrous sodium sulphate, filtered and evaporated under reduced pressure to obtain a crude product. The crude product was then purified by column chromatography on silica gel (eluent-hexane to 40% ethyl acetate in hexane) to obtain 2-(cyano(lH-imidazol-l-yl)methylene)-[l,3]dithiolo[4,5-b]pyrazine-5,6-dicarbonitrile (350 mg, 1.31 mmol, 30% yield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(1H-Imidazol-1-yl)acetonitrile, its application will become more common.

Reference:
Patent; PI INDUSTRIES LTD.; SAXENA, Rohit; PUJARI, Sandip Appaji; THOK, Sambhaji Shivnath; DEBNATH, Sankha; RAJU, Jella Rama; MISHRA, Rupesh Kumar; GARG, Ruchi; AUTKAR, Santosh Shridhar; VENKATESHA, Hagalavadi M; KLAUSENER, Alexander G.M.; (110 pag.)WO2019/150311; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 33543-78-1,Some common heterocyclic compound, 33543-78-1, name is Ethyl 1H-imidazole-2-carboxylate, molecular formula is C6H8N2O2, 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 mixture of ethyl 1H-imidazole-2-carboxylate (700?mg, 5.0?mmol), potassium carbonate (1.38?g, 10.0?mmol) and 4-bromobut-1-ene (800?mg, 6.0?mmol) in 5?mL DMF was heated to 80?C for 3?h. TLC analysis indicated that the reaction had ceased. After cooling to room temperature, the solution was diluted with EtOAc (15?mL) and washed with water (25?mL?*?3), brine (25?mL?*?3). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was then purified by SiO2 chromatography (ethyl acetate: petroleum ether?=?1:1) to give compound 9d as colorless oil (0.93?g, 96%). 1 H NMR (500?MHz, CDCl3) delta 7.14 (d, J?=?1.0?Hz, 1H), 7.05 (d, J?=?1.0?Hz, 1H), 5.80-5.70 (m, 1H), 5.08-5.01 (m, 2H), 4.47 (t, J?=?7.0?Hz, 2H), 4.41 (q, J?=?7.0?Hz, 2H), 2.59-2.50 (m, 2H), 1.43 (t, J?=?7.0?Hz, 3H); ESI-MS: m/z = 195 [M+H]+.

The synthetic route of 33543-78-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Yu, Jianjun; Liu, Jieyu; Li, Daqiang; Xu, Lei; Hong, Duidui; Chang, Shan; Li, Jia; Liu, Tao; Zhou, Yubo; European Journal of Medicinal Chemistry; vol. 164; (2019); p. 423 – 439;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem