Category: imidazoles-derivatives

Synthetic Route of 39513-26-3, 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. 39513-26-3 name is 5-Bromo-1,3-dihydrobenzoimidazol-2-one, 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.

To a stirred solution of 5-bromo-lH-benzo[d]imidazol-2(3H)-one104 (930 mg) in a mixture of dioxane (47 ml) and 1 M aqueous sodium carbonate (24 ml) was added 5- quinolylboronic acid105 (906 mg). The reaction mixture was purged three times with Argon before adding 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.358 g) and palladium(II) acetate (0.098 g). The reaction mixture was refluxed for 4 hours. Dioxane was removed by evaporation and ethyl acetate was added. The solid obtained was filtered, dissolved in dichloromethane and washed with water. The organic layer was dried over MgS04, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, eluent: 0 to 5% of methanol in dichloromethane) to afford 5-(2-isopropyl-lH-imidazol-l-yl)-2- nitroaniline (85mg, 27%) as an orange solid. MS (ISP): 247.2 ([M+H]+). The organic layer off and the filter cake was washed with methanol. The filtrate was concentrated in vacuo to 5- quinolin-5-yl-l,3-dihydro-benzoimidazol-2-one as a dark brown solid (949 mg). MS (ISP): 262.2 ([M+H]+).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Bromo-1,3-dihydrobenzoimidazol-2-one, and friends who are interested can also refer to it.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; GOERGLER, Annick; NORCROSS, Roger; DEY, Fabian; KUSZNIR, Eric Andre; (206 pag.)WO2019/43217; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 1615-14-1,Some common heterocyclic compound, 1615-14-1, name is 2-(1H-Imidazol-1-yl)ethanol, molecular formula is C5H8N2O, 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.

Diethyl azodicarboxylate (435 mg, 2.5 mmol) was added dropwise to a suspension of 7-hydroxy-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin4-one (612 mg, 2 mmol), 2-(imidazol-1-yl)ethanol (280 mg, 2.5 mmol), (J. Med. Chem. 1993, 25 4052-4060), and triphenylphosphine (655 mg, 2.5 mmol) in methylene chloride (10 ml) at 5 C. The mixture was stirred for 10 minutes at 5 C. and then 1 hour at ambient temperature. The mixture was poured directly on to a silica column and eluted with methylene chloride/methanol (95/5) to give 7-(2-(imidazol-1-yl)ethoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (640 mg, 80%). 1H NMR Spectrum: (CDCl3) 1.19(s, 9H); 3.98(s, 3H); 4.34(m, 2H); 4.45(m, 2H); 5.94(s, 1H); 7.02(s, 1H); 7.07(s, 1H); 7.11(s, 1H); 7.64(s, 1H); 7.67(s, 1H); 8.17(s, 1H). MS-ESI: 423 [MNa]+

The synthetic route of 1615-14-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Zeneca Limited; US6265411; (2001); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 2620-76-0, These common heterocyclic compound, 2620-76-0, name is 2-(4-Bromophenyl)-1-phenyl-1H-benzoimidazole, 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.

(1-7) Synthesis of Compound (1); Into a 300 ml three-necked flask, 2.0 g (5.0 mmole) of Intermediate 6, 3.9 g (11 mmole) of 2-(4-bromophenyl)-1-phenylbenzimidazole, 0.23 g (0.20 mmole) of tetrakis(triphenylphosphine)palladium(0), 50 ml of 1,2-dimethoxyethane and 15 ml (30 mmole) of a 2 M aqueous solution of sodium carbonate were placed under the stream of argon, and the resultant mixture was heated under the refluxing condition for 8 hours. After the reaction was completed, the organic layer was washed with water and dried with magnesium sulfate, and the solvent was removed by distillation using a rotary evaporator. The obtained crude crystals were washed with 50 ml of toluene and 100 ml of methanol, and 3.4 g of a light yellow powder substance was obtained. The obtained substance was identified to be Compound (1) by the measurement of the field desorption mass spectrum (FD-MS) (the yield: 80percent).

The synthetic route of 2620-76-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Idemitsu Kosan Co., Ltd.; US8058450; (2011); B2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 35203-44-2,Some common heterocyclic compound, 35203-44-2, name is 1-Propyl-1H-imidazole, molecular formula is C6H10N2, 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 100-mL two-neck flask was placed, N-propylimidazole (2.10 g, 18.0 mmol) and 35 mL of toluene were added, and 3-bromopropyldiethoxyphosphine oxide (5.18 g, 20.0 mmol) was added dropwise with heating and stirring.And reacted at 85 °C for 6 h and cooled to room temperature. Pour out the upper toluene,100 mL of deionized water was added to dissolve the product to obtain an aqueous phase. The aqueous phase was washed with an EtOAc_PE=3:1 organic phase (30 mL×4) to separate the aqueous phase II; di(2-ethylhexyl) phosphate (P204). ) (5.80 g, 18.0 mmol) was refluxed under the action of sodium for 24 h. The resulting sodium salt was dissolved in methylene chloride and the separated aqueous phase was stirred at room temperature for 3 h.Add 50 mL of CH2Cl2 and stir to separate the organic phase. The organic phase was washed with deionized water (20 mL×5) and the organic phase was obtained after liquid separation. The organic phase was dried by adding anhydrous Na 2 SO 4 , filtered, and most of the CH 2 Cl 2 was evaporated under reduced pressure and dried in vacuum at 70° C. for 3 h. Yellow sticky liquid product 9.45g (yield 86percent),

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

Reference:
Patent; Ningbo University; Wang Junping; Liang Hongze; Feng Da; Zhao Jieying; Kang Xinchun; Zhang Xiaozhen; Shen Fei; Huang Feilong; (21 pag.)CN104945435; (2018); B;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

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

COMPOUND 12.1. 60: N*N-DIETHYL-4-f6-METHOXY-2-r (5-METHYL-1H- IMIDAZOL-4-YL) METHYLI-7- (NEOPENTYLOXY-1, 2, 3, 4- TETRAHYDROISOOUINOLIN-1-YUBENZAMIDE; To a solution of INTERMEDIATE 7.1. 4 (18 mg, 0.0424 mmol), 4-methyl-1H- imidazole-5-carboxaldehyde (5.8 mg, 0.052 mmol, 1. 2eq) in 1,2-dichloroethane (2 mL) was added sodium triacetoxyborohydride (11.1 mg, 0.052 mmol). The reaction mixture was stirred at room temperature for overnight, then diluted with dichloromethane (5 mL), quenched with saturated aqueous sodium bicarbonate (0.5 mL) and separated. The organic phase was washed with brine (1 x 2 mL), dried (MgSO4) and filtered. To the filtrate ps-scavenger was added, stirred for 2hr and filtered. The filtrate was concentrated and purified by flash chromatography to give compound COMPOUND 12.1. 60 (15 mg, 0.0029 mmol, 68%) as colorless oil. lHNMR (500 MHz, CD2Cl2) : No. 0. 89 (s, 9H), 1.00 (br s, 3H), 1.24 (br s, 3H), 1.90 (s, 3H), 1.99 (s, 2H), 2.45 (m, 1H), 2.68 (m, 1H), 2. 82 (m, 2H), 3.15 (br s, 2H), 3.28 (m, 2H), 3.40 (br s, 2H), 3.70 (s, 3H), 4.45 (s, 1H), 6.10 (br s, 1H), 6.51 (s, 1H), 7.29-7. 33 (m, 4H), 8.18 (s, 1H). (+) LRESIMS m/z 519 [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; ASTRAZENECA AB; WO2005/61484; (2005); 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. 4857-06-1, name is 2-Chloro-1H-benzo[d]imidazole, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 2-Chloro-1H-benzo[d]imidazole

To a solution of 2-Chloro-1- isopropyl-1H-benzoimidazole (167.5 mg, 1.00 mmol) in DMF (4 mL) was added NaH (60% in mineral oil, 36 mg, 1.2 mmol) at 0 oC. After stirring 30 minutes at r.t., 2-Bromo-propane (244 mg, 1.20 mmol) was added dropwise and the reaction mixture was stirred at 37 oC for 12 hours. Then the reaction was quenched by water (30 mL) and extracted with EtOAc (50 mL x 3). The combined organic layer was washed with brine and dried over Na2SO4. The mixture was filtered and the filtrate solvent was removed under reduced pressure. The residue was purified via silica gel column chromatography (Petroleum ether/EtOAc) to give the title compound (105 mg, 53.2% yield) as a white solid. LC-MS: Calculated exact mass = 194.1; Found [M+H]+ =195.2; 197.2.

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:
Patent; KYMERA THERAPEUTICS, INC.; MAINOLFI, Nello; JI, Nan; KLUGE, Arthur F.; (282 pag.)WO2019/140387; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

These common heterocyclic compound, 14741-71-0, name is Ethyl 2-(1H-benzo[d]imidazol-2-yl)acetate, 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: C11H12N2O2

Method A 4-Amino-3-benzimidazol-2-yl-6-(4-methylpiperazinyl)hydroquinolin-2-one Ethyl 2-benzimidazol-2-ylacetate (1.1 eq) and 2-amino-5-(4-methylpiperazinyl)benzenecarbonitrile (1.0 eq) were dissolved in 1,2-dichloroethane, and then SnCl4 (11 eq) was added. The mixture was heated at reflux overnight. Upon cooling, the mixture was concentrated in vacuo. NaOH (3 M) was added to the solid, and the mixture heated at 80 C. for 0.5 hours. The solid was filtered and washed sequentially with H2O, CH2Cl2, and acetone. LC/MS indicated that the product was present in the acetone layer and the solid. These fractions were combined and purified by silica gel chromatography (5-10% MeOH in CH2Cl2 with 1% Et3N) to give the desired product. LC/MS m/z 375.4 (MH+), Rt 1.65 minutes.

The synthetic route of Ethyl 2-(1H-benzo[d]imidazol-2-yl)acetate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Chiron Coporation; US2003/28018; (2003); A1;; ; Patent; Renhowe, Paul A.; Pecchi, Sabina; Machajewski, Timothy D.; Shafer, Cynthia M.; Taylor, Clarke; McCrea JR., William R.; McBride, Christopher; Jazan, Elisa; US2002/107392; (2002); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 57090-88-7, These common heterocyclic compound, 57090-88-7, name is 1H-Imidazole-4-carbonitrile, 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.

To a soluiton of 1H-imidazole-4-carbonitrile (300 mg, 3.2 mmol) in THF (50 mL) was added LiA1H4 (365 mg, 9.6 mmol). After stirred at reflux overnight, the reaction mixture was quenched by H20 (2 mL). And the mixture was dried over anhydrous Na2SO4 and filtered. The filtrate was evaporated in vacuum. The residue was used for next step without further purification.

Statistics shows that 1H-Imidazole-4-carbonitrile is playing an increasingly important role. we look forward to future research findings about 57090-88-7.

Reference:
Patent; SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE; GARDELL, Stephen; PINKERTON, Anthony B.; SERGIENKO, Eduard; SESSIONS, Hampton; (428 pag.)WO2018/132372; (2018); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 71759-89-2,Some common heterocyclic compound, 71759-89-2, name is 5-Iodo-1H-imidazole, molecular formula is C3H3IN2, 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 1. 4-Iodo-l-methyl-lH-imidazole and 5-iodo-l-methyl-lH-imidazole (1205) [00394] Under an atmosphere of nitrogen at 0 C, a solution of 4-iodo-lH-imidazole (5.82 g, 30.00 mmol) in THF (50 mL) was treated with portionwise addition of sodium hydride (60% dispersion in mineral oil, 1.44 g, 36.00 mmol). After stirring for 30 min at 0 C, iodomethane was added (2.8 mL, 45.00 mmol) and the mixture was stirred for 1 h at 0 C. The reaction mixture was poured into water (100 mL) and was extracted with EtOAc (2 x 100 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to afford 6.24 g (90%) of a -3 : 1 mixture of 4-iodo-l-methyl-lH-imidazole and 5- iodo-1 -methyl- lH-imidazole as a light yellow solid. MS (ESI) m/z 209 [M+H]+. Step 2. terf-Butyl 4-(l-methyl-lH-imidazol-4-yl)-3,6-dihydropyridine-l(2H)-carboxylate and terf-butyl 4-(l-methyl-lH-imidazol-5-yl)-3,6-dihydropyridine-l(2H)-carboxylate (1207) [00395] A -3 : 1 mixture of 4-iodo-l -methyl- lH-imidazole and 5-iodo-l-methyl-lH-imidazole (6.24 g, 30.00 mmol), fert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-5,6- dihydropyridine-l(2H)-carboxylate (1 1.1 g, 36.00 mmol), Pd(dppf)Cl2 CH2Cl2 (2.45 g, 3.00 mmol) and sodium carbonate (6.36 g, 60.00 mmol) in water (60 mL) and 1,4-dioxane (300 mL) was stirred under an atmosphere of nitrogen for 3 h at 80 C. After cooling to ambient temperature, the reaction mixture was poured into EtOAc (100 mL) and was washed with water (2 x 100 mL), dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by silica gel chromatography (eluting with a gradient of 1-5% DCM/MeOH) to afford 5 g (57%) of a -3 : 1 mixture of tert-butyl 4-(l-methyl-lH-imidazol-4-yl)- 3,6-dihydropyridine-l(2H)-carboxylate and tert-butyl 4-(l-methyl-lH-imidazol-5-yl)-3,6- dihydropyridine-l(2H)-carboxylate as a yellow oil. MS (ESI) m/z 264 [M+H]+. Step 3. tert-But l 4-(l-methyl-lH-imidazol-4-yl)piperidine-l-carboxylate and tert-butyl 4-(l- methyl-lH-imidazol-5-yl)piperidine-l-carboxylate (1209) [00396] A -3 : 1 mixture of tert-butyl 4-(l-methyl-lH-imidazol-4-yl)-3,6-dihydropyridine- l(2H)-carboxylate and tert-butyl 4-(l-methyl-lH-imidazol-5-yl)-3,6-dihydropyridine-l(2H)- carboxylate (5 g, 19.01 mmol) and palladium on carbon (10 wt. %, 5 g) in MeOH (100 mL) was evacuated and backfilled with hydrogen several times and was then charged with hydrogen. The resulting mixture was stirred for 1 h at ambient temperature before being filtered and concentrated under vacuum, resulting in 1.7 g (34%) of a -3 : 1 mixture of tert-butyl 4-(l-methyl- lH-imidazol-4-yl)piperidine-l-carboxylate and tert-butyl 4-(l-methyl-lH-imidazol-5- yl)piperidine-l-carboxylate as a yellow oil. MS (ESI) m/z 266 [M+H]+.

The synthetic route of 71759-89-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; FORMA THERAPEUTICS, INC.; BUCKMELTER, Alexandre Joseph; IOANNIDIS, Stephanos; FOLLOWS, Bruce; GUSTAFSON, Gary; WANG, Minghua; CARAVELLA, Justin A.; WANG, Zhongguo; FRITZEN, Edward L.; LIN, Jian; (414 pag.)WO2017/87837; (2017); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 7098-07-9, name is 1-Ethyl-1H-imidazole, 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 7098-07-9, Quality Control of 1-Ethyl-1H-imidazole

A mixture of CoCl26H2O (0.1705 g, 0.8 mmol), NH4VO3(0.1404 g, 0.8 mmol), eIM (0.8 mL), and H2O (8 mL) was heated at about 120 °C for 72 h. After the mixture was cooled to room temperature, dark purple crystals were isolated from the mixture. Yield: 62percent (based on NH4VO3); Anal. Calcd. for C30H52Co2N12O14V4(percent): C, 31.96; H, 4.61; N, 14.91. Found: C, 31.71; H, 4.42; N, 14.58.

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

Reference:
Article; Niu, Yan-Hong; Yang, Song; Li, Ji-Kun; Xu, Yan-Qing; Hu, Chang-Wen; Chinese Chemical Letters; vol. 27; 5; (2016); p. 649 – 654;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem