Category: 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. Formula: C4H5BrN2

Intermediate 3: Step b (1-Methyl-1H-imidazol-5-yl)(thiazol-5-yl)methanone To a solution of 5-bromo-1-methyl-1H-imidazole (1.14 g, 7.11 mmol) in DCM was added ethyl magnesium bromide (2.34 mL, 7.11 mmol; 3 M in diethyl ether) dropwise over a 10 minute period. The resulting pale yellow solution was stirred at room temperature for 15 minutes, cooled in an ice bath to 0 C. and N-methoxy-N-methylthiazole-5-carboxamide (Intermediate 3, step a) (1.02 g, 5.92 mmol) dissolved in DCM (3 mL) was added dropwise. The cold bath was removed and the reaction mixture stirred at room temperature for 48 hours. To the resulting yellow suspension was added water followed by 6 M aqueous HCl to a neutral pH (pH=6-7). The aqueous mixture was extracted with DCM, dried over Na2SO4, filtered and concentrated. Et2O was added and the mixture sonicated. The precipitates were collected by filtration and dried to provide the title compound as a tan solid.

The synthetic route of 1003-21-0 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; US2014/107096; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, 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. HPLC of Formula: C4H5BrN2

5-bromo-1-methyl-1H-imidazole (47.96 g, 297.9 mmol) followed by THF (537 mL) was added to a 3 L four necked flask equipped with an overhead stirrer, nitrogen bubbler and thermocouple. To this room temperature solution was added isopropyl magnesium chloride / lithium chloride complex (246.8 mL, 320.8 mmol, 1.3 M in THF) (addition temperature maintained at 16.6-25 [deg.] C) to give a lean pumice suspension and stir the reaction for 60 min And then cooled to 5.3 in an ice bath. To this mixture was added a solution of N-methoxy-N-methyl-6- (trifluoromethyl) nicotinamide (53.66 g, 229.1 mmol, intermediate 4: step b) in THF (268 mL) 5.3 to 5.6 & lt; 0 & gt; C) to give an orange mixture. After the addition, the reaction was allowed to warm to room temperature over 2 hours. After stirring at room temperature for 18 hours, THF (200 mL) was added and the reaction was stirred for 2 hours. The reaction was then cooled to 4 C with an ice bath, carefully quenched with a 2N HCl aqueous solution at pH = 7, and the quenching temperature reached 12 C. The mixture was diluted with ethyl acetate (500 mL), the phases were separated and the organic layer was washed with brine (2 x 200 mL), dried over sodium sulfate, filtered and the solvent removed. After addition of hot ether, filtration yielded the title compound as a solid.

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

Reference:
Patent; Janssen Pharmaceutica, N.V; Leonardo, Christie.A; Barubay, Kent; Edward, James P.; Kirsten, Kevin D.; Kumar, David A.; Maharupe, Uma; Nishimura, Rachel; Urbanski, Modu; Venkatesan, Hariharan; Wang, Ai Hua; OhLynn, Ronald L.; Woods, Craig R.; Fourier, Anne; Shu, Jia Hu; Cummings, Maxwell D.; (50 pag.)KR2016/70823; (2016); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 1003-21-0,Some common heterocyclic compound, 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, molecular formula is C4H5BrN2, 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 5-bromo-1-methyl-1H-imidazole (25.0 g, 155 mmol; dried over 3 A molecular sieves, then filtered) in DCM (310 mL) was stirred on an ice bath while iPrMgCl (72 mL, 2.01 M solution in THF, 145 mmol) was added rapidly dropwise under argon via pressure-equalizing addition funnel. Residual iPrMgCl was rinsed down with 50 mL THF, and the ice bath was removed and the reaction stirred for 25 minutes. A solution of tert-butyl 4-formylpiperidine-1-carboxylate (27.6 g, 130 mmol) (PharmaCore) in THF (65 mL) was added dropwise over ?5 minutes via pressure-equalizing addition funnel at room temperature. After stirring 1 hour at room temperature, the yellow mixture was quenched with 5 M aqueous NH4Cl (250 mL) in one portion. The organic layer was dried (Na2SO4), filtered, and concentrated to provide the crude title compound as a clear light amber oil.

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-1H-imidazole, its application will become more common.

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

Related Products 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.

Example 14a: 4-((3-(4-(1H-1,2,4-triazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(hydroxy)(1-methyl-1H-imidazol-5-yl)methyl)benzonitrile A solution of isopropylmagnesium chloride-lithium chloride complex in tetrahydrofuran (1.3 M, 0.986 mL, 1 ,28 mmol) was added dropwise to an ice-water cooled, stirring suspension of 5- bronio-1 -methyl- IH- imidazole (241 mg, 1.50 mmol) in dry tetrahydrofuran (6 mL). After 5 minutes, the flask was removed from the cooling bath and the white suspension was stirred at 23 C. After 10 minutes, the Grignard suspension was added to an ice-water cooled, stirring mixture containing 4-(3-(4-( IH- 1 ,2,4-triazol- 1 -yl)benzyl)-4-chloro-2-methoxyquinoline-6- carbonyl)benzonitrile (205 mg, 0.427 mmol, Intermediate 16: step e) and lanthanum(III) chloride bis(lithium chloride) complex (0.6 M solution in tetrahydrofuran, 1.42 mL, 0.854 mmol) in dry tetrahydrofuran (8 mL), After 20 minutes, 1 M aqueous citric acid solution (1 niL) was added. The flask was removed from, the cooling bath and then ethyl acetate (100 mL) was added. Additional 1 M aqueous citric acid solution (-15 mL) was added until the mixture was comprised of two homogeneous layers, at which point saturated aqueous sodium bicarbonate solution was added until the H of the aqueous layer was ~8 by litmus paper test. The layers were separated. The aqueous layer was extracted with ethyl acetate (20 mL). The organic layers were combined and the combined solution was dried over sodium sulfate. The dried solution was filtered. Silica gel (5 g) was added to the filtrate and the mixture was concentrated by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a silica gel column for flash-column chromatography purification. Elution with dichloromethane initially, grading to 50% methanol–dich.lorometh.ane provided the title compound as a w hite solid. H NMR (5001 MHz, CDCI3) delta ppm 8.45 (s, 1H), 8.10 (d . ./ 2.2 Hz, 1 I S). 8.0(S (s, U S). 7.81 (d, ,/ 8.8 Hz, 1H), 7.65 (d, J = 8.5 Hz, 2H), 7.58-7.51 (m, 5H), 7.44-7.38 (m, 3H), 6.41 (d, ,7 = 1.1 Hz, 1H), 4.33 (s, 2H), 4.09 (s, 3H), 3.94 (s, 1H), 3.38 (s, 3H); MS (ESI): mass calcd. C31H24CIN7O2, 561.2; m/z found, 562.1 [M+H]+.4-((3-(4-(l H-l ,2,4-Triazol-l-yl)benzyl)-4-chloro-2-methoxyquinolin-6lH-imidazol-5-yl)methyl)benzonitrile was purified by chiral SFC (Chiralpak AD-H column, 5 mupiiota, 250 mm. 20 mm, mobile phase: 60% C02, 40% methanol) to give two enantiomers. The first eluting enantiomer was Example 14b:3H NMR (500 MHz, CDCI3) delta ppm 8.44 (d, J = 1.0 Hz, 1H), 8.10 (d, J= 2.1 Hz, 1 H), 8.06 (s, 1 H), 7.81 (d, J= 8.7 Hz, 1H), 7.66 (d, J= 8.2 Hz, 2H), 7.58-7.50 (m, 5H), 7.44-7.38 (m, 3H), 6.42 (s, 1H), 4.33 (s, 2H), 4,09 (s, 3H), 4.02-3.81 (br s, 1 H), 3.38 (s, 3H); MS (ESI): mass calcd. C31H24CIN7O2, 561.2; m/z found, 562.3 [M+H]+ and the second eluting enantiomer was Example 14c: H NMR (500 MHz, CDCI3) delta ppm. 8.45 (s, I I I). 8.09 (d, J —— 2.2 Hz, 1 H), 8.06 (s, IH), 7.85 (d, ./ 8.9 Hz, 1H), 7.66 (d, ./ = 8.1 Hz, 21 1).7.58-7.51 (m, 5H), 7.45-7.38 (m, 3H), 6.43 (s, 5 H), 4.33 (s, 2H), 4.09 (s, 3H), 3.38 (s, 3H); MS (ESI): mass calcd. C31H24CIN7O2, 561 .2; m/z found, 562.3 [M+H]+.

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

Adding a certain compound to certain chemical reactions, such as: 1003-21-0, name is 5-Bromo-1-methyl-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 1003-21-0, Product Details of 1003-21-0

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.

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

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.

Example 2Synthesis of [2-(indan-2-ylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-[l-(3- methylimidazol-4-yl)pyrazol-4-yl]methanone.Place [2-(indan-2-ylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-(lH- pyrazol-4-yl)methanone (0.142 g, 0.40 mmoles), 5-bromo-l-methyl-imidazole (89 mg, 0.55 mmoles), cesium carbonate (257 mg, 0.79 mmoles), (1R,2R)- diaminomethylcyclohexane (16 mg, 0.12 mmoles), and copper(I) iodide (7.50 mg, 0.039 mmoles) in a microwave reaction vessel. Add toluene (2 mL) and dimethylformamide (2 mL). The vessel is sealed and purged three times and heated at 110C for 48 hrs. The reaction is allowed to cool to room temperature and is quenched with water (2 mL). Extract three times with ethyl acetate. Dry over sodium sulfate, filter and concentrate under reduced pressure. The residue is purified by reverse phase chromatography to give the title compound (0.078 g, 0.42%). LCMS (m/z): 441.2 (M+l).

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

Reference:
Patent; ELI LILLY AND COMPANY; BLEISCH, Thomas John; DOTI, Robert Anthony; PFEIFER, Lance Allen; NORMAN, Bryan Hurst; WO2014/168824; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application 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.

Ethylmagnesium bromide (3 M in Et2O, 0.0642 mL, 0.193 mmol) was added dropwise to a solution of 5-bromo-1-methyl-1H-imidazole (31.0 mg, 0.193 mmol) in DCM (1 mL) under a nitrogen atmosphere. The mixture was stirred at room temperature for 15 min, then was cooled to 0 C. A solution of (2,4-dichloro-3-phenylquinolin-6-yl)(3-methylisoxazol-5-yl)methanone (49.2 mg, 0.128 mmol, Intermediate 37, step b) in DCM (2 mL) was added via cannula. The mixture was stirred at room temperature for 2 hours. The reaction was quenched by addition of saturated aqueous NH4Cl and was diluted with water. The mixture was extracted three times with EtOAc. The organic phase was dried (Na2SO4), filtered, and concentrated. The crude product was purified by RP-HPLC (10-90% CH3CN-H2O, 0.1% TFA) to afford the title compound. 1H NMR (400 MHz, DMSO-d6) delta 8.99 (br. s., 1H), 8.39 (s, 1H), 8.10-8.25 (m, 2H), 7.83 (d, J=9.05 Hz, 1H), 7.47-7.63 (m, 3H), 7.36-7.47 (m, 2H), 7.27 (br. s., 1H), 6.38 (s, 1H), 3.52 (s, 3H), 2.24 (s, 3H); MS m/e 465.1 [M+H]+.

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; Mirzadegan, Taraneh; Ganamet, Kelly; US2014/107097; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, molecular formula is C4H5BrN2, 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 5-Bromo-1-methyl-1H-imidazole

To a flask containing 5-bromo-1-methyl-1H-imidazole (360 mg, 2.24 mmol) was added THF and the solution was cooled to 0 C. To this clear homogeneous solution was added isopropyl magnesium chloride-LiCl complex (1.3 M, 2.3 mL, 2.98 mmol) which resulted in a white suspension. The reaction mixture was stirred at 0 C. for 30 min, and a THF (2 mL) solution of N-methoxy-N,2,6-trimethylnicotinamide (522 mg, 2.69 mmol, Intermediate 40, step a) was introduced and the mixture was allowed to warm to room temperature for 3 hours and then heated to 50 C. for 20 hours. The contents were cooled to room temperature, poured into a saturated NH4Cl solution and extracted with EtOAc (4×50 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. Flash chromatography on silica gel (25-50% Acetonitrile-DCM increasing gradient to 5% MeOH-DCM) afforded the title compound as a pale yellowish solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1003-21-0, its application will become more common.

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

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

To a flask containing 5-bromo-1-methyl-1H-imidazole (345 mg, 2.14 mmol) was added THF (8 mL) and the solution was cooled to 0 C. To this clear homogeneous solution was added isopropylmagnesium chloride-LiCl complex (1.3 M, 2.0 mL, 2.6 mmol) which resulted in a white suspension. The reaction was stirred at 0 C. for 30 min, then a THF (2 mL) solution of N-methoxy-N,2-dimethylthiazole-4-carboxamide (250 mg, 1.34 mmol, Intermediate 38, step a) was introduced and the mixture became more viscous and was allowed to warm to room temperature. After 3 hours the mixture was quenched with saturated NH4Cl solution and extracted with EtOAc (4×50 mL). The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. Flash chromatography on silica gel (20-40% EtOAc-DCM increasing gradient to 5% MeOH-DCM) provided the title compound as an off-white 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; Mirzadegan, Taraneh; Ganamet, Kelly; US2014/107097; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Related Products of 1003-21-0, These common heterocyclic compound, 1003-21-0, name is 5-Bromo-1-methyl-1H-imidazole, 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 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.

Statistics shows that 5-Bromo-1-methyl-1H-imidazole is playing an increasingly important role. we look forward to future research findings about 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