Category: imidazoles-derivatives

Some common heterocyclic compound, 41716-18-1, name is 1-Methyl-1H-imidazole-4-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. HPLC of Formula: C5H6N2O2

General procedure: To a solution of 1-methyl-1Himidazole-4-carboxylic acid (0.50 g, 4.0 mmol), 1-hydroxybenztriazole monohydrate (0.74 g, 4.8 mmol), and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.92 g, 4.8 mmol) in acetonitrile (10 mL) was added a solution of 3-(trifluoromethoxy) benzylamine 8(0.84 g, 4.4 mmol) in acetonitrile (10 mL), and the mixture was stirred at room temperature for overnight. The reaction mixture was concentrated in vacuo, and saturated aqueous NaHCO3solution was added to the residue. After extraction with ethyl acetate, the organic layer was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified using silica gel column chromatography (0?10percent MeOH in CHCl3) to obtain 9(1.18 g, 98percent) as a colorless powder

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 41716-18-1, its application will become more common.

Reference:
Article; Yamamoto, Shuji; Ohta, Hiroshi; Abe, Kumi; Kambe, Daiji; Tsukiyama, Naohiro; Kawakita, Yasunori; Moriya, Minoru; Yasuhara, Akito; Chemical and Pharmaceutical Bulletin; vol. 64; 11; (2016); p. 1630 – 1640;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 15813-09-9, 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. 15813-09-9 name is 4,5-Diiodo-1H-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.

Step b: 4-(4-iodo- lH-imidazol-5-yl)tetrahydro-2H-pyran-4-ol[0548] ft-BuLi (2.5 M, 24.8 mL, 62.0 mmol) was added to a solution of 4,5-diiodo-lH-imidazole (9.6 g, 30.0 mmol) in THF (100.0 mL) at -78C and the mixture was stirred at -78C for 30 min. Dihydro-2H-pyran-4(3H)-one (6.0 g, 60.0 mmol) was added and the reaction mixture was stirred at -78C for 10 min and then allowed to warm to room temperature over 1 h. Saturated NH4C1 solution was added and the resulting mixture was extracted with ethyl acetate. The combined extracts were washed with brine, dried over anhydrous Na2S04 and concentrated. The residue was purified by flash column chromatography on silica gel (PE to PE/EA = 1 : 1 to DCM/MeOH = 50: 1) to give 2.7 g of the title compound as a white solid (30%> yield).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4,5-Diiodo-1H-imidazole, and friends who are interested can also refer to it.

Reference:
Patent; ZENOBIA THERAPEUTICS, INC.; BOUNAUD, Pierre-Yves; NIENABER, Vicki; STEENSMA, Ruo, W.; LOWE, John, A., III; WO2012/178015; (2012); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 33468-67-6, These common heterocyclic compound, 33468-67-6, name is 2-Methyl-4-(trifluoromethyl)-1H-imidazole, 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 42 Synthesis of (S)-l-(l-(4-chlorophenyl)-5-isopropyl-lH-pyrazol-4-yl)-3-(2-methyl-4- (trifluoromethyl)-lH-imidazol-l-yl)pyrrolidin-2-one and ( ?)-l-(l-(4-chlorophenyl)-5- isopropyl-lH-pyrazol-4-yl)-3-(2-methyl-4-(trifluoromethyl)-lH-imidazol-l- yl)pyrrolidin-2-one step e [0203] a) To a solution of a-bromo-y-valerolactone (19.8 g, 120 mmol) and 2-methyl-4- (trifluoromethyl)- lH-imidazole (4.50 g, 30 mmol) in acetonitrile (60 mL) was added K3PO4 (19.1 g, 90 mmol). The slurry was heated to 80 C for 2 days, then cooled to room temperature, diluted with EtOAc (200 mL), filtered through Celite, and concentrated. The residue was purified by flash chromatography (S1O2, 0 – 3.5% methanol/CH2Cl2) to give the product as a pasty colorless solid. [0204] b) A mixture of the lactone intermediate (700 mg, 5.1 mmol) from step a and (5)- phenylglycinol (1.09 g, 4.64 mmol) was heated at 80 C for 18 h, cooled to room temperature, and purified by flash chromatography (Si02, 0.5-2% methanol/EtOAc) to give two diastereomeric products as colorless foams. The first eluting isomer (310 mg) was obtained in 99: 1 diastereomeric ratio (XH NMR) and the second eluting isomer (200 mg) in 1 1 : 1 diastereomeric ratio (XH NMR). Each diastereomer was carried through steps c and d independently. [0205] c) To a mixture of the product from step b (186 mg, 0.5 mmol) in dioxane (2 mL) was added 6 M H2S04 (1.25 mL, 7.5 mmol). The resulting slurry was heated at 80 C for 1 h, cooled to room temperature, and purified by reverse phase HPLC (CI 8 column, acetonitrile-H20 with 0.1% TFA as eluent). The resulting lactone FontWeight=”Bold” FontSize=”10″ TFA salt was neutralized to provide a colorless solid (53 mg, 0.23 mmol) that was used without further purification. [0206] d) A mixture of the lactone product from step c and l-(4-chlorophenyl)-5- isopropyl- lH-pyrazol-4-amine (50 mg, 0.21 mmol) in 1 ,2-dichloroethane (1 mL) was treated with AlMe3 (2 M solution in toluene, 210 mu, 0.42 mmol) at room temperature for 30 min. The reaction was quenched with saturated NH4C1 (5 mL) and extracted with EtOAc (3 x 3 mL). The organic layer was dried on MgS04, filtered, concentrated, and purified by flash chromatography (Si02, 0 – 100% EtOAc/CH2Cl2) to give the desired product (50 mg, 0.1 mmol, 50% yield). [0207] e) The product from step d (50 mg, 0.1 mmol) in dichloromethane (0.5 mL) was treated with Et3N (40 mu, 0.29 mmol) and methanesulfonyl chloride (20 mu, 0.23 mmol) for 30 min at room temperature. The mixture was then diluted with 1,2-dichloroethane (1 mL) and washed with water (1 mL). The organic layer was dried on Na2S04 and filtered. To the filtrate was added triethylamine (100 mu^, 0.7 mmol) and the mixture was stirred at 65 C for 90 min, concentrated, and purified by reverse phase HPLC (CI 8 column, acetonitrile-H20 with 0.1% TFA as eluent). The resulting TFA salt was neutralized to provide the titled compound (19 mg, 0.041 mmol) as a white solid. XH NMR (400 MHz, CDC13) delta 7.55 (s, 1 H), 7.48 (d, J= 8.6, 2 H), 7.36 (d, J= 8.6, 2 H), 7.22 (d, J= 0.8 Hz, 1 H), 5.07 (dd, J= 10.5, 8.9 Hz, 1 H), 3.91-3.77 (m, 2 H), 3.05 (hept, J= 7.0 Hz, 1 H), 2.90-2.82 (m, 1 H), 2.52 (s, 3 H), 2.42-2.31 (m, 1 H), 1.24 (d, J= 3.2 Hz, 3 H), 1.23 (d, J= 3.2 Hz, 3 H); MS: (ES) m/z calculated for C2iH22ClF3N50 [M + H]+ 452.1, found 451.9. The titled compounds were analyzed by chiral normal phase chromatography (Regis Cell cat 784104, 25 cm x 4.6 mm, 5 micron; eluent: 0.1% diethylamine/IPA, 0.6 ml/min). The (5)-enantiomer generated from the first-eluting diasteromer from step b had a retention time of 6.8 min (isolated in 8: 1 er). The (R)-enantiomer generated from the second-eluting diasteromer from step b had a retention time of 7.3 min (isolated in 78: 1 er).

Statistics shows that 2-Methyl-4-(trifluoromethyl)-1H-imidazole is playing an increasingly important role. we look forward to future research findings about 33468-67-6.

Reference:
Patent; CHEMOCENTRYX, INC.; CHEN, Xi; FAN, Pingchen; LI, Yandong; POWERS, Jay P.; MALATHONG, Viengkham; PUNNA, Sreenivas; TANAKA, Hiroko; ZHANG, Penglie; WO2014/89495; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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. 3012-80-4, name is 1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde, A new synthetic method of this compound is introduced below., HPLC of Formula: C9H8N2O

[3-] [{5- [1- ( 1-METHYL-LH-BENZOIMIDAZOL-2-YLMETHYL)-PIPERIDIN-2-YL]- [1,] 2,4] [OXADIAZOL-3-YL}-] benzonitrile (63 mg, 79.1percent) was obtained from [3- (5-PIPERIDIN-2-YL- [1,] 2,4] oxadiazol-3-yl) – benzonitrile (50.8 mg, 0.2 mmol) with [1-METHYL-2-FORMYLBENZIMIDAZOLE] (32 mg, 0.2 mmol), sodium triacetoxyborohydride (59.3 mg, 0.28 mmol) and dichloroethane (1 mL) at room temperature for 5 [MIN. 1H] NMR [(CDC13),] 8 (ppm): 8. 30 (s, 1H), 8.27 (d, 1H), 7.76 (d, 1H), 7.62 (d, 1H), 7.59 (t, 1H), 7.30 (d, 1H), 7.20 (m, 2H), 4.02 (t, 1H), 3.90 (dd s, [SH),] 3.00 (m, 1H), 2.43 (m, 1H), 2.01 (s, 2H), 1.48-1. [88] (m, 4H).

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; ASTRAZENECA AB; NPS PHARMACEUTICALS, INC.; WO2004/14902; (2004); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 288-32-4, The chemical industry reduces the impact on the environment during synthesis 288-32-4, name is 1H-Imidazole, I believe this compound will play a more active role in future production and life.

Part B: To the dichloromethane solution of the hydroxyethyl compound of Part A (1 g, 1.9 mmol) was added thionyl chloride (3.8 mmol) and reaction solution was stirred at ambient temperature for 12 hours. Concentration in vacuo provided the chloride as a light yellow gel. To the solution of the chloride and potassium carbonate (0.54 g, 3.8 mmol) in N,N-dimethylformamide (5 mL) was added imidazole (0.4 g, 5.7 mmol) and solution was stirred at ambient temperature for 12 hours. Then N,N-dimethylformamide was evaporated under high vacuum and the residue was diluted with ethyl acetate. The organic layer was washed with water and dried over magnesium sulfate. Concentration in vacuo and chromatography on silica eluding with ethyl acetate/hexane provided the imidazole ethyl ester as a light yellow gel (0.82 g, 75.2percent).

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-Imidazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Pharmacia Corporation; US6750228; (2004); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 14741-71-0, 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. 14741-71-0, name is Ethyl 2-(1H-benzo[d]imidazol-2-yl)acetate, This compound has unique chemical properties. The synthetic route is as follows.

Example 37: Synthesis of 3-Fluoro-l,7,llb-triaza-benzo[c]fluorene-6-carboxylic acid ethyl es [0321] To a solution of compound SMI (0.8 g, 5 mmol) and compound SM2 (1.02 g, 5 mmol) in ethanol (50 mL) was added piperidine (1.28 g, 15 mmol) and the mixture was stirred at room temperature for 20 min. The reaction mixture was heated to reflux for 16h. After cooling, the mixture was filtered and washed with ethanol, dried to get compound 7A as yellow solid (0.82 g, 79 yield). LCMS: m/z 309.9 (M+H)+.

The chemical industry reduces the impact on the environment during synthesis Ethyl 2-(1H-benzo[d]imidazol-2-yl)acetate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; HADDACH, Mustapha; WO2015/172123; (2015); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 4856-97-7, These common heterocyclic compound, 4856-97-7, name is (1H-Benzoimidazol-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.

A mixture of NiCl2*6H2O (0.238 g, 1 mmol), HL1 (0.074 g,0.5 mmol), acetonitrile (4 mL) and ethanol (4 mL), with a pHadjusted to 7.5 by addition of triethylamine, was poured into aTeflon-lined autoclave (15 mL) and then heated at 160 ¡ãC for 3 days. Green crystals of 1 were collected by filtration, washed with ethanol and dried in air. Phase pure crystals of 1 were obtained by manual separation (yield: 89.5 mg, ca. 63.4percent based onthe HL1 ligand). Anal. Calc. for 1: C40H40Cl4N12Ni4O4(Mr = 1129.40), Calc.: C, 42.54; H, 3.57; N, 14.88. Found: C, 42.51;H, 3.59; N, 14.91percent. IR data for 1 (KBr, cm1): 3425 s, 1274 m,1458 s, 1069 s, 1280 m, 600 m, 467 m.

The synthetic route of 4856-97-7 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Yang, Li; Zhang, Shu-Hua; Wang, Wei; Guo, Jing-Jing; Huang, Qiu Ping; Zhao, Ru-Xia; Zhang, Chun-Lian; Muller, Gilles; Polyhedron; vol. 74; (2014); p. 49 – 56;,
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. 17289-25-7, name is (1-Methyl-1H-imidazol-4-yl)methanol belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. SDS of cas: 17289-25-7

To a solution of intermediate 1 (5g, 44.64 [MMOL)] in CH2CI2 [(10 MI)] at [0¡ãC] was added dropwise thionyl chloride (50 [ML)] and then the mixture was stirred at room temperature overnight and then under reflux for 3 hours and then concentrated under reduced pressure. The residue was treated with diethyl oxide and the resulting precipitate was filtered and dried. The title compound was obtained as a brown solid [(4G,] 53. 80percent); 1HNMR (300 MHz, [DS-DMSO, PPM). S] : 9.25 (s , 1H), 7.8 (s, 1H), 4.95 (s, 2H), 3.9 (s, 3H).

The synthetic route of 17289-25-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2004/13134; (2004); A2;,
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 4857-06-1 as follows. name: 2-Chloro-1H-benzo[d]imidazole

2-Chlorobenzimidazole (10 g, 65.56 mmol)was dissolved in 80 ml of 2.5N NaOH (175 mM) and dimethyl sulfate (11.0 mL, 116 mM) wasadded drop wise under stirring at room temperature. After the addition the mixture was stirredfor further 2 h and the precipitate formed was filtered by suction and the product washed severaltimes with ice-water mixture till the filtered solution was neutral. Petrol ether was suckedthrough the solid product several times and then dried in vacuo to afford a light brown solid(8.76 g, 81% yield). 1H NMR (200 MHz, d6-DMSO, delta): 3.78 (s, 3H, CH3), 7.26 (dq, J = 1.2Hz,J = 7.4Hz, BZI-H5/H6), 7.54-7.60 (m, 2H, BZI-H4/H7).

According to the analysis of related databases, 4857-06-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Wang, Lei; Kofler, Marina; Brosch, Gerald; Melesina, Jelena; Sippl, Wolfgang; Martinez, Elisabeth D.; Easmon, Johnny; PLoS ONE; vol. 10; 12; (2015);,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 221289-88-9,Some common heterocyclic compound, 221289-88-9, name is 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile, molecular formula is C8H5N3O, 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 suspension of 2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile (XVTI, 1.19 g, 7.48 mmol, 1 equiv) in acetonitrile (5 mL) was added phosphorus(v) oxy chloride (1.398 mL, 14.95 mmol). The reaction was stirred at 1 10 C for 16 hours, then cooled to room temperature. It was diluted with acetonitrile and then slowly added to a cold, rapidly -stirring beaker of saturated aqueous sodium bicarbonate (50 mL). The mixture was extracted with ethyl acetate; which was dried over anhydrous magnesium sulfate, filtered, and concentrated to provide 2~chloro-1H-benzo d]imidazole~6-carbonitrile as a tan powder. (ESI, pos. ion) m/z: 178.2 [M+i]

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile, its application will become more common.

Reference:
Patent; AMGEN INC.; BARTBERGER, Michael D.; CHAKKA, Nagasree; GAO, Hua; GUZMAN-PEREZ, Angel; HORNE, Daniel B.; HUA, Zihao; KIEFFER, Madeleine; LIN, Daniel C. H.; MILGRAM, Benjamin Charles; PANTELEEV, Jane; SCHENKEL, Laurie; STELLWAGEN, John; WEISS, Matthew; WHITE, Ryan D.; ZHAO, Wei; (345 pag.)WO2019/79578; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem