Month: June 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. 51605-32-4, name is Ethyl 5-methyl-1H-imidazole-4-carboxylate, A new synthetic method of this compound is introduced below., Product Details of 51605-32-4

To a mixture of ethyl 4-methyl-1H-imidazole-5-carboxylate (7.30 g, 45.9 mmol) in THF (60 mL) is added MeOH (2.23 mL, 55.1 mmol) and triphenylphosphine (14.8 g, 55.1 mmol). The reaction is cooled to 0° C. under N2 and diethyl azodicarboxylate (9.0 mL, 17.6 mmol) is added dropwise. The mixture is warmed to room temperature and stirred overnight. The volatiles are evaporated in vacuo. Ether (50 mL) is added. The mixture is stirred at room temperature for 30 minutes, filtered, the filter cake is washed with ether (50 mL). The filtrate and ether washings are combined and are sequentially washed with water (30 mL) and brine (30 mL). The organic phase is dried over Na2SO4, evaporated in vacuo to provide the crude product. The crude product is subjected to silica gel flash column eluting with 30percent EtOAc in hexanes to EtOAc to give the title compound (5.13 g, 59.8percent) as a yellow oil. LC/MS (m/z): 169 (M+H).

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; Eli Lilly and Company; Hu, Zhi Long; Liu, Lian Zhu; Ma, Tianwei; Zhang, Haizhen; Zhou, Jingye; (25 pag.)US2018/194755; (2018); 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. 2963-77-1, name is 4-(1H-Benzo[d]imidazol-2-yl)aniline, A new synthetic method of this compound is introduced below., Quality Control of 4-(1H-Benzo[d]imidazol-2-yl)aniline

General procedure: The mixture of 0.1mol of phenoxy acetic acid derivative(PAA1-PAA5) and 0.1mol of dicyclohexyl carbodiimide in10 mL dichloromethane was stirred at room temperature.After 30 minutes, a solution of AB or APB in 20 ml of dichloromethaneand 5 ml of pyridine was added. The reactionmixture was stirred initially at 0C for 2 h followed by stirring at room temperature for 12 h. The precipitated dicyclohexylureawas removed by filtration and the solvent wasdistilled at reduced pressure on rotary vacuum evaporator.The dried product was dissolved in ethyl acetate (10 mL) andthe solution was washed with 10% aqueous solution of sodiumbicarbonate followed by distilled water to remove thetraces of residual dicyclohexylurea. The ethyl acetate layerwas dried with anhydrous magnesium sulphate and then solventwas distilled off to obtain the crude product which wasrecrystallized from ethanol-water mixture.

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:
Article; Singh, Gurmeet; Bansal, Yogita; Bansal, Gulshan; Goel, Rajesh Kumar; Medicinal Chemistry; vol. 10; 4; (2014); p. 418 – 425;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 139481-72-4, 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. 139481-72-4 name is Trityl candesartan, 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.

Example 15: Deprotection without Acid; A solution of trityl candesartan c (TCS, 350 g, 410.3 mmol), toluene (1050 mL), methanol (2100 mL) and water (17.0 mL) was refluxed for about 2-4 h (HPLC control), the solvents were evaporated at 40-50 C/P<100 mbar to give a residue as a viscous oil, the residue was dissolved at 45-55 C in a mixture of Toluene/Methanol (1041g, 95: 5, w/w) to give a clear solution. The solution was cooled to (-5)- (20) C the solution was kept at this temperature for about 8-12 hr, the precipitated solids were filtered off, washed on the filter with cold Toluene (350 mL) to give a wet solid (295.8 g, 83.0%) 110 g of the wet solid were dried at 50C/10 mbar for 2-6 hr to give a wet white solid (94g (LOD= 15-25%) ). The wet white solid (43.75 g) was dissolved at 40-60 C in Ethanol Absolute (215-363 mL 6- 10V), the solution was filtered and returned to the reactor, then the solution was cooled to (-15)- (5) C and was kept at this temperature for about 2-24 hr. The precipitated solids were filtered off, washed with cold Ethanol Absolute (23-35 mL) to give wet solid which was dried at 50 C/10 mbar to constant weight to give cilexetil candesartan (21.5 g, 67 %). At the same time, in my other blogs, there are other synthetic methods of this type of compound, Trityl candesartan, and friends who are interested can also refer to it. Reference:
Patent; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2005/37821; (2005); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 934-22-5, name is 6-Aminobenzimidazole, molecular formula is C7H7N3, 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: C7H7N3

Compound 473: 1 -(1 H-benzo[d]imidazol-6-yl)-5-(2,6-difluorophenyl)-3-hydroxy-4- methyl-1 H-pyrrol-2(5H)-one; 1H-Benzoimidazol-5-ylamine (1 mmol) was dissolved in 5ml_ of dry EtOH and 2,6-difluoro – benzaldehyd (1 mmol) were added. The solution was stirred overnight and after that 2-oxal- propionsaure diethylester (1 mmol) was added and the solution was stirred for 2Oh at 500C. After that the solvent was evaporated and remaining oil was subjected to a flash chromatography device and purified by means of a CHC^/MeOH gradient. The purified carboxylic acid ethyl ester derivative was suspended in 1OmL of a 10% aqueous solution of HCI and kept for 3h at reflux. The resulting precipitate was filtered off and dried.Yield: 0.098g (28 %);1H-NMR 400 MHz, CD3OD11.81 (s, 3H, CH3), 6.17(s, 1 H, CH-N), 6.72 – 6.83 (m, 1 H, aro), 6.93 – 7.08 (m, 1 H, aro) 7.21 -7.37 (m, 1 H, aro), 7.74(m, 2H, benzimid), 8.07 (s, 1 H, benzimid), 9.28 (s, 1 H, benzimid) MS m/z 342.0 (M+H)+, HPLC (254 nm): purity 99 % molecular weight (g/mol): 341.31 Ki: hQC (nM): 29.2

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 934-22-5, its application will become more common.

Reference:
Patent; PROBIODRUG AG; WO2008/55945; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 570-22-9, These common heterocyclic compound, 570-22-9, name is 1H-Imidazole-4,5-dicarboxylic acid, 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: 10 mL ethanol solution of 2.0 mmol metal salt was added into 10 mL ethanol solution of 2.0 mmol 4,5-imidazole dicarboxylic acid. Having blended the mixture under reflux for 1 h, methanol solution of 1.0 mmol NaOH was put into hot mixture drop by drop. After 5 h under reflux, solvent of the solution was removed, precipitate was filtered. The precipitates were washed with methanol 3 times and dried in 105 C. Molecular structures of complexes obtained from the reaction of 4,5-imidazole dicarboxylic acid ligand with metal salts were summarized in Fig. 2.1.

Statistics shows that 1H-Imidazole-4,5-dicarboxylic acid is playing an increasingly important role. we look forward to future research findings about 570-22-9.

Reference:
Article; Erdem, Ozlem; Yildiz, Emel; Inorganica Chimica Acta; vol. 438; (2015); p. 1 – 4;,
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. 53439-88-6, name is 5-Amino-1,3-dimethyl-1H-benzo[d]imidazol-2(3H)-one, A new synthetic method of this compound is introduced below., Formula: C9H11N3O

A mixture of 1.00 g (4.71 mmol) of ethyl (2-cyano-3-ethoxyprop-2-enoyl)carbamate (for preparation see: Senda, Shigeo, Hirota, Kosaku, Notani, Jiyoji; Chemical & Pharmaceutical Bulletin (1972), 20(7), 1380-8) and 835 mg (4.71 mmol) of 5-amino-1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one in 5 ml of acetonitrile and 10 ml of DMF was stirred at reflux temperature overnight. After cooling to RT, the mixture was diluted with 150 ml of diethyl ether and the precipitate was filtered off. The filter residue was stirred with 10 ml of methanol, and the solid was filtered off, washed with a little methanol and ether and dried under high vacuum. This gave 703 mg (45% of theory) of the title compound. LC-MS (Method 1): Rt=0.53 min; m/z=298 (M+H)+. 1H-NMR (400 MHz, DMSO-d6): delta [ppm]=3.30 (br. s, 3H), 3.36 (br. s, 3H), 7.17 (dd, 1H), 7.23-7.28 (m, 1H), 7.34 (d, 1H), 8.77 (s, 1H).

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; Bayer Pharma Aktiengesellschaft; Furstner, Chantal; Ackerstaff, Jens; Straub, Alexander; Meier, Heinrich; Tinel, Hanna; Zimmermann, Katja; Zubov, Dmitry; Schamberger, Jens; (69 pag.)US2016/244415; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 16265-04-6, name is 2-Chloro-1H-imidazole, molecular formula is C3H3ClN2, 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. Quality Control of 2-Chloro-1H-imidazole

B’-1 (2.05g, 20.0 mmol), B’-2 (3.38 g, 20.0mmol), Pd2(dba)3 (0.18g, 0.2mmol), PtBu3 (0.04g, 0.4mmol) and KOtBu (1.44g , 15.0 mmol) were dissolved in 40 ml of toluene, and the mixture was stirred at 80 C for 4 hours. The reaction mixture was cooled to room temperature, and extracted three times with 50 mL of water and 30 mL of diethyl ether. The combined organic layer was dried over MgSO4 and the solvent was evaporated. The resulting residue was purified by silica column method to obtain Intermediate B-1 (3.86 g, yield 82%)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 16265-04-6, its application will become more common.

Reference:
Patent; Choi Don-su; Choi Jin-sol; (70 pag.)KR2019/35043; (2019); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

These common heterocyclic compound, 104619-51-4, name is Di(1H-imidazol-1-yl)methanimine, 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. COA of Formula: C7H7N5

EXAMPLE 36; 3-Cyclopentyl-1-methyl-2-pyridin-2-yl-1H-indole-6-carboxylic acid {1- [6- (5- amino-1,3, 4-oxadiazol-2-yl)-1-methyl-1 H-benzimidazol-2-yl] cyclobutyl} amide; C- (Di-imidazol-1-yl)-methyleneamine (25 mg, 0.16 mmol) was added in a single portion to a solution of compound 35-3 (Example 35) (80 mg, 0.14 mmol) in THF (4 mL). The resulting solution was heated to 70 C for 16 h, after which time a white precipitate was observed. The reaction was then concentrated under reduced pressure, dissolved in 4 mL DMSO and directly purified on a reversed phase Cis, semi-preparative HPLC column (using a solvent gradient from 5% H20 in MeCN to 100% MeCN) to isolate compound 36-1 (compound 1129, Table 1) as a yellow amorphous solid in >95% homogeneity (19 mg, 23% yield). ‘H NMR (400 MHz, DMSO): 5 1.54-1. 67 (m, 2H), 1.79-1. 94 (m, 6H), 1.95-2. 06 (m, 1H), 2.11-2. 23 (m, 1H), 2.74-2. 84 (m, 2H), 3.19-3. 05 (m, 3H), 3.69 (s, 3H), 3.91 (s, 3H), 7.49 (dd, J = 1.8 & 5.7 Hz, 1 H), 7.59-7. 71 (m, 3H), 7.86-7. 92 (m, 2H) 7. 96-8. 01 (m, 1H), 8.06-8. 10 (m, 1H), 8. 10 (s, 1H), 8.78 (d, J = 4.3 Hz, 1H), 9.51 (s, 1H).

The synthetic route of Di(1H-imidazol-1-yl)methanimine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GmbH; BOEHRINGER INGELHEIM PHARMA GmbH & CO KG; WO2005/80388; (2005); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 1179361-84-2, name is Ethyl 1-amino-1H-imidazole-5-carboxylate, molecular formula is C6H9N3O2, 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 Ethyl 1-amino-1H-imidazole-5-carboxylate

Preparation of intermediate II-29; A mixture of intermediate II-30 and NH4CI in 7N NHa/MeOH solution was heated at 90C (sand bath) in a closed vessel for 72h. The reaction was heated at 110C for 24 h. Fresh 7N was added (20 mL) and the reaction was heated at 120C for 5 h. Solvents were evaporated to dryness. The residue was partitioned between EtOAc/water. The organic layer was washed once with water, dried and evaporated to give only 11 mg of residue. The aqueous layer was evaporated to dryness to give 400 mg of a white solid, as a mixture of desired product, intermediate 11-29 and NH4CI salts (yield > 100%) that was used as such in next reaction.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1179361-84-2, its application will become more common.

Reference:
Patent; CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS (CNIO); PASTOR FERNANDEZ, Joaquin; MARTINEZ GONZALEZ, Sonia; ALVAREZ ESCOBAR, Rosa Maria; RODRIGUEZ HERGUETA, Antonio; MARTIN HERNANDO, Jose Ignacio; RAMOS LIMA, Francisco, Javier; WO2011/89400; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 68282-53-1,Some common heterocyclic compound, 68282-53-1, name is 5-Methyl-1H-imidazole-4-carbaldehyde, molecular formula is C5H6N2O, 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.

COMPOUND 12.1.55: N,N-DIETHYL-4-{7-[(4-METHYL-1H-IMIDAZOL-5- YL) METHYL1-6J. 8, 9-TETRAHYDROri31DIOXOLOr4, 5-F] ISOOUINOLIN-6- YL}BENZAMIDE; 4-Methyl-imidazole-5-carboxyaldehyde (76. 4 mg, 0.69 mmol) was added to a solution of INTERMEDIATE 5.1. 15 (122.6 mg, 0.35 mmol) in 1,2-dichloroethane (5 mL) and the reaction mixture stirred at room temperature for 10 min. Sodium triacetoxyborohydride (516 mg, 2.43 mmol) was added followed by N-methyl-2- pyrrolidinone (400 I1L) and the reaction mixture stirred at RT for 18 h. 1 N NaOH (5 mL) was added and the organic solvent removed in vacuo. The residue was extracted with EtOAc (3 x 20 mL) and the organic layer washed with water (20 mL). The organic layer was concentrated in vacuo and the residue purified by flash chromatography on Si02 column (EtOAc: MeOH 95: 5) to afford COMPOUND 12.1. 55 as an oil (35.6 mg, 23%). 1H NMR (500 MHz, CDC13) : 8 1.13 (br s, 3H), 1.25 (br s, 3H), 2.09 (s, 3H), 2.55 (m, 1H), 2. 78 (m, 1H), 3.09 (m, 1H), 3.28 (br s, 2H), 3.34-3. 40 (m, 2H), 3.55 (br s, 2H), 3.59 (d, J 13.5 Hz, 1H), 4. 58 (s, 1H), 5.96 (s, 1H), 6. 21 (d, J 8 Hz, 1H), 6.55 (d, J 8 Hz, 1H), 7.28-7. 32 (m, 4H), 7.36 (s, 1H) ; 13C NMR (125 MHz, CDCl3) : 8 11. 37, 13. 11, 14.42, 22.28, 39.61, 43.64, 45.72, 49.40, 67.41, 101. 30, 106.56, 117. 66,122. 17, 126.56, 129.73, 130.71, 131.73, 133.45, 136.22, 144.81, 145.28, 145.54, 171. 54; (+) LRESIMS m/z 447.20 [M+H] +.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Methyl-1H-imidazole-4-carbaldehyde, its application will become more common.

Reference:
Patent; ASTRAZENECA AB; WO2005/61484; (2005); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem