Author: Jessica.F

Some common heterocyclic compound, 5098-11-3, name is 5-Amino-1H-imidazole-4-carbonitrile, molecular formula is C4H4N4, 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. Application In Synthesis of 5-Amino-1H-imidazole-4-carbonitrile

Example 46: General procedure for the preparation of 4-fluoro-benzoyl- imidazo[1 ,5-a]pyrimidines of general formula (I) following Scheme 1. N-[3-[8-(4-fluoro-benzoyl)-imidazo[1 ,5-a]pyrimidin-4-yl]-phenyl]-N-methyl- methanesulfonamide Part A EPO A solution of 4-fluoro-phenyl magnesium bromide was prepared from 1.0 g ( 42 mmol) of magnesium and 7.9 g (42 mmol) of 1-bromo-4-fluoro-benzene in 40 ml of dry tetrahydrofuran.To the solution of the Grignard reagent, cooled by an ice-salt bath, a mixture of 1 g (9.3 mmol)of 5-amino-1 H-imidazole-4-carbonitrile and 20 ml of dry tetrahydrofuran was slowly added with stirring. After standing at room temperature for 2 hours, the mixture was cooled and decomposed by adding, with stirring, 40 ml of 3M hydrochloric acid. When the decomposition was completed (1 hour at a temperature between 90-950C), the reaction mixture was basified to ph 10 with 25% ammonium hydroxide and was extracted with methylene chloride. The solution was dried with anhydrous sodium sulfate and the methylene chloride was distilled under diminished pressure to yield an oil which was chromatographied (silica gel) using methylene chloride/methanol as eluent to produce 1.16 g (yield 62%) of (5-amino-1 H- imidazol-4-yl)-(4-fluoro-phenyl)-methanone.1H NMR (400 MHz, DMSO): 6.86 (2H, b), 7.14-7.29 (3H, m), 8.44 (2H, b),11.56 (1 H, b).MS (ES) m/z = 206 (MH+)HPLC = 96.8%

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5098-11-3, its application will become more common.

Reference:
Patent; FERRER INTERNACIONAL, S. A.; WO2006/84835; (2006); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 147359-76-0, name is Flibanserin Hydrochloride, belongs to imidazoles-derivatives compound, 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 147359-76-0, Quality Control of Flibanserin Hydrochloride

44 L of ethanol and 300 kg of water were added to the autoclave, followed by the addition of 22 kg of compound V (fluoropancaline hydrochloride)After heating, the temperature was 80 C. After the solid was completely dissolved, the anhydrous potassium carbonate solution (11. 7 kg of anhydrous potassium carbonate was dissolved in 96 kg of water) was added dropwise and incubated at 80 C for 2 hours.Cooled to room temperature, stirred for 3 hours, filtered, filtered at 50 C for 5 hours,Finished product 18. 61 kg, yield 92.5%, HPLC purity 99. 95%

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Flibanserin Hydrochloride, and friends who are interested can also refer to it.

Reference:
Patent; Shandong Cheng Chuang Pharmaceutical Development Co., Ltd.; Guo Zhenxing; Lv Zhitao; Yao Songzhi; Li Shujin; (12 pag.)CN106749038; (2017); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 84712-08-3,Some common heterocyclic compound, 84712-08-3, name is 5-Bromo-1-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one, molecular formula is C8H7BrN2O, 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.

Step 2: Synthesis of Intermediate 1-27.2 1-27.1 (4.41g, 19.42 mmol) and phosphoroxybromide (27.84g, 97.11 mmol) are stirred at 100C for 3h. The reaction mixture is diluted with iced water. The precipitate is filtered off and triturated with DIPE. Yield 89%

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

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; ANDERSKEWITZ, Ralf; GRAUERT, Matthias; GRUNDL, Marc; HAEBEL, Peter, Wilhelm; OOST, Thorsten; PAUTSCH, Alexander; PETERS, Stefan; BINDER, Florian; VINTONYAK, Viktor; WO2014/140075; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 37619-25-3, A common heterocyclic compound, 37619-25-3, name is Methyl 1H-benzo[d]imidazole-4-carboxylate, molecular formula is C9H8N2O2, 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 solution of BnBr (1.11 g, 6.6 mmol) in DMF (1.5 mL) was added dropwise to a solution of the compound Int-40 (880 mg, 5 mmol) in DMF (10 mL) at 0~5 C. The reaction was allowed to warm to room temperature and was stirred for 15 h. The mixture was partitioned between ethyl acetate and water. The organic phase was washed with water and brine, dried over NaiSCri and concentrated under reduced pressure. The crude product was purified by column chromatography (hexanes/ ethyl acetate:3/l) to afford the compound Int-41 (600 mg, 45%) as a yellow solid. NMR (400 MHz, CDCh): d 3.74 (s, 3H), 5.75 (s, 2H), 6.93-6.95 (m, 2H), 7.20-7.24 (m, 3H), 7.28 (t, J = 8.0 Hz, 1H), 7.71 (dd, J = 0.8, 8.0 Hz, 1H), 8.00 (dd, J = 0.8, 8.0 Hz, 1H), 8.07 (s, 1H). ESI-MS (EI+, m/z) : 267.15.

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; DANA-FARBER CANCER INSTITUTE, INC.; GRAY, Nathanael; ZHANG, Tinghu; FISCHER, Eric; VERANO, Alyssa; HE, Zhixiang; DU, Guangyan; DONOVAN, Katherine; NOWAK, Radoslaw; YUAN, Christine; LIU, Hu; (0 pag.)WO2020/6233; (2020); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 378203-86-2, name is Ethyl 1-methyl-4-nitro-1H-pyrazole-3-carboxylate, belongs to imidazoles-derivatives compound, 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 378203-86-2, HPLC of Formula: C7H9N3O4

Intermediate 44b) A degassed solution of intermediate 44a (480 mg), 2-bromo-1 ,4-dimethoxybenzene (1.04 g), palladium acetate (54 mg), di(1 -adamantyl)-n-butylphosphine (130 mg) and potassium acetate (490 mg) in N,N- dimethyl acetamide (7 mL) was stirred under an argon atmosphere at 150 C for 2 h. The volatiles were removed under reduced pressure and the residue was dissolved in water and was extracted with CH2CI2. The combined organic layers were dried and the volatiles were removed under reduced pressure. The residue was purified by column chromatography (Si02/ 50 g, Cy / 2-propanol) to yield the desired compound (31 % yield). LC-MS {Method 1): m/z [M+H]+ = 336.2 (MW calc. = 335.31 ); R, = 3.4 min

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 1-methyl-4-nitro-1H-pyrazole-3-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; GRUeNENTHAL GMBH; NORDHOFF, Sonja; WACHTEN, Sebastian; KLESS, Achim; VOSS, Felix; RITTER, Stefanie; WO2014/108336; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

93668-43-0, name is 2-(1H-Imidazol-1-yl)ethanamine dihydrochloride, belongs to imidazoles-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. name: 2-(1H-Imidazol-1-yl)ethanamine dihydrochloride

To a stirred solution of 2-(1H-imidazol-1-yl)ethan-1-amine dihydrochloride (commercially available from Sigma Aldrich) (600 mg, 3.25 mmol) in DMF (5 mL) was added DIPEA (2.2 mL, 13.0 mmol) at 0 C. After 15 min, tert-butyl N-[(1E)-{[(tert-butoxy)carbonyl]amino}(1H-pyrazol-1-yl)methylidene]carbamate (commercially available from Sigma Aldrich) (1.1 g, 3.58 mmol) was added at the same temperature and allowed to stir at RT for 16 h. N2 gas was bubbled into the reaction mixture for 15 minutes then water was added to the crude product followed by stirring for 5 minutes. The resulting precipitate was filtered, washed with water (2 x 10 mL) and dried under high vacuum affording a white solid (800 mg, 71%). M/z 354.2 [M+H]+

The synthetic route of 93668-43-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Antabio SAS; DAVIES, David; LEIRIS, Simon; (56 pag.)EP3572411; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 24134-65-4, 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 24134-65-4 as follows.

A solution of lambda/-methyl-lambda/-[2-(methylamino)ethyl]- 3,4-bis(methyloxy)benzenesulfonamide (50 mg; 0.17 mmol), prepared as Example 10a, and DIEA (43 uL; 0.25 mmol) in 2 mL of DCM was treated with 1 ,3-dimethyl-2- oxo-2,3-dihydro-1 /-/-benzimidazole-5-sulfonyl chloride (47 mg; 0.18 mmol). The solution was capped under nitrogen and stirred at room temperature overnight. The reaction was diluted to 10 mL with DCM and washed once each with 1 M NaHSO4, water, and sat’d aq. NaHCO3. The organic phase was dried over Na2SO4 and concentrated in vacuo to give 87 mg of the title compound as white amorphous solid. 92% purity by HPLC. LCMS (M+H = 513). 1 H NMR (DMSO-d6) delta 7.49 (m, 2H), 7.32 (m, 2H), 7.14 (m, 2H), 3.82 (s, 3H), 3.80 (s, 3H), 3.38 (s, 3H), 3.36 (s, 3H), 3.07 (bs, 4H), 2.67 (s, 3H), 2.66 (s, 3H).

According to the analysis of related databases, 24134-65-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2007/127505; (2007); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 279226-70-9, 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. 279226-70-9, name is 1-Methyl-1H-benzimidazole-5-carboxaldehyde belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

A suspension of 6-(l-methyl-lH-pyrazol-4-yl)-4-(6-(piperazin-l-yl)pyridin-3- yl)pyrazolo[l,5-a]pyrazine-3-carbonitrile dihydrochloride (Example 8; 30 mg, 0.078 mmol) in DCE (778 mu.) was treated sequentially with 1 -methyl- lH-benzimidazole-5-carboxaldehyde (25 mg, 0.16 mmol) and NaBH(AcO)3 (49 mg, 0.23 mmol). The mixture was stirred overnight at ambient temperature, and then concentrated in vacuo. The residue was purified first by silica chromatography (using 0-20% MeOH in DCM as the gradient eluent) and then by C18 reverse phase chromatography (using 5-95% ACN/water with 0.1% TFA the gradient eluent) to cleanly afford the title compound as its TFA salt. The TFA salt was treated with saturated NaHCCb(aq), and subsequently extracted into EtOAc (3x). The combined organic extracts were dried over anhydrous Na2S04(S), filtered, and concentrated in vacuo to cleanly afford the title compound (1.5 mg, 3.6% yield). MS (apci) m/z = 529.8 (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, 1-Methyl-1H-benzimidazole-5-carboxaldehyde, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ANDREWS, Steven W.; BLAKE, James F.; HAAS, Julia; JIANG, Yutong; KOLAKOWSKI, Gabrielle R.; MORENO, David A.; REN, Li; WALLS, Shane M.; (421 pag.)WO2018/136661; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 72459-45-1, A common heterocyclic compound, 72459-45-1, name is 1-(2-Bromobenzyl)-1H-imidazole, molecular formula is C10H9BrN2, 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 7 (COMPOUND 7) 2-Bromophenyl-1-(1-hydroxycycloheptyl)-1-imidazolylmethane A solution of lithium diisopropylamide in 100 ml of tetrahydrofuran was prepared at -30 C. from 5.1 g (50 mmol) of diisopropylamine and 30 ml (50 mmol) of n-butyllithium in hexane. 11.85 g (50 mmol) of N-(2-bromobenzyl)-imidazole were added dropwise to this solution at -78 C., stirring was carried out for half an hour and 5.6 g (50 mmol) of cycloheptanone were then added at this temperature. The reaction mixture was warmed up to room temperature in the course of 3 hours and worked up with water and methylene chloride. 12 g of crude product were obtained, and this product gave 5.5 g of an imidazole derivative of melting point 108 C. after recrystallization with cyclohexane/ethyl acetate.

The synthetic route of 72459-45-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hoechst Aktiengesellschaft; US4876354; (1989); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 93668-43-0, These common heterocyclic compound, 93668-43-0, name is 2-(1H-Imidazol-1-yl)ethanamine dihydrochloride, 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.

In like manner, the reaction of 1H-imidazole-1-ethaneamine dihydrochloride with 2-furoyl chloride by the procedure of Example 1 provided N-[2-(1H-imidazol-1-yl)ethyl]-2-furanecarboxamide, m.p. 131-133 C.

Statistics shows that 2-(1H-Imidazol-1-yl)ethanamine dihydrochloride is playing an increasingly important role. we look forward to future research findings about 93668-43-0.

Reference:
Patent; American Cyanamid Company; US4489089; (1984); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem