Category: 26663-77-4

Synthetic Route of 26663-77-4,Some common heterocyclic compound, 26663-77-4, name is Methyl benzimidazole-5-carboxylate, molecular formula is C9H8N2O2, 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.

REFERENCE EXAMPLE 8 (+)-4,5,6,7-tetrahydrohenzimidazole-5-carboxylic acid hydrochloride Methyl benzimidazole-5-carboxylate was subjected to catalytic reduction according to the method described in CROATICA CHEMICA ACTA 45, 297-312 (1973), to obtain methyl 4,5,6,7-tetrahydrobenzimidazole-5-carboxylate.

The synthetic route of 26663-77-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Tokyo Tanabe Company Limited; US5677326; (1997); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 26663-77-4, 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. 26663-77-4, name is Methyl benzimidazole-5-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

Step 1: A mixture of compound 1 (520 mg, 3 mol) and 2M NaOH (5 ml) in MeOH (10 ml) and THF (10 ml) was stirred 70C for overnight. TLC was used to monitor the reaction. The mixture was then concentrated to a residue, added water (30mL) and used citric acid to adjust PHto 5-6. Extracted with EA, the organic layer was separated, washed, dried, filtered and concentrated to get compound 4 as yellow solid (320 mg, 67%)

The chemical industry reduces the impact on the environment during synthesis Methyl benzimidazole-5-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ACETYLON PHARMACEUTICALS, INC.; VAN DUZER, John, H.; MAZITSCHEK, Ralph; WO2014/121062; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 26663-77-4, These common heterocyclic compound, 26663-77-4, name is Methyl benzimidazole-5-carboxylate, 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: To a stirred solution of copper(I) acetate (2.4 mg, 0.020 mmol, 0.10 equiv.), benzimidazole 1a (23.6 mg, 0.20 mmol), and TMP iodonium(III) salt 2a (124.8 mg, 0.24 mmol, 1.2 equiv) in toluene (2 mL), triethylamine (56 mL, 0.4 mmol, 2 equiv) was added under a nitrogen atmosphere. The mixture was stirred for 5 min at room temperature, and the resulting solution was then heated to 50 C for 6 h (the reaction progress was monitored by TLC). After cooling to room temperature, the reaction was quenched by adding 5% aqueous ammonia solution (4 mL). The aqueous layer was extracted thrice with 20 mL of dichloromethane and the combined organic extracts were dried with anhydrous sodium sulfate. The organic solvents were then evaporated under reduced pressure, and the residue was purified by flash column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 1/1) to obtain pure N-phenyl benzimidazole 3aa (38.5 mg, 0.198 mmol) in 99% yield

The synthetic route of 26663-77-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Koseki, Daichi; Aoto, Erika; Shoji, Toshitaka; Watanabe, Kazuma; In, Yasuko; Kita, Yasuyuki; Dohi, Toshifumi; Tetrahedron Letters; vol. 60; 18; (2019); p. 1281 – 1286;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 26663-77-4, A common heterocyclic compound, 26663-77-4, name is Methyl benzimidazole-5-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.

3.50 g of methyl 1H-benzimidazole-5-carboxylate hydrochloride and 6.9 ML of triethylamine were suspended in 35 ML of methylene chloride, to which 5.05 g of trityl chloride was added in small portions at 5 to 10C, and this mixture was stirred for one hour at the same temperature.. The reaction mixture was added to a mixture of ethyl acetate and water, and then the organic phase was separated therefrom.. After the resultant organic phase was washed with water and a saturated sodium chloride solution successively, the washed phase was dried over anhydrous sodium sulfate, and the solvent was distilled out under reduced pressure.. The resultant residue was purified by silica gel column chromatography [eluent; hexane:ethyl acetate=3:1] to yield 3.55 g of a mixture of methyl 1-trityl-1H-benzimidazole-5-carboxylate and methyl 3-trityl-3H-benzimidazole-5-carboxylate as white foam. methyl 1-trityl-1H-benzimidazole-5-carboxylate NMR(400MHz,CDCl3) delta value: 3.90(3H,s), 6.49(1H,d,J=8.8Hz), 7.15-7.19(6H,m), 7.31-7.34(9H,m), 7.61(1H,d,J=8.4Hz), 7.97(1H,s), 8.49(1H,s) methyl 3-trityl-3H-benzimidazole-5-carboxylate NMR(400MHz,CDCl3) delta value: 3.75(3H,s), 7.15-7.19(7H,m), 7.31-7.34(9H,m), 7.77(1H,d,J=8.4Hz), 7.87(1H,d,J=8.4Hz), 8.02(1H,s)

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; TOYAMA CHEMICAL CO., LTD.; Hirono, Shuichi; Shiozawa, Shunichi; EP1445249; (2004); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 26663-77-4,Some common heterocyclic compound, 26663-77-4, name is Methyl benzimidazole-5-carboxylate, molecular formula is C9H8N2O2, 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 solution of methyl 1H-benzo[d]imidazole-5-carboxylate (0.90 g, 5.1 mmol) in DMF(20 ml) was added NaH (0.25 g, 6.2 mmol), and the reaction mixture was stirred at room temperature for 30 mm. Then (2-(chloromethoxy)ethyl)trimethylsilane (0.94 g, 5.6 mmol) wasadded and the reaction mixture was stirred at room temperature for 2 hours. When LCMS showed that the reaction completed, the reaction mixture was diluted with EtOAc (100 mL), washed with H20 (100 mL x 2) and brine (100 mL), dried over Na2504 and concentrated under reduced pressure to afford crude product as an oil, which was purified by column chromatography on silica gel (eluted with petroleum ether/EtOAc = 1:1) to afford mixture ofmethyl 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-benzo[d]imidazole-5-carboxylate and methyl 1- ((2-(trimethylsilyl)ethoxy) methyl)- 1 H-benzo [d] imidazole-6-carboxylate as an oil. LC/MS (m/z): 307 (M+H).To a solution of LiA1H4 (0.30 g, 7.8 mmol) in THF (20 ml) was added solution of Step A product (1.2 g, 3.9 mmol) in THF (30 mL) at 0C, the reaction mixture was allowed to warm to room temperature and stirred for 3 hours. When TLC showed that the reaction completed, the reaction mixture was quenched with sat. aq. NH4C1 (50 mL) and the mixture was filteredthrough a pad of celite. The filtrate was extracted with EtOAc (100 mL), washed with H20 (100 mL) and brine (100 mL), dried over Na2504 and concentrated under reduced pressure to afford mixture of (1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-benzo [d] imidazol-5-yl) methanol and (1- ((2-(trimethylsilyl)ethoxy)methyl)- 1 H-benzo[d]imidazol-6-yl)methanol as an oil, which was used in next step without further purification. ?H NMR (CDC13, 400 MHz) oe 8.03 (s, 1H), 8.02(s, 1H), 7.86-7.79 (m, 2H), 7.64 (s, 1H), 7.61-7.55 (m, 1H), 7.43 (d, J= 7.3 Hz, 1H), 7.36 (d, J=8.4 Hz, 1H), 5.59 (s, 4H), 4.90 (s, 2H), 4.87 (s, 2H), 3.59-3.53 (m, 4H), 0.99-0.91 (m, 4H), 0.00 (s, 9H).To a solution of Step B product (0.3 g, 1.1 mmol) in DCM(10 ml) was added SOC12 (0.8 ml, 10.8 mmol) dropwise at 0C, then the reaction mixture was stirred at room temperature for 3 hours. When TLC showed that the reaction completed, the reaction mixture was diluted with DCM (50 mL), washed with sat. aq. NaHCO3 (50 mL) and brine (50 mL), dried over Na2SO4 and concentrated under reduced pressure to afford a mixture of 5-(chloromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)- 1 H-benzo[d] imidazole and 6-(chloromethyl)- 1 -((2- (trimethylsilyl) ethoxy)methyl)-1H-benzo[d]imidazole as an oil, which was used in next step without further purification. LC/MS (m/z): 297 (M+H).To a solution of Intermediate 2 (0.20 g, 0.65 mmol), Step C product (0.29 g, 0.97 mmol) in acetone (4 ml) and DMF (2 ml) was added K2C03(0.27 g, 1.9 mmol). The reaction mixture was then heated to 60 C and stirred for 6 hours. When LCMS showed that the reaction completed, the reaction mixture was diluted with EtOAc (1 OOmL), washed with H20 (100 mL)and brine (100 mL), dried over Na2504 and concentrated under reduced pressure to afford crude product as an oil, which was purified by column chromatography on silica gel (eluted with Petroleum ether/EtOAc = 1:1) to afford a mixture of tert-butyl 2-(4-hydroxy-2-oxo-1-((1-((2- (trimethylsilyl)ethoxy)methyl)- 1 H-benzo[d]imidazol-5 -yl)methyl)- 1,2,5 ,7-tetrahydrofuro [3,4- b]pyridine -3 -carboxamido)acetate and tert-butyl 2-(4-hydroxy-2-oxo- 1 -((1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-benzo[d]imidazol-6-yl) methyl)- 1,2,5,7- tetrahydrofuro [3,4- b]pyridine-3-carboxamido)acetate as a solid. LC/MS (m/z):To a solution of HC1 in dioxane (4M, 20 mL) was added Step D product (140 mg, 0.25 mmol), followed by H20 (5 mL), then the reaction mixture was heated to 90 C and stirred for 4 hours. When LCMS showed that the reaction completed, the reaction mixture was concentrated under reduced pressure to afford crude product as a solid. The crude product was triturated withMTBE (10 mL), and the title compound was collected by suction as a powder. ?H NMR(DMSO-d6, 400 MHz) oe 10.24 (t, J= 4.8 Hz, 1H), 9.48 (s, 1H), 7.80 (d, J= 8.4 Hz, 1H), 7.67 (s,1H), 7.44 (d, J= 8.4 Hz, 1H), 5.24 (br s, 2H), 5.02 (br s, 2H), 4.93 (br s, 2H), 4.06 (d, J= 4.9 Hz,2H). LC/MS (m/z): 385 (M+H). Human HIF-PHD2 IC50: 11.8 nM. 571 (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 Methyl benzimidazole-5-carboxylate, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MSD R&D (CHINA) CO., LTD.; CAI, Jiaqiang; CRESPO, Alejandro; DU, Xiaoxing; DUBOIS, Byron Gabriel; LIU, Ping; LIU, Rongqiang; QUAN, Weiguo; SINZ, Christopher; WANG, Liping; (61 pag.)WO2016/49100; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 26663-77-4, name is Methyl benzimidazole-5-carboxylate, molecular formula is C9H8N2O2, 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. SDS of cas: 26663-77-4

Methyl lH-benzo[d]imidazole-5-carboxylaie (528 mg, 3 mrnol) in lOmL of DMF was added NaH (160 mg, 6 mmol) at 0C under 2, then the mixture was stirred at (TC for 30 min, then a solution of tert-butyl 4′-(bromomethyl)biphenyl- 2-carboxylate (1.09 g, 3.15 mmol) in DMF (5 mL) was added dropwise at 0C to the reaction mixture, then the mixture was stirred at RTovernight. The mixture was poured into 50 mL of water. The mixtitre was extracted with EtOAc (30 ml_x3) and washed with water (20 mL) and brine (20mL), dried over Na2S04, filtered, and concentrated. The crude product was purified with Combiflash (hexane/EtOAc = 2/1, silica gel) to obtain the titled compound 1. ? NMR (CHLOROFORM-d) delta 8.57 (s, 1H), 8.13 (s, 3H), 7.98 – 8.06 (m, 5H), 7.75 – 7.82 (m, 2H), 7.46 – 7.53 (m, 2H), 7.37 – 7.44 (m, 4H), 7.22 – 7.35 (m, 14H), 5.49 (s, 2H), 5.46 (s, 3H), 3.96 (s, M l ). 3.95 (s, 3H), 1.19 (d, J – 9.7 Hz, 22H); Step B: l -((2′-(tert-butoxycarbonyl)-[l , i ‘~biphenyl]~4-yl)raetliyl)- lH- benzo[d]imidazole-5-carboxy1ic acid, 1 -((2’-(tert-butoxycarbonyl)- [ 1 , Gamma- biphenyl]-4-yl)methyl)- lH-benzo[d]imidazole-6-carboxylic acid The mixture 1 (from Step A) (300 mg, 0.68 mmol) and LiOH (83 mg, 2.04 mmol) in methanol (5 mL) and H?0 (2 mL) was stirred at RT for 18 h. Methanol was removed under the reduced pressure, then PH was adjusted to 6 with IN HCl. A gradual formation of precipitate was observed and filtered. The filter cake was washed by water (10 mL). The residue was separated and purified with Prep-TLC (PE/EtOAc = 112, silica gel) to give the titled compound 2 and 3. 2 ? NMR (CHLOROFORM-d) : 8.26 (s, 2H), 7.75 7.84 (m, 1H), 7.47 ¡¤ 7.54 (m, l H), 7.38 – 7.44 (m, 1 H), 7.29 – 7.36 (m, 5H), 5.52 (s, 2H), 1 .19 (s, 9H) 3 T NMR (CHLOROFORM-d) delta: 8.76 (s, 1H), 8.31 fs, 1H), 7.77 – 7.85 (m, 1H), 7.38 – 7.54 (m, 4H), 7.33 (t, J = 8.2 Hz, 4H), 5.49 (s, 2H), 1.21 (s, 9H)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 26663-77-4, its application will become more common.

Reference:
Patent; RIPKA, Amy S.; SAUNDERS, Jeffrey O.; KAMENECKA, Theodore Mark; GRIFFIN, Patrick R.; WO2013/78240; (2013); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

A common compound: 26663-77-4, name is Methyl benzimidazole-5-carboxylate, 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. 26663-77-4

tert-butyl-2-chloro-4-fluorobenzoate (200 mg, 0.867 mmol), methyl lH-benzimidazole-5- carboxylate (214 mg, 1.214 mmol) and potassium carbonate (359 mg, 2.60 mmol) in dry acetonitrile (12 mL) was stirred at 85C for 6 h. The reaction mixture was cooled to RT and the solid was filtered and washed with EtOAc. The filtrate was concentrated and purified by flash chromatography (ISCO CombiFlash system, 80g Silica gel column, 0-60% EtOAc in hexane as as eluting solvent) to afford the product as a mixture of two regioisomers. Further separation of this mixture of products by SFC technique on chiral AD-H column and using 55% MeOH/C02 as mobile phase yielded compound 18A-a, methyl l-(4-(tert-butoxycarbonyl)-3-chlorophenyl)- lH-benzo[d]imidazole-6-carboxylate, and compound 18A-b, methyl l-(4-(tert-butoxycarbonyl)- 3- chlorophenyl)-lH-benzo[d]imidazole-5-carboxylate. For compound 18A-a: methyl 1 -(4-(tert-butoxycarbonvD-3 -chlorophenvD- 1 H- benzo[dlimidazole-6-carboxylate (M+H) calc. = 387.10; found = 387.15. 1H NMR (500 MHz, CD3OD): delta 8.70 (s, br, 1 H); 8.30 (s, br, 1 H); 8.08 (dd, J = 1.5 Hz, J = 8.5 Hz, 1 H); 8.01 (d, J = 8.5 Hz,l H); 7.89 (d, J = 2.5 Hz,l H); 7.86 (d, J = 8.5 Hz, 1 H); 7.74 (dd, J = 2.0 Hz, J = 8.5 Hz, 1 H); 3.95 (s, 3H); 1.66 (s, 9H) For compound 18A-b: methyl 1 -(4-(tert-butoxycarbonyl)-3 -chlorophenyD- 1 H- benzo[dlimidazole-5-carboxylate (M+H) calc. = 387.10; found = 387.15. 1H NMR (500 MHz, CD3OD): delta 8.56 (s, br, 1 H); 8.47 (s, br, 1 H); 8.12 (dd, J = 1.5 Hz, J = 8.5 Hz, 1 H); 8.10 (d, J = 8.5 Hz,l H); 7.89 (d, J = 2.0 Hz,l H); 7.76 (d, J = 8.5 Hz, 1 H); 7.73 (dd, J = 2.0 Hz, J = 8.5 Hz, 1 H); 3.97 (s, 3H); 1.65 (s, 9H) Additional NMR studies (NOE) confirmed the structure assignments of the two products.

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, 26663-77-4, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MOCHIDA PHARMACEUTICAL CO., LTD.; ZHANG, Ting; CHEN, Yi-Heng; GUO, Liangqin; HRUZA, Alan; JIAN, Tianying; LI, Bing; MENG, Dongfang; PARKER, Dann, L., Jr.; SHERER, Edward, C.; WOOD, Harold, B.; SAKURADA, Isao; (130 pag.)WO2016/94260; (2016); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem