Category: 1003-21-0

Wang, Zhen; Zhang, Yali; Pinkas, Daniel M.; Fox, Alice E.; Luo, Jinfeng; Huang, Huocong; Cui, Shengyang; Xiang, Qiuping; Xu, Tingting; Xun, Qiuju; Zhu, Dongsheng; Tu, Zhengchao; Ren, Xiaomei; Brekken, Rolf A.; Bullock, Alex N.; Liang, Guang; Ding, Ke; Lu, Xiaoyun published the artcile< Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2-a]pyrazin-3-ylethynyl)-4-isopropyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2>, Safety of 5-Bromo-1-methyl-1H-imidazole, the main research area is design synthesis heterocycloalkynylbenzimide dual inhibitor Discoidin domain receptor; antiinflammatory drug discovery human pharmacokinetic mol modeling.

Discoidin-domain receptors 1 and 2 (DDR1 and DDR2) are new potential targets for anti-inflammatory-drug discovery. A series of heterocycloalkynylbenzimides were designed and optimized to coinhibit DDR1 and DDR2. One of the most promising compounds, I, tightly bound to DDR1 and DDR2 proteins with Kd values of 7.9 and 8.0 nM; potently inhibited the kinases with IC50 values of 9.4 and 20.4 nM, resp.; and was significantly less potent for a panel of 403 wild-type kinases at 1.0 μM. DDR1- and DDR2-kinase inhibition by I was validated by Western-blotting anal. in primary human lung fibroblasts. The compound also dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin 6 (IL-6) release in vitro and exhibited promising in vivo anti-inflammatory effects in an LPS-induced-acute-lung-injury (ALI) mouse model. Compound I may serve as a lead compound for new anti-inflammatory drug discovery.

Journal of Medicinal Chemistry published new progress about Acute toxicity. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Safety of 5-Bromo-1-methyl-1H-imidazole.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 1003-21-0, A common heterocyclic compound, 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, molecular formula is C4H5BrN2, 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 solution of 5-bromo-1-methyl-imidazole (18.8 g, 117 mmol) in dichloromethane (50 mL) was added dropwise ethylmagnesium bromide (3 M in Et2O, 38.9 mL, 117 mmol). After stirring at room temperature for 30 min, the reaction mixture was cooled down to 0C with an ice-brine bath and N-methoxy-N-methylthiophene-3-carboxamide (20.0 g, 117 mmol) was added dropwise. The mixture was stirred for 5.5h at room temperature. The mixture was worked-up by addition of water (400 mL), then acidified with aq. HCI (1 M) until pH = 7. After extraction with dichloromethane (3 x 100 mL), the organic layers were washed with water (2 x 100 mL) then dried over MgSO4 and concentrated in vacuo. Purification of the residue on silica gel afforded (1-methyl-1H-imidazol-5-yl)(2-thienyl)methanone [10.2 g, yield 36% ; HPLC/MS : m/z = 193 (M+H) ; logP(HcooH) = 0.52].

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 CROPSCIENCE SA; WO2009/130193; (2009); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 1003-21-0, 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 1003-21-0 as follows.

lntermediate 1: step b (1-Methyl-lH-imidazol-5-yl)(tetrahydro-2H-pyran-4-yl)methanone A clear colorless solution of 5-bromo-l-methyl-lH-imidazole (1.12 g, 6.93 mmol) in THF (10 mL) was placed in an ice bath and ethylmagnesium bromide (3.0 M in Et20, 2.31 mL, 6.93 mmol) was added via syringe. The reaction mixture was stirred for 20 minutes at room temperature. N-Methoxy~N-methyltetrahydro-2H~pyran-4~ca.rboxamide (1.0 g, 5.8 mmol. Intermediate 1 : step a. Procedure A) was added neat by syringe (using 1 mL THF rinse to quantitate transfer), and the resulting white suspension was stirred at room temperature for 2 days. The mixture was diluted with saturated aqueous NH4C1 followed by water, then was extracted with EtOAc (3 x). The organic phase was dried (Na2S04), filtered, and concentrated to dryness. The crude product was purified by flash column chromatography two times (1 -4% MeOH-DCM first column; 40-60% CH CN-DCM second column) to provide the title compound as a white crystalline solid.

According to the analysis of related databases, 1003-21-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; LEONARD, Kristi A.; BARBAY, Kent; EDWARDS, James P.; KREUTTER, Kevin D.; KUMMER, David A.; MAHAROOF, Umar; NISHIMURA, Rachel; URBANSKI, Maud; VENKATESAN, Hariharan; WANG, Aihua; WOLIN, Ronald L.; WOODS, Craig R.; FOURIE, Anne; XUE, Xiaohua; CUMMINGS, Maxwell D.; JONES, William Moore; GOLDBERG, Steven; WO2015/57205; (2015); 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. 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 5-Bromo-1-methyl-1H-imidazole

General procedure: To a solution 5-bromo-1-methyl-(1H)-imidazole (180mg, 1.13 mmol) in THF (10 mL) HMPA (Hexamethylphosphoramide)was added (130 mg, 0.75 mmol) followed by t-BuLi (170 mg, 2.6 mmol) at -78oC, the resulted mixture wasallowed to stir at rt for 1 h. Then it was cooled back to -78oCand amidosulphone 4a-4j (0.75 mmol) was added in THF (5mL) slowly. The reaction mixture was slowly allowed to stirat rt for 2 h. Then, the reaction mixture was quenched withNH4Cl and extracted into EtOAc. The combined organiclayers were dried over Na2SO4 and distilled in vacuum to getcrude compounds 5a-5j and were purified by column chromatography using 5 % MeOH in DCM to get the final compounds5a-5j with 59-65 % yield.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 1003-21-0.

Reference:
Article; Thripuram, Vijaya Durga; Bollikolla, Hari Babu; Mule, Siva Nagi Reddy; Battula, Sailaja Kumari; Ala, Vasu Babu; Letters in Organic Chemistry; vol. 15; 7; (2018); p. 569 – 574;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 1003-21-0, A common heterocyclic compound, 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, molecular formula is C4H5BrN2, 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.

Ethylmagnesium bromide (3 M in Et2O, 1.04 mL, 3.11 mmol) was added dropwise to a solution of 5-bromo-1-methyl-1H-imidazole (500 mg, 3.11 mmol) in DCM (6 mL) under a nitrogen atmosphere. The mixture was stirred at room temperature 15 min, then was cooled in an ice bath prior to addition of N-methoxy-N-methylpyridazine-4-carboxamide (419 mg, 2.51 mmol, Intermediate 29, step a). The resulting suspension was stirred at room temperature for 2 hours. The reaction was quenched by addition of saturated aqueous NH4Cl, diluted with water, and extracted three times with EtOAc. The aqueous phase was saturated with NaCl and back-extracted with DCM (three times). The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, gradient 30-100% CH3CN-DCM, followed by isocratic 5% MeOH-acetone), affording title compound contaminated with 1-methyl-1H-imidazole, the mixture of which was used in the next reaction without further purification.

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; Janssen Pharmaceutica NV; Leonard, Kristi A.; Barbay, Kent; Edwards, James P.; Kreutter, Kevin D.; Kummer, David A.; Maharoof, Umar; Nishimura, Rachel; Urbanski, Maud; Venkatesan, Hariharan; Wang, Aihua; Wolin, Ronald L.; Woods, Craig R.; Fourie, Anne; Xue, Xiaohua; Mirzadegan, Taraneh; Ganamet, Kelly; US2014/107097; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 1003-21-0, 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. 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Example 88a: (4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)(1-methyl-1H-imidazol-5-yl)methanol To a flask containing 5-bromo-l -methyl- lH-imidazole (650 mg, 4.04 mmol) was added THF (10 mL) and the clear homogeneous solution was stirred at room temperature as z’PrMgCl (2 M in diethylether, 2 mL, 4 mmol) was added. A whitish suspension resulted. The suspension was stirred at room temperature for 30 minutes, then a solution of 4-chloro-2-methoxy-3-(4- (trifluoiOmefhyl)benzyr)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanone (660 mg, 1.36 mmol, Intermediate 81 : step b) in THF (5 mL) containing LaCl3-LiCl complex (0.5 M solution THF, 5 mL, 2.5 mmol) was added to the reaction mixture. The reaction mixture was stirred overnight at 35 C. After 14 hours, the reaction mixture was quenched with saturated aqueous NH4C1 solution. The aqueous portion was extracted with EtOAc (3 x 40 mL) and the combined organics were washed with brine and dried over MgS04. The brine portion was back-extracted with DCM (3 x 40 mL) and dried over MgS04. The organics were filtered and concentrated to dryness to afford a tan oil. The residue was purified by FCC (2% MeOH-DCM increasing to 10% MeOH) to provide the title compound as an off white solid.lH NMR (500 MHz, CDCI3) delta 8.13 (d, J = 2.0 Hz, 1H), 7.76 (d, J = 8.7 Hz, 1H), 7.50 (d, J = 8.2 Hz, 2H), 7.44 – 7.35 (m, 4H), 7.31 (d, J= 1 1.4 Hz, 1H), 7.05 (d, J= 8.0 Hz, 1H), 6.90 (d, J = 8.0 Hz, 1H), 6.19 (s, 1H), 4.67 (s, 1H), 4.32 (s, 2H), 4.07 (s, 3H), 3.46 (s, 3H), 2.52 (s, 3H), 2.45 – 2.33 (m, 3H); MS (ESI): mass calcd. Chemical Formula: C30H2CIF3N4O?, Exact Mass: 566.2, m/z found 567.1 [M+H]”.(4~Chk>ro~2~niethoxy~3-(4-(irifluQmethyl- lH-im.idazol-5-yl)methanol was purified by chiral SFC (Stationary phase: CHIRALPAK AD-H 5 muetaiota 250 x 20 mm, Mobile phase: 75% C02, 25% EtOH), to give two enantiomers. The first eluting enantiomer was Example 88b and the second eluting enantiomer was Example 88c.

The synthetic route of 5-Bromo-1-methyl-1H-imidazole has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; LEONARD, Kristi A.; BARBAY, Kent; EDWARDS, James P.; KREUTTER, Kevin D.; KUMMER, David A.; MAHAROOF, Umar; NISHIMURA, Rachel; URBANSKI, Maud; VENKATESAN, Hariharan; WANG, Aihua; WOLIN, Ronald L.; WOODS, Craig R.; FOURIE, Anne; XUE, Xiaohua; CUMMINGS, Maxwell D.; JONES, William Moore; GOLDBERG, Steven; WO2015/57205; (2015); A1;,
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 1003-21-0 as follows. SDS of cas: 1003-21-0

5-Bromo-1-methyl-1H-imidazole (6.66 g, 41.4 mmol) was added to a round bottom flask followed by tetrahydrofuran (150 mL) under an N2 atmosphere. The contents were cooled to 0 C. in an ice water bath. EtMgBr (3.0 M solution in THF, 13.3 mL, 39.8 mmol) was added slowly via syringe over approximately 5 minutes, then the ice bath was removed and the contents allowed to warm and stirred at room temperature for approximately 30 minutes. The vessel was then re-cooled to 0 C. and a solution of N-methoxy-N-methylpyrimidine-2-carboxamide (3.09 g, 15.9 mmol, Intermediate 66: step a) in THF (20 mL) was cannulated into the reaction vessel. The contents were allowed to stir at 0 C., then slowly warmed to room temperature, then heated to 40 C. in an oil bath for approximately 36 hours. The contents were then cooled to 0 C., quenched with a saturated aqueous NH4Cl solution, diluted with ethyl acetate and transferred to a separatory funnel. The aqueous layer was separated, extracted twice with EtOAc, then the combined organic phases were dried over MgSO4, filtered, then distilled under reduced pressure to yield an amber oil. The crude product was purified by flash column chromatography (silica gel, 0-10% DCM/(10% of a 2 M NH3 MeOH in DCM)) to provide the title compound.

According to the analysis of related databases, 1003-21-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Janssen Pharmaceutica NV; Leonard, Kristi A.; Barbay, Kent; Edwards, James P.; Kreutter, Kevin D.; Kummer, David A.; Maharoof, Umar; Nishimura, Rachel; Urbanski, Maud; Venkatesan, Hariharan; Wang, Aihua; Wolin, Ronald L.; Woods, Craig R.; Fourie, Anne; Xue, Xiaohua; Cummings, Maxwell D.; Jones, William Moore; Goldberg, Steven; US2015/105366; (2015); 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. 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, A new synthetic method of this compound is introduced below., Computed Properties of C4H5BrN2

Example No. 18: Preparation of Compound No. 18[0306] A solution of 2,8-dimethyl-2,3,4,5-tetrahydro- lH-pyrido[4,3-b]indole (0.4 g, 2 mmol), 5-bromo-l-methyl-lH-imidazole (0.644 g, 4 mmol), K3P04 (0.848 g, 4 mmol), Cul (38 mg, 0.2 mmol) and L-Proline (46 mg, 0.39 mmol) in dry DMF (6 mL) was stirred at 150 C for 16h. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford crude material, which was purified by reverse phase HPLC to yield 2,8-dimethyl-5-(3-methyl-3H- imidazol-4-yl)-2,3,4,5-tetrahydro-lH-pyrido[4,3-b]indole (15 mg). 1H NMR (HC1 salt, CD3OD) delta (ppm): 9.20 (s, IH), 8.0 (s, IH), 7.40 (s, IH), 7.20 (d, IH), 7.10 (d, IH), 4.76 (d, IH), 4.40 (d, . n . m, H , . , H , . s, H , . m, z s, 3H).

The synthetic route of 1003-21-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MEDIVATION TECHNOLOGIES, INC.; PROTTER, Andrew, Asher; CHAKRAVARTY, Sarvajit; WO2012/112962; (2012); 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. 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, A new synthetic method of this compound is introduced below., SDS of cas: 1003-21-0

Isopropylmagnesium chloride lithium chloride complex (1.3 M in tetrahydrofuran, 2.0 mL, 2.60 mmol) was added to an ice-water cooled solution of 5-bromo-1-methyl-1H-imidazole (444 mg, 2.76 mmol) in tetrahydrofuran (12 mL). The resulting white suspension was stirred for 5 minutes then the cooling bath was removed. After 10 minutes, the suspension was added dropwise by syringe to an ice-water cooled mixture of (3-(4-(1H-1,2,4-triazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(4-chlorophenyl)methanone (772 mg, 1.59 mmol, Intermediate 45, step e) and lanthanum(III) chloride bis(lithium chloride) complex solution (0.6 M in tetrahydrofuran, 5.25 mL, 3.16 mmol) in tetrahydrofuran (15 mL). After 20 minutes, saturated aqueous ammonium chloride solution was added (2 mL) then the cooling bath was removed. The mixture was diluted with water (25 mL) and ethyl acetate (50 mL). The layers were separated. The aqueous layer was extracted with ethyl acetate (25 mL). The organic layers were combined and the combined solution was dried with sodium sulfate. The dried solution was filtered and the filtrate was absorbed onto 6 g of silica gel for dry-load flash-column chromatography on silica gel eluting with 100% dichloromethane initially for 5 minutes, grading to 7% methanol-dichloromethane over 30 minutes to afford the titled compound as a white solid. 1H NMR (400 MHz, CDCl3) delta ppm 8.43 (s, 1H), 8.12 (d, J=2.1 Hz, 1H), 8.06 (s, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.58-7.50 (m, 3H), 7.41 (d, J=8.5 Hz, 2H), 7.36 (d, J=1.1 Hz, 1H), 7.31 (s, 4H), 6.38 (d, J=1.1 Hz, 1H), 4.33 (s, 2H), 4.12 (s, 1H), 4.08 (s, 3H), 3.38 (s, 3H); MS m/e 571.1 [M+H]+. (3-(4-(iH-i,2,4-triazol-i-yl)ben- zyl)-4-chloro-2-methoxyquinolin-6-yl)(4-chlorophenyl)(i – methyl-iH-imidazol-5-yl)methanol was purified by HPEC (Chiralpak IA column, 50 mmx2SO mm, ethanol with 0.2% triethylamine as eluent, 30 mE/minute, 254 nm wavelength) to give two enantiomers. The first eluting enantiomer was Example 648: ?H NMR (400 MHz, CDC13) oe ppm 8.43 (s, iH), 8.12 (d, J=2.i Hz, iH), 8.06 (s, iH), 7.78 (d, J=8.7 Hz, iH), 7.56-7.50 (m, 3H), 7.41 (d, J=8.5 Hz, 2H), 7.36 (d, J=i .1 Hz, iH), 7.31 (s, 4H), 6.38 (d, J=i.i Hz, iH), 4.33 (s, 2H), 4.08 (s, 3H), 3.38 (s, 3H); MS mle 571.1 [M+H]+ and the second eluting enantiomer was Example 64C: ?H NMR (400 MHz, CDC13) oeppm8.43 (s, iH), 8.12 (d, J=2.i Hz, iH), 8.06 (s, iH), 7.78 (d, J=8.7 Hz, iH), 7.58-7.49 (m, 3H), 7.41 (d, J=8.6 Hz, 2H), 7.35 (s, iH), 7.31 (s, 4H), 6.38 (s, iH), 4.33 (s, 2H), 4.21 (s, iH), 4.08 (s, 3H), 3.38 (s, 3H); MS mle 571.1 [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; Janssen Pharmaceutica NV; Leonard, Kristi A.; Barbay, Kent; Edwards, James P.; Kreutter, Kevin D.; Kummer, David A.; Maharoof, Umar; Nishimura, Rachel; Urbanski, Maud; Venkatesan, Hariharan; Wang, Aihua; Wolin, Ronald L.; Woods, Craig R.; Pierce, Joan; Goldberg, Steven; Fourie, Anne; Xue, Xiaohua; US2014/107094; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 1003-21-0, A common heterocyclic compound, 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, molecular formula is C4H5BrN2, 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.

Ethyl magnesium bromide (3.0 M in diethyl ether, 21.5 mL, 64.4 mmol) was added via syringe over a few minutes to a clear colorless solution of 5-bromo-1-methyl-1H-imidazole (10.4 g, 64.4 mmol) in THF (100 mL) under a nitrogen atmosphere in an ice bath. A white precipitate formed during the addition. The mixture was removed from the ice bath and was stirred for 20 minutes, then was again cooled in an ice bath before addition of 4-chloro-N-methoxy-N-methylbenzamide (10.7 g, 53.6 mmol, Intermediate 1: step a). The resulting white suspension was stirred overnight at room temperature. The reaction was quenched by addition of saturated aqueous NH4Cl and diluted with water. The mixture was partially concentrated to remove THF and was diluted with DCM. The mixture was acidified to pH 1 with 1 N aqueous HCl, then neutralized with saturated aqueous NaHCO3. The phases were separated and the aqueous phase was further extracted with DCM. The organic extracts were washed with water, then were dried (Na2SO4), filtered, and concentrated, affording a white solid. The crude product was triturated with a mixture of EtOAc:heptanes (1:1, 150 mL). The precipitated solid was collected by vacuum filtration, washing with heptanes, to afford the title compound.

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; Janssen Pharmaceutica NV; Leonard, Kristi A.; Barbay, Kent; Edwards, James P.; Kreutter, Kevin D.; Kummer, David A.; Maharoof, Umar; Nishimura, Rachel; Urbanski, Maud; Venkatesan, Hariharan; Wang, Aihua; Wolin, Ronald L.; Woods, Craig R.; Pierce, Joan; Goldberg, Steven; Fourie, Anne; Xue, Xiaohua; US2014/107094; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem