Tag: M.W=100-200

Electric Literature of 29518-68-1, 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. 29518-68-1 name is 2-(1H-Benzo[d]imidazol-2-yl)ethanamine, 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.

General procedure: A suitable round bottom flask or reacti-vial was charged with aryl halide (1 equiv.), tryptamine (1.1 equiv.), IPA (lOmL/mmol) and triethylamine (2 equiv.) and heated at 100C for 3 h (reaction monitored by UPLC analysis). On cooling the reaction mixture was evaporated to dryness and the resultant residue partitioned between ethyl acetate and water. The organic phase was separated and sequentially washed with saturated bicarbonate solution, water, brine, then dried over sodium sulfate, filtered and evaporated. Purification, if required was performed by chromatography or trituration.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-(1H-Benzo[d]imidazol-2-yl)ethanamine, and friends who are interested can also refer to it.

Reference:
Patent; JAGUAHR THERAPEUTICS PTE LTD; METE, Antonio; HITCHIN, James, R,; GRAHAM, Mark; KING-UNDERWOOD, John; THORNE, Philip, Vellacott,; (62 pag.)WO2020/39093; (2020); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 50790-93-7,Some common heterocyclic compound, 50790-93-7, name is 2-Butylimidazole, molecular formula is C7H12N2, 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.

(i) 4-Bromo-2-n-butylimidazole A solution of 20 g (0.16 mol) of 2-n-butylimidazole in 1.2 L of carbon tetrachloride was treated with 57.2 g (0.32 mol) of N-bromosuccinimde and heated with good stirring at 60 for 18 h. Then an additional 10 g of N-bromosuccinimide was added and the heating continued for 4 hours. The solids were collected by filtration. Evaporation of the filtrate gave 15 g of an oily solid which was mostly 2-n-butyl-4,5-dibromoimidazole. Evaporation of the solution obtained by trituration of the initial solids with methylene chloride and concentration gave additional product which was chromatographed over silica (20% ethyl acetate in hexane) to give, when combined with the first fraction, 34.2 g (76%) of dibromo product. A solution of 33.5 g (0.119 mol) of this product in 250 ml of n-propanol was refluxed for 18 hours with a suspension of 100 g (0.794 mol) of sodium sulfite. An additional 50 g of sodium sulfite was added and the mixture refluxed an additional 20 hours. The reaction mixture was concentrated under vacuum, 800 ml of water was added, and then the product was extracted into ether at pH 8. The ether layer was washed with water and brine, dried over sodium sulfate, and concentrated to give 23 g of a solid. Chromatography of the crude product (silica gel, 15-30% ethyl acetate-hexane) gave 7.51 g (31%) of pure 2-n-butyl-4-bromoimidazole.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Butylimidazole, its application will become more common.

Reference:
Patent; SmithKline Beecham Corporation; US5728842; (1998); A;,
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. 67014-36-2, name is 5-Amino-6-methyl-1H-benzo[d]imidazol-2(3H)-one, This compound has unique chemical properties. The synthetic route is as follows., Formula: C8H9N3O

1.59 g (6.13 mmol) of ethyl 3-ethoxy-2-[(ethoxycarbonyl)carbamoyl]acrylate (for preparation see: Senda, Shigeo; Hirota, Kosaku; Notani, Jiyoji, Chemical & Pharmaceutical Bulletin (1972), 20(7), 1380-8) and 1.00 g (6.13 mmol) of 5-amino-6-methyl-1,3-dihydro-2H-benzimidazol-2-one were heated to reflux in 46 ml of ethanol for 2 h. Thereafter, 0.69 g (6.13 mmol) of potassium tert-butoxide were added at RT and the reaction mixture was stirred at RT overnight and at reflux for 1 h. For workup, the reaction mixture was admixed with water and acidified with 1N hydrochloric acid. The solid formed was filtered off, washed with water and ethyl acetate, and then dried under reduced pressure at 50 C. This gave 1.46 g (72% of theory) of the target compound. LC-MS (Method 1): Rt=0.52 min; MS (ESIpos): m/z=331 (M+H)+. 1H NMR (400 MHz, DMSO-d6): delta [ppm]=1.22 (t, 3H), 2.08 (s, 3H), 4.16 (q, 2H), 6.89 (s, 1H), 7.03 (s, 1H), 8.19 (s, 1H), 10.77 (s, 1H), 10.78 (s, 1H), 11.65 (s, 1H).

According to the analysis of related databases, 67014-36-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; Fuerstner, Chantal; Ackerstaff, Jens; Straub, Alexander; Meier, Heinrich; Tinel, Hanna; Zimmermann, Katja; Tersteegen, Adrian; Zubov, Dmitry; Kast, Raimund; Schamberger, Jens; Schaefer, Martina; Boerngen, Kirsten; US2015/148340; (2015); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 4887-82-5, 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 4887-82-5 as follows.

Intermediate 2; M&lbgammal 5-{5~chloro-1 Mbe?2Jm.d8ZthetaJ-1-v.)-3-{[(1/?)-1-(2-chioro~ 3″hvdroxyphe?yi)ethy?oxy}-2-thiophe?ecaphiochiyiateStep A – Methyi 5-(5-chioro-1 AAbenzimida2ol-1-y.)-3-{[(1 ,1-dimethylethyl)- (climethy.)si.y.]oxy}-2-thiophenecarboxyiateTo a mixture of chiorobe?zimidazole (7,0 g, 48 mmol) and methyl 2-chloro-3- oxo-2,3-dihydro-2-thk>phenecarboxyiate (Synthesis,, 1984,, IQ1 847-850) (9.8 g, 51 mmol) in 400 mL of chloroform was added /V-methyiimidazoie (5.5 mL, 89 mmoi). After 16 h, fe/f-buiyfchlorodimethyisilane (8.9 g, 46 mmol) and lambdaA methylimidazoie (3.7 ml, 48 mmol) was added. The reaction mixture was diluted with water and the layers were separated. The aqueous phase was extracted with DCW. The combined organic layers were washed with water, dried over MgSO4 and concentrated onto silica gel The crude material was purified by flash column chromatography (0-100% 25% EtOAc/hexanes) to give 5,8 g of the desired product (30%). 1H NMR (400 MHz, Cl6-DMSO) delta 8.79 (ss 1H), 7.8S (ci, ,/ =2.0 Hz1 IH), 7.81 (d, J =%alpha HZ1 1H)1 7,44 (dd, J^8,8 and 2.0 Hz, 1H), 7,25 (s. 1H), 3.78 (s, 3H), 0.99 (s, 9H), 0.27 (s, QH).

According to the analysis of related databases, 4887-82-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2007/143456; (2007); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 108035-45-6, These common heterocyclic compound, 108035-45-6, name is 4-(1H-Imidazol-2-yl)benzoic 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.

Example 281; 4- (1H-Imidazol-2-yl) -N- ( ( 1R, 2S) -2-{ [ (3aR, 4R, 9bR) -4- (methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2- c]quinolin-1-yl]carbonyl}cyclohexyl)benzamide; To a solution of (1R,25)-2-{[(3aR,4R,9bR)-4- (methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2- c]quinolin-1-yl]carbonyl}cyclohexaneamine hydrochloride (200 mg, 0.480 mmol) in tetrahydrofuran (5 ml) were added triethylamine (0.199 ml, 1.44 mmol), 4-(1H- imidazol-2-yl) benzoic acid (99.0 mg, 0.529 mmol) and DEPC (0.079 ml, 0.529 mmol) under ice-cooling, and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous Mg2S04 and concentrated under reduced pressure. The obtained residue was subjected to column chromatography using silica gel and eluted with ethyl acetate-methanol (1: 0-4:1) to give the title compound (150 mg, 61%) as an amorphous form. ¹H-NMR (CDCl3) No.: 1.25-2.50 (11H, m) , 2.96-2.99 (lH, m), 3.34-3.42 (5H, m), 3.54-3.57 (2H, m), 3.70-3. 72 (1H, m), 4.17 (lH, m), 4.30 (lH, m), 5.64 (lH, d, J=6.6 Hz), 6.52 (1H, d, J=7.5 Hz), 6.68 (1H, dd, J=7.5,7.5 Hz), 7.02 (lH, dd, J=7.5,7.5 Hz), 7.15-7.20 (2H, m), 7.36 (lH, d, J=7.5 Hz), 7.42 (lH, d, J=7.5 Hz), 7.83-7.93 (4H, m). LC/MS (ESI) m/z: 514 (MH(at)).

Statistics shows that 4-(1H-Imidazol-2-yl)benzoic acid is playing an increasingly important role. we look forward to future research findings about 108035-45-6.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; WO2005/105802; (2005); 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. 176244-21-6, name is 5,6-Difluoro-1H-benzo[d]imidazol-2(3H)-one, A new synthetic method of this compound is introduced below., name: 5,6-Difluoro-1H-benzo[d]imidazol-2(3H)-one

Example 2; Synthesis of 1 -(4-amino-6-methyl- 1 ,3 ,5 -triazin-2-yl)-5 ,6-difluoro-N-( 1 H-pyrazol-5 -yl)- 1 H- benzo[d]imidazol-2-amine; Step l; A sealable vial was charged with l,2-diamino-4,5-difluorobenzene (66.4 mg, 461 mumol), THF (1 rnL), then l,l’-carbonyldimidazole (CDI) (112 mg, 691 mumol). The resulting reaction mixture was maintained at rt for 18 h. The solution was absorbed onto a 5 g silica loading cartridge and passed through a Redi-Sep pre-packed silica gel column (12 g) using a gradient of 1% MeOH in CH2Cl2 to 10% MeOH in CH2Cl2 to afford 5,6-difluoro-lH- benzo[d]imidazol-2(3H)-one as a colorless solid, which was contaminated with CDI biproducts. The solid was transferred to a vial and phosphorus oxychloride (1.265 mL, 13.82 mmol) was added. The reaction mixture was stirred and heated at 90 0C for 18 h and then concentrated for purification by MPLC (Teledine Isco combiFlash Companion). The crude residue was taken up in minimal CH2Cl2 and absorbed onto a 5 g silica loading cartridge and passed through a Redi-Sep pre-packed silica gel column (12 g) using a gradient of 2% EtOAc in hexanes to 90% EtOAc in hexanes to afford 2-chloro-5,6-difluoro-lH- benzo[d]imidazole (49.0 mg, 56.4% yield) as a colorless solid.

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; AMGEN INC.; BOEZIO, Alessandro; CHENG, Alan, C.; COATS, James, R.; COPELAND, Katrina, W.; GRACEFFA, Russell; HARMANGE, Jean-Christophe; HUANG, Hongbing; LA, Daniel; OLIVIERI, Philip, R.; PETERSON, Emily, A.; SCHENKEL, Laurie; WO2010/96314; (2010); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 10394-39-5, name is 5-Methoxy-1-methyl-1H-benzo[d]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 10394-39-5, Formula: C9H10N2O

To a solution of 198 5-methoxy-1-methyl-1H-benzo[d]imidazole (500 mg, 3.08 mmol) in 200 CH2Cl2 (6 ml) was added 201 BBr3 (3.1 g, 12.33 mmol) dropwise at 0 C. After addition, the mixture was stirred for 2 h at 0 C. The mixture was then quenched by slow addition to 202 ice water (50 mL). The resulting mixture was extracted with CH2Cl2 (2×20 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4 and concentrated to give the 203 title compound (100 mg, 21.9%) as a white solid which was used in next step without further purification. LCMS (m/z): 149.1 (M+1).

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, 5-Methoxy-1-methyl-1H-benzo[d]imidazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Epizyme, Inc.; Duncan, Kenneth W.; Chesworth, Richard; Boriack-Sjodin, Paula Ann; Munchhof, Michael John; Jin, Lei; (118 pag.)US2019/83482; (2019); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 184098-19-9, 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. 184098-19-9, name is 3-(2-Methyl-1H-imidazol-1-yl)aniline, This compound has unique chemical properties. The synthetic route is as follows.

A cooled (0 0C) solution of 6-(cyclopropylmethyl(propyl)amino)pyrimidine-4- carboxylic acid (Intermediate 21 , 112 mg; 0.45 mmol) in DCM was treated with diisopropylethylamine (78.4 mL; 0.52 mmol) and methyl chloroformate (36.2 mL; 0.47 mmol). After stirring at 0 0C for 15 minutes, 3-(2-methyl-1 H- imidazol-1-yl)aniline (Maybridge, 117 mg; 0.67 mmol) was added and the mixture stirred for 72 hours. The solvent was evaporated and the compound purified by preparative HPLC to give the title compound as a white solid. 1H NMR (400MHz, CDCI3) delta 10.11 (1 H, s), 8.57 (1 H, s), 7.98 (1 H, t, J = 2.1 Hz), 7.64 (1 H, dd, J = 8.2, 2.0 Hz), 7.47 (1 H, t, J = 8.0 Hz), 7.35 (1 H, s), 7.09- 7.02 (3H, m), 3.53 (4H, s), 2.43 (3H, s), 1.76-1.64 (2H, m), 1.09 (1 H, m), 0.97 (3H, t, J = 7.3 Hz), 0.57 (2H, d, J = 7.7 Hz), 0.35-0.29 (2H, m). MS (ESI+) 391. HPLC (Condition C) Rt 2.33 min (HPLC purity 99.8%).

The chemical industry reduces the impact on the environment during synthesis 3-(2-Methyl-1H-imidazol-1-yl)aniline. I believe this compound will play a more active role in future production and life.

Reference:
Patent; LABORATOIRES SERONO SA; WO2009/19167; (2009); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 50790-93-7, name is 2-Butylimidazole, 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 50790-93-7, Formula: C7H12N2

Preparation of 6-(2-butylimidazol- 1 -vD-2-chloropurine. A solution of 9-(2,3,5-tri-0-acetyl-beta-D-ribofuranosyi)-2,6-dichloropurine(2.41 g, 5.4 mmol) and 2-butylimidazole (6.68 g, 54 mmol) in CH3CN (60 mL) was stirred at 65 C under N2 for 32 h (reaction complete, TLC). Volatiles were evaporated in vacuo, and the residue was chromatographed (MeOHZCH2Cl2, 1:90) to give crude 9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-6-(2-butylimidazol-l-yl)-2- chloropurine (3.33 g, contaminated with 2-butylimidazole): 1H NMR (500 MHz,CDCl3) delta 8.56 (s, IH), 8.24 (s, IH), 7.10 (s, IH), 6.26 (d, J= 5.8 Hz, IH), 5.83 (t, J = 5.6 Hz, IH), 5.61 (t, J= 5.6 Hz, IH), 4.43-4.51 (m, 3H), 3.31 (t, J= 7.9 Hz, 2H), 2.18 (s, 3H), 2.16 (s, 3H), 2.11 (s, 3H), 1.81 (quint, J= 7.7 Hz, 2H), 1.50 (sext, J= 7.7 Hz, 2H), 0.98 (t, J= 7.3 Hz, 3H); HRMS m/z 535.1702 (MH+ [C23H28ClN6O7] = 535.1708).

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, 2-Butylimidazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BRIGHAM YOUNG UNIVERSITY, TRANSFER TECHNOLOGY OFFICE; WO2006/138396; (2006); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 115576-91-5, A common heterocyclic compound, 115576-91-5, name is (1-Methyl-1H-benzo[d]imidazol-5-yl)methanol, molecular formula is C9H10N2O, 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 11C : [1-METHYLBENZIMIDAZOLE-5-CARBOXALDEHYDE] A solution of 5-hydroxymethyl-1-methylbenzimidazole (0.8 g, 4 mmol) in acetone (40 [ML)] was treated with [MN02] (4 g) and the mixture was stirred for 3 days. The solid was filtered off and the solvent removed under reduced pressure to give 0.63 g of product. [COHGN2O] Mass (calculated): [160]; (found): [M+H+] = 161. NMR (400 [MHZ, DMSO-D6)] : 3.95 (3H, s, NCH3) ; 7.8 [(1H,] d, J = 8 Hz, aryl-H); 7.9 [(1H,] dd, [J =] 1 and 8 Hz, aryl-H); 8.3 [(1H,] d, J= 1 Hz, aryl-H); 8.45 [(1H,] s, imidazole-H); 10.1 [(1H,] s, CHO).

The synthetic route of 115576-91-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AMGEN, INC.; WO2003/99814; (2003); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem