Tag: M.W=100-200

Adding a certain compound to certain chemical reactions, such as: 71759-89-2, name is 5-Iodo-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 71759-89-2, Computed Properties of C3H3IN2

General procedure: Method A: In a20 mL microwave Biotage tube, a mixture of 4-iodo-1H-imidazole(1a) (0.194 g, 1.0 mmol), a boronic acid 2(2.0 mmol), CsF (0.456 g,3.0 mmol), PdCl2(dppf)(0.041 g, 0.05 mmol) and BnEt3NCl(0.011 g, 0.05 mmol) in toluene(7 mL) and water (7 mL)was purged with argon andheated under microwaveirradiation. When the reaction was complete, the mixture was cooled toroom temperature and concentrated under reduced pressure. The residue waspurified by flash chromatography on silica gel to provide compounds 3a-3i and 3k-3o in yields ranging from 40 to 91%. Time and temperaturereactions were collected in Table 1.

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

Reference:
Article; Vichier-Guerre, Sophie; Dugue, Laurence; Pochet, Sylvie; Tetrahedron Letters; vol. 55; 46; (2014); p. 6347 – 6350;,
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. 492-98-8, name is 1H,1’H-2,2′-Biimidazole, A new synthetic method of this compound is introduced below., Formula: C6H6N4

Synthetic example 10:1 , 1 ‘-bis(6-methyl-9-p-tolyl-9H-carbazol-3-y.)-1 H, 1 ,H-2,2i-biimidazole10A mixture of 1W, W-2,2*-biimidazole (890 mg, 6.6 mmol), 3-bromo-6-methyl-9-p-tolyl- 9H-carbazole (6.49 g, 18.6 mmol) and Cs2C03 (7.55 g, 23.2 mmol) in D F (80 mL) was degassed (N2 bubbling, 15 min). Cu20 (380 mg, 2.7 mmol) was added and the mixture was heated (140 C, 96h). The mixture was allowed to cool to room temperature and filtered through Celite washing with CH2CI2. The combined filtrate and washings were concentrated. The mixture was diluted with CH2CI2 and H2O and the organic phase was separated. The aqueous phase was re-extracted (CH2CI2) and the combined organics were washed (saturated aqueous NaCI), dried (MgS04), filtered and concentrated to give a solid residue. The residue was purified by flash chromatography (EtOAc CH2CI2/ eOH 39:60:1 then 37:60:3 then 35:60:5) to give l.r-bisie-methyl-g-p-tolyl-gH-carbazol-S-y -IH.rH^^’-biimidazole (1.42 g, 32%) as a colourless solid. A portion of this material was further purified firstly, by recrystallisation (CH2CI2/toluene/petrol) and then by distillation (sublimation apparatus 270 C, 1CT6 mBar): m.p. 208 – 214 C (DSC); 1H N R (CDCI3, 400 MHz) delta 2.38 (s, 6H), 2.49 (s, 6H), 6.71 (dd, J 1.8, 8.7 Hz, 2H), 7.03 (d, J 8.6 Hz, 2H), 7.05 – 7.20 (m, 8H), 7.23 – 7.40 (m, 12H); 13C NMR (CDCI3, 100 MHz) 5 21.2, 21.3, 109.4, 109.4, 115.7, 119.7, 121.8, 122.4, 123.1, 126.5, 127.8, 129.3, 129.6, 130.4, 134.6, 137.4, 139.6, 139.7; HRMS (El) m/z 671.2916 C46H35 6 [M – Hf* requires 671.2918

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; COMMONWEALTH SCIENTIFIC AND INDUSTRIAL RESEARCH ORGANISATION; MACDONALD, James Matthew; BOWN, Mark; UENO, Kazunori; WEBER, Karl Peter; O’CONNELL, Jenny Lee; HIRAI, Tadahiko; WO2012/51666; (2012); 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

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. 16681-56-4, name is 2-Bromo-1H-imidazole, A new synthetic method of this compound is introduced below., SDS of cas: 16681-56-4

Example 242 Trans-4-(4-(imidazol-2-yl)-benzenesulfonylamino)-cyclohexanecarboxylic acid [(R)-1-(4-fluoro-phenyl)-ethyl]-amide Trans-N-((R)-1-(4-fluorophenyl)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonamido)cyclohexanecaboxamide (Intermediate 64, 0.206 mmol), Pd(dppf)Cl2.DCM (19 mg, 0.023 mmol), 2M Na2CO3 (0.57 ml, 1.14 mmol) and 2-bromo-imidazole (17 mg, 0.114 mmol) dissolved in DMF (2 ml) under N2, and the mixture was microwaved at 160 C. for 20 min., after which LCMS indicated that the reaction was complete. The mixture was diluted with DCM and MeOH and filtered through a syringe filter. The filtrate was then passed through a 40+S biotage column with an isocratic gradient of 10% MeOH in EtOAc and the product fractions were combined and concentrated. Crude product was repurified via reverse phase chromatography on prep-HPLC (150 mm, C8 luna, 15-20 min run, 10%-100% MeCN in water containing 0.1% TFA) and the product containing fractions were lyophilized to yield the title compound as a white solid (4.2 mg, 3%). MS MH+ 471.1

The synthetic route of 16681-56-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BARNES, David; BEBERNITZ, Gregory Raymond; COHEN, Scott Louis; DAMON, Robert Edson; DAY, Robert Francis; JAIN, Monish; KARKI, Rajeshri Ganesh; KIRMAN, Louise Clare; PATEL, Tajesh Jayprakash; RAYMER, Brian Kenneth; SCHUSTER, Herbert Franz; ZHANG, Wei; US2011/136735; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 25676-75-9, 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 25676-75-9 as follows.

Example 831 -Methylethyl [(2S,4/?)-1 -acetyl-2-methyl-6-(1 -methyl-1 H-imidazol-4-yl)-1 ,2,3,4- tetrahydro-4-quinolinyl]carbamate h drochlorideA mixture of 1 -methylethyl [(2S,4R)-1 -acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)-1 ,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation, see Intermediate 52) (150 mg, 0.36 mmol), 4-bromo-1 -methylimidazole (0.43 mmol), tetrakis(triphenylphosphine)palladium(0) (42 mg, 10 mol%) and potassium carbonate (199 mg, 1 .44 mmol) in toluene (2 mL) and ethanol (2 mL) was refluxed for 16 h then cooled to room temperature and concentrated in vacuo. The residue was partitioned between AcOEt (10 mL) and water (10 mL) and the layers were separated. The organic phase was dried over MgS04 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 0 to 6% MeOH in DCM) gave a residue which was treated with 1 M HCI in Et20 (0.5 mL, slight excess). The solvent was evaporated and the residue triturated with Et20 to give 1 -methylethyl [(2S,4R)-1 -acetyl-2-methyl-6-(1 -methyl- 1 /-/-imidazol-4-yl)-1 ,2,3,4-tetrahydro-4-quinolinyl]carbamate hydrochloride (8 mg, 0.02 mmol, 5%) as a colourless solid. LCMS (method G): Retention time 0.56 min, [M+H]+ = 371.1

According to the analysis of related databases, 25676-75-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GLAXOSMITHKLINE LLC; DEMONT, Emmanuel, Hubert; GARTON, Neil, Stuart; GOSMINI, Romain, Luc, Marie; HAYHOW, Thomas, George, Christopher; SEAL, Jonathan; WILSON, David, Matthew; WOODROW, Michael, David; WO2011/54841; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 16681-59-7, name is 2-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 16681-59-7, HPLC of Formula: C4H5BrN2

Similarly, compound f1 (6.05 g, 37.6 mmol)Dissolved in tetrahydrofuran (140 mL),Adding hexane solvent and dropping at -78 CAfter 2.5 M n-butyllithium (18 mL, 45.1 mmol),Stir for 1 hour.Then slowly add trimethyl borate (13 mL, 56.4 mmol)After that, stir for 2 hours.Then add 2M hydrochloric acid to neutralize,The product was extracted with ethyl acetate and water.Recrystallization from dichloromethane and hexane gave compound g1 (3.56 g, 77%).Weighed compound g1 (3.16 g, 25.1 mmol),Compound e1 (6.23 g, 25.1 mmol),Tetrakistriphenylphosphine palladium (11g, 10mmol)And potassium carbonate (8.42 g, 60.9 mmol),The weighed reactant was dissolved in toluene (1 L) / EtOH (200 mL) / distilled water (200 mL)The solvent was heated at 90 C for 2 hours.After the reaction is completed, the pressure is concentrated,Extract with ethyl acetate and concentrate.Column chromatography gave Intermediate A1 (4.07 g, 65%).

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; Changchun Hai Purunsi Technology Co., Ltd.; Han Chunxue; Cai Hui; (33 pag.)CN108676034; (2018); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 62366-53-4, 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 62366-53-4 as follows.

EXAMPLE 1 N-[1-(2-[1H-indol-3-yl]ethyl)piperidin-4-yl]-1-methyl-1H-imidazole-2-carboxamide A melt of 3-[2-(4-amino-1-piperidyl)ethyl]indole (1.0 g, 4.11 mmol), 2-hydroxypyridine (0.3 g, 3.16 mmol) and 2-methoxycarbonyl-1-methyl-1H-imidazole (0.57 g, 4.07 mmol) was heated at 160 C. for 3 hours under N2. More 2-methoxycarbonyl-1-methyl-1H-imidazole (5 drops) was added and heating continued for a further 11/2 hours. The mixture was cooled and chromatographed on silica (100-200 aktiv) eluding with absolute ethanol. The title compound was isolated as a brown glass (0.97 g,). This was dissolved in hot ethanol (ca. 10 cm3) and ethanolic HCl added to give an acidic solution from which the dihydrochloride of the title compound crystallized on cooling in ice, 0.48 g, m.p. 250-53 C. (on heating from cold sample gums 140-160 C., crystallises 225-40, starts to decompose at 245 then melts as above). Analysis: Found: C, 56.60; H, 6.23; N, 16.86% C20 H25 N5 0.2HCl requires: C, 56.61; H, 6.41; N, 16.50%.

According to the analysis of related databases, 62366-53-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; John Wyeth & Brother Limited; US4772617; (1988); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 16042-25-4, These common heterocyclic compound, 16042-25-4, name is 2-Imidazolecarboxylic 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.

The synthesis of complex 2 was similarly to 1 except that H3PW12O40¡¤13H2O (0.22g, 0.07mmol) was used instead of H3PMo12O40¡¤26H2O. The pH value was adjusted to 1.8 with molL-1 HNO3 (final pH 2.17). Yellow block crystals were filtered and washed with distilled water (35% yield based on W). Elemental Anal. Calc. for C16H15Ag2N8O49PW12 (3556.09): C 5.39, H 0.42, N 3.15. Found: C 5.43, H 0.47, N 3.11%.

Statistics shows that 2-Imidazolecarboxylic acid is playing an increasingly important role. we look forward to future research findings about 16042-25-4.

Reference:
Article; Tian, Ai-Xiang; Hou, Xue; Ying, Jun; Liu, Guo-Cheng; Ning, Ya-Li; Li, Tian-Jiao; Wang, Xiu-Li; Inorganica Chimica Acta; vol. 439; (2016); p. 43 – 48;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 36947-69-0, 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. 36947-69-0 name is 2-(tert-Butyl)-1H-imidazole, 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.

A microwave tube was charged with 2,6-dibromo-N-tert-butylpyridine-4-carboxamide (intermediate 1, step A) (0.84 g, 2.5 mmol), 2-(tert-butyl)-1H-imidazole (310 mg, 2.5 mmol), potassium phosphate (1.06 g, 5 mmol) and tetrabutylammoniumbromide (403 mg, 1.25 mmol), DMSO (5 ml) was added, the reaction mixture purged with argon for 5 mm in an ultrasonic bath, copper(I)iodide (47.6 mg, 250 tmol) and 4,7-dihydroxy-1,10-phenanthroline (106 mg, 500 tmol) were added, the tube was sealed and the reaction mixture was allowed to stir for 20h at 120C. The reaction mixture was cooled to room temperature, diluted with water (10 nil), and the precipitate collected by filtration. The crude product (950 mg) was purified by flash chromatography on silica gel [heptane/ ethyl acetate (20-80%)j to yield the title compound (494 mg, 52%) as an off-white solid, MS (ISN) mlz = 381.1 [(M+H)i, mp 216C.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-(tert-Butyl)-1H-imidazole, and friends who are interested can also refer to it.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; HOENER, Marius; WICHMANN, Juergen; (65 pag.)WO2017/9274; (2017); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 6160-65-2, A common heterocyclic compound, 6160-65-2, name is 1,1′-Thiocarbonyldiimidazole, molecular formula is C7H6N4S, 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.

Step A: N-(thiazol-2-yl)-1H-imidazole-1-carbothioamide To thiazol-2-amine (2.12 g, 21.17 mmol) in acetonitrile (30 mL) and tetrahydrofuran (5 mL) was added di(lH-imidazol-l-yl)methanethione (4.90 g, 27.5 mmol). The reaction was stirred at 60 C for 5 hours. The reaction was cooled to room temperature and the precipitate was filtered and washed with cold acetonitrile (2 x 15 mL) to afford an orange-brown powder. The product, N-(thiazol-2-yl)-lH- imidazole- l-carbothioamide (3.70 g, 17.60 mmol, 83 % yield), was taken directly to the next step without any further characterization.

The synthetic route of 6160-65-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; COOK II, James H.; MCDONALD, Ivar, M.; KING, Dalton; OLSON, Richard, E.; WANG, Nenghui; IWUAGWU, Christiana, I.; ZUSI, Christopher, F.; MACOR, John, E.; WO2011/53292; (2011); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem