Month: September 2021

Application of 53484-18-7, These common heterocyclic compound, 53484-18-7, name is 1-Methyl-1H-benzo[d]imidazole-6-carboxylic 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.

Compound 1 (50 mg, 0.28 mmol), tert-butyl 2-amino-4-(thiophen-2- yl)phenylcarbamate (66 mg, 0.23 mmol), and EDCI (164 mg, 0.85 mmol) were combined in Py (3 ml_). The reaction was stirred at rt overnight. After completed, the mixture was concentrated and washed with water and ether. The white solid was afforded as Compound 2 (100 mg, 72%).

The synthetic route of 53484-18-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; REGENACY PHARMACEUTICALS, LLC; VAN DUZER, John, H.; MAZITSCHEK, Ralph; BLUM, Charles; (70 pag.)WO2020/68950; (2020); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 39070-14-9,Some common heterocyclic compound, 39070-14-9, name is (1-Methyl-2-nitro-1H-imidazol-5-yl)methanol, molecular formula is C5H7N3O3, 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 alcohol18(1.0 g, 6.36 mmol) in chloroform (70 mL) was added MnO2(2.76 g, 31.8 mmol) and the mixture was heated to reflux overnight. After cooling, the resulting slurry was filtered through diatomaceous earth and solvent removed in vacuo to yield19(1.5 g, 76%) as a pale yellow solid, mp 112-114 C (lit. [62] mp 114-115 C). deltaH(CDCl3) 9.93 (1H, s, CHO), 7.81 (1H, s, H-4), 4.36 (3H, s, CH3). deltaC(CDCl3) 180.4 (C = O), 148.3 (C-NO2), 139.4 (CH), 132.4 (CH), 35.6 (CH3). LRMS 188.1 (100%, M + CH3OH). These data are in good agreement with literature values [35].

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (1-Methyl-2-nitro-1H-imidazol-5-yl)methanol, its application will become more common.

Reference:
Article; Dickson, Benjamin D.; Wong, Way Wua; Wilson, William R.; Hay, Michael P.; Molecules; vol. 24; 8; (2019);,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature 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

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 78581-99-4 as follows. Recommanded Product: 78581-99-4

Step 3: To a stirred mixture of sodium hydride (60% dispersion in mineral oil, 0.144 g, 3.0 mmol) in anhydrousDMF (10 mL) at 0 C under a nitrogen atmosphere was added portionwise 6-difluoro-1H-benzo[d]imidazole (0.475 g,2.0 mmol) from the previous step. The mixture was stirred at 0 C for 5 min. To the mixture was added dropwise asolution of 6-(chloromethyl)-2-(methylthio)benzo[d]thiazole (0.32 g, 2.0 mmol) from Step 4 of Example 36 in anhydrousDMF (2 mL). The reaction mixture was allowed to warm to rt and stir for 1 h. The mixture was poured into ice-water andextracted with EtOAc (100 mL 3 2). The combined organic layers were further washed with water (20 mL) then brine(20 mL). The organic layer was separated and dried over Na2SO4, filtered, and concentrated under reduced pressureto afford 6-((5,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylthio)benzo[d]thiazole (0.55 g, 76%) as a yellow solid,which was not purified further. 1H NMR (300 MHz, CDCl3) delta 7.97 (s, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.59 (m, 1H), 7.50(s, 1H), 7.24 (m, 1H), 7.02 (m, 1H), 5.40 (s, 2H), 2.78 (s, 3H); LCMS (ESI) m/z 348 (M + H)+.

According to the analysis of related databases, 78581-99-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Ambit Biosciences Corporation; HADD, Michael J.; HOCKER, Michael D.; HOLLADAY, Mark W.; LIU, Gang; ROWBOTTOM, Martin W.; XU, Shimin; (299 pag.)EP2766359; (2016); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Synthetic Route of 3314-30-5, 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. 3314-30-5, name is 1H-Benzo[d]imidazole-2-carbaldehyde belongs to imidazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

A 20 mL vial was charged with a 1.5 mL of ammonium acetate/acetic acid buffer solution (pH 4) in methanol. To this Example 87D (35.24 mg, 0.109 mmol) was added to form a suspension. lH-benzo[d]imidazole-2-carbaldehyde (23.89 mg, 1.5 eq, 0.164 mmol) and Si-BH3CN (from Silicycle, 0.88mmol/g loading, 371.49 mg) were then added. The vial was capped and placed to stir at 40°C overnight. Upon completion, the crude mixture was filtered, concentrated, and purified by HPLC (see Example 360 for protocols) to provide the title compound as a trifluoroacetic acid salt. lH NMR (400 MHz, pyridine-d5) delta ppm 2.57 (q, J = 4.1, 3.2 Hz, 2H), 2.83 (t, J = 5.7 Hz, 2H), 3.39 (q, J = 2.8 Hz, 2H), 3.71 (s, 3H), 4.17 (s, 2H), 6.61 (s, 1H), 6.64 – 6.67 (m, 1H), 7.09 (dd, J = 9.1, 4.5 Hz, 1H), 7.26 (ddd, J = 9.1, 7.9, 3.2 Hz, 1H), 7.32 (d, J = 4.9 Hz, 1H), 7.34 – 7.39 (m, 2H), 7.49 (dd, J = 8.9, 3.2 Hz, 1H), 7.89 (dd, J = 6.0, 3.2 Hz, 2H), 8.58 (d, J = 5.0 Hz, 1H). MS (ESI+) m/z 454.2 (M+H)+.

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, 1H-Benzo[d]imidazole-2-carbaldehyde, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ABBVIE INC.; ABBVIE PHARMACEUTICAL TRADING (SHANGHAI) CO., LTD.; TONG, Yunsong; BRUNCKO, Milan; CLARK, Richard F.; CURTIN, Michael L.; FLORJANCIC, Alan S.; FREY, Robin R.; GONG, Jianchun; HANSEN, Todd M.; JI, Zhiqin; LAI, Chunqiu; MASTRACCHIO, Anthony; MICHAELIDES, Michael; MIYASHIRO, Juliem; RISI, Roberto M.; SONG, Xiaohong; TAO, Zhi-fu; WOODS, Keith W.; ZHU, Guidong; PENNING, Thomas; SOUERS, Andrew; GOSWAMI, Rajeev; IQUTURI, Omprakash Reddy; DABBEERU, Madhu Babu; WO2014/139328; (2014); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Some common heterocyclic compound, 288-32-4, name is 1H-Imidazole, molecular formula is C3H4N2, 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. Application In Synthesis of 1H-Imidazole

Step 1. Synthesis of 4-chloro-1H-imidazole (C33) To a solution of 1H-imidazole (22.1 g, 324 mmol) in N,N-dimethylformamide at 0 C. was added drop-wise (over 4 hours) a solution of N-chlorosuccinimide (25 g, 190 mmol) in N,N-dimethylformamide (total solvent, 160 mL). The reaction was stirred at 0 C. for 1 hour, whereupon water (200 mL) was added at 0 C. The mixture was extracted with ethyl acetate (3*50 mL), and the combined organic layers were concentrated in vacuo. Purification was carried out using supercritical fluid chromatography (Column: Princeton Cyano, 5 mum; Eluant: 15:85 methanol/carbon dioxide). The resulting material was purified again, using silica gel chromatography (Mobile phase A: ethyl acetate; Mobile phase B: [20% (2 M ammonia in methanol) in dichloromethane]; Gradient: 0% to 10% B) to afford the title compound as a white solid. Yield: 2.45 g, 23.9 mmol, 12%. GCMS m/z 102, 104 (M+). 1H NMR (400 MHz, CDCl3) delta 7.00 (d, J=1.2 Hz, 1H), 7.57 (br s, 1H), 11.3 (v br s, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 288-32-4, its application will become more common.

Reference:
Patent; Pettersson, Martin Youngjin; Johnson, Douglas Scott; Subramanyam, Chakrapani; O’Donnell, Christopher John; Ende, Christopher William Am; Fish, Benjamin Adam; Green, Michael Eric; Mullins, Patrick Bradley; Stiff, Cory Michael; Tran, Tuan Phong; Navaratnam, Thayalan; US2012/252758; (2012); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 2302-25-2, name is 4-Bromo-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 2302-25-2, Computed Properties of C3H3BrN2

(i) Production of (1H-Imidazol-4-yl)-(naphthalen-2-yl)ketone 4-Bromo-1H-imidazole (1.95 g) was dissolved in THF (30 ml), and the solution was cooled to -78 C. To the solution was added a solution of t-butyllithium in pentane (1.7 M; 20 ml). The mixture was stirred at 0 C. for 1.5 h. The mixture was again cooled to -78 C., and a solution of 2-formylnaphthalene (3.32 g) in THF (20 ml) was added. After the temperature was elevated from -78 C. to room temperature, the mixture was stirred at room temperature for 16 h. To the mixture was added an aqueous solution of ammonium chloride, and the mixture was extracted with ethyl acetate. The organic layer was dried and concentrated. The residue was purified by silica gel column chromatography,(eluent, dichloromethane_methanol=10:1). Recrystallization from dichloromethane-methanol gave the titled compound (1.00 g) as a colorless solid. 1H-NMR (CDCl3) delta: 7.53-7.70 (2H, m), 7.84-8.40 (6H, m), 8.53 (1H, s), 10.82 (1H, brs). IR (KBr): 2592, 1640, 1127, 779 cm-1.

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; Takeda Chemical Industries, Ltd.; US6573289; (2003); B1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 46006-36-4, 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 46006-36-4 as follows.

3H-Benzoimidazole-4-carboxylic acid[3-(1H-tetrazol-5-yl)-phenyl]-amide (16) 3-(1H-Tetrazol-5-yl)aniline (75 mg, 0.47 mmol), 1H-benzimidazole-4-carboxylic acid (76 mg, 0.47 mmol), 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (135 mg, 0.7 mmol), 1-hydroxybenzotriazole (95 mg, 0.7 mmol) and N,N’-diisopropylethylamine (0.17 mL, 0.94 mmol) was stirred in DMF (0.5 mL) at room temperature for 24 h. The reaction mixture is diluted with water (2 mL) and after approximately adjusting the pH to 4 with 1N HCl, the mixture was extracted with ethyl acetate. The organic extracts were washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The crude material was purified by reverse phase HPLC to afford the product as a trifluoroacetic acid salt in 5% yield. 1H NMR (DMSO-d6) delta 8.62 (s, 1H), 8.53 (s, 1H), 7.99-8.02 (m, 3H), 7.86 (d, J=8 Hz, 1H), 7.77 (d, J=4 Hz, 1H), 7.62 (t, J=8 Hz, 1H), 7.43 (t, J=8 Hz, 1H), 7.04 (s, 1H); LCMS (ESI) m/z 306 (MH+).

According to the analysis of related databases, 46006-36-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; UNIVERSITY OF SOUTH FLORIDA; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; Chen, Yu; Nichols, Derek; Renslo, Adam R.; Jaishankar, Priyadarshini; Lauterwasser, Erica M. W.; (29 pag.)US9556131; (2017); B2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Electric Literature of 144689-93-0, 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 144689-93-0 as follows.

Example 6:; (5-MethyI-2-oxo-l,3-dioxol-4-yI)methyl 5-(2-hydroxypropan-2-yl)-2-propyl-3-[[4-[2- (2H-tetrazoI-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylate (olmesartan medoxomil) (Ie); Step I: 5-(2-Hydroxypropan-2-yl)-2-propyl-3-[[4-[2-(N-(2-trimethylsilylethoxymethyl) tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-ethylcarboxylate (Vd); 2-Propyl-5-[(l-hydroxy-l-methyl)ethyl]-3H-imidazole-4-ethylcarboxylate (0.808 g, 0.0033675 mol) was added to the two isomers (IVb) (1.5 g, 0.0033675 mol) and K2CO3 (0.558 g, 0.0040382 mol) in anhydrous DMF (10 mL) under N2 atmosphere. The mixture was stirred at room temperature for 17 hrs (TLC monitoring: cyclohexane/AcOEt 6:4). The mixture was partitioned between water and AcOEt. The organic layer was washed with water (3 times), dried over Na2SO4 and concentrated under reduced pressure to give a residue (1.8 g) that was purified by flash chromatography on silica (cyclohexane/AcOEt 6:4) to give the isomer (Vd1) (0.499 g) and the isomer (Vd2) (0.206 g) as oils. Yield: 35%. (Vd1) (isomer with lower elution time):1H-NMR (400 MHz, CDCl3, delta): -0.03 (s, 9H, Me3Si), 0.92 (t, J=8.2Hz, 2H, SiCH2CH2O), 0.96 (t, J=7.2Hz, 3H, CH2CH2CH3), 1.18 (t, J=7.2etaz, 3H, OCH2CHi), 1.64 (s, 6eta, CMe2), 1.67-1.76 (m, 2H5 CH2CH2CH3), 2.66 (t, J=7.6Hz, 2H, CH2CH2CH3), 3.66 (t, J=8.2Hz, 2H, SiCH2CH2O), 4.22 (q, J=7.2etaz, 2H, OCH2CH3), 5.44 (s, 2H, ArCH2N), 5.78 (s, 2H, OCH2N), 6.84-6.86 (m, 2H) 7.14-7.16 (m, 2H) 7.41-7.43 (m, IH) 7.46-7.56 (m, 2H) 7.84- 7.86 (m, IH) (aromatic protons).(Vd2) (isomer with higher elution time): 1H-NMR (400 MHz, CDCl3, delta): -0.10 (s, 9H, Me3Si), 0.70 (t, J=8.4Hz, 2H, SiCH2CH2O), 0.92 (t, J=7.4Hz, 3H, CH2CH2CH5), 1.13 (t, J=7.0etaz, .3eta, OCH2CH3), 1.60 (s, 6eta, CMe2), 1.62-1.71 (m, 2H, CH2CH2CH3), 2.58 (t, J=7.8Hz, 2H, CH2CH2CH3), 3.39 (t, J=8.4Hz, 2H, SiCH2CH2O), 4.17 (q, J=7.2etaz, 2H, OCH2CH3), 5.05 (s, 2H, ArCH2N), 5.38 (s, 2H, OCH2N), 6.81-6.83 (m, 2H) 7.05-7.07 (m, 2H) 7.49-7.52 (m, 2H) 7.55-7.57 (m, IH) 7.61- 7.65 (m, IH) (aromatic protons). Step II: 5-(2-Hydroxypropan-2-yl)-2-propyl-3-[[4-[2-(N-(2-trimethylsilylethoxymethyl) tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid (Ve i); A solution of NaOH (0.052 g, 0.001311 mol> in water (1 mL) was added to compound (VdO (0.262 g, 0.0004337 mol) in THF (1 mL). The mixture was stirred at room temperature for 23 hrs (TLC monitoring: CH2Cl2/MeOH/AcOH 85:10:5). HCl IN was added until pH 4 was reached. The mixture was extracted with AcOEt. The organic phase was dried over Na2SO4 and concentrated under reduced pressure to give the compound (Vei) (0.261 g) as a white solid, m.p. 68-69C. Yield: 99%. 1H-NMR (400 MHz, CDCl3, delta): -0.05 (s, 9H, Me3Si), 0.86 (t, J-7.2Hz, 3H, CH2CH2CH3), 0.89 (t, J=8.1etaz, 2H, SiCH2CH2O), 1.54-1.60 (m, 2H, CH2CH2CH3) 1.67 (s, 6H, CMe2), 2.94 (t, J-7.2Hz, 2H, CH2CH2CH3), 3.65 (t, J=8.1Hz, 2H, SiCH2CH2O), 5.75 (s, 2eta, ArCH2N), 5.79 (s, 2H, OCH2N), 6.97-6.99 (m, 2H) 7.12-7.14 (m, 2H) 7.35-7.38 (m, IH) 7.44-7.53 (m, 2H) 7.83-7.85 (m, IH) (aromatic protons). Step III: 4-Bromomethyl-5-methyl~l,3-dioxol~2-one; A mixture of 4,5-dimethyl-l,3-dioxol-2-one (1.5 g, 0.013158 mol), NBS (2.34 g, 0.013158 mol) and benzoyl peroxide (0.089 g, 0.0003684 mol) in CCl4 (20 mL) was stirred at 77C for 6 hrs (TLC monitoring: cyclohexane/AcOEt 6:4). The solution was treated with an aqueous solution OfNaHCO3 and extracted with CH2Cl2. The organic phase was dried over Na2SO4 and concentrated under reduced pressure to give 4-bromomethyl-5 -methyl- 1,3- dioxol-2-one (2.34 g). Yield: 92%.1H-NMR (400 MHz, CDCl3, delta): 2.13 (s, 3H, CH3), 4.18 (s, 2H, CH2Br). Stp IV: (5-Methyl-2-oxo-l,3-dioxol-4-yl)methyl 5-(2~hydroxypropan-2-yl)-2-propyl-3-[[4- [2-(N-(2-trimethylsilylethoxymethyl)tetrazol-5-yl)pherpsil]phenyl]methyl]imidazole-4- carboxylate (Vf1); A mixture of the compound (Ve1) (0.260 g, 0.0004516 mol), 4-bromomethyl-5-methyl-l,3- dioxol-2-one (0.1 g, 0.000518 mol) and K2CO3 (0.033 g, 0.000239 mol) in anhydrous DMF (1.5 mL) was stirred for 1.5 hrs at room temperature under N2 atmosphere (TLC monitoring: CH2Cl2/Me0H/Ac0H 85:10:5). The mixture was partitioned between a saturated solution of NaHCO3 and AcOEt. The organic phase was washed with water (3 times), dried over Na2SO4 and concentrated under reduced pressure to give the compound (Vf1) (0.3042g) as a yellow oil. Yield: 98%.1H-NMR (400 MHz, CDCl3, delta): -0.02 (s, 9H, Me3Si), 0.92 (t, J=8.1Hz, 2H, SiCH2CH2O), 0.98 (t, J=7.2Hz, 3H, CH2CH2CH3), 1.64 (s, 6eta, CMe2), 1.70-1.80 (m, 2H, CH2CH2CH3), 2.07 (s, 3H, CH3C=C), 2.76 (m, 2H, CH2CH2CH3), 3.67 (t, J=8.1Hz, 2H, SiCH2CH2O), 4.89 (s, 2eta, COOCH2), 5.41 (s, 2H, ArCH2N), 5.79 (s, 2H, OCH2N), 6.80-6.82 (m, 2H) 7.14-7.16 (m, 2H) 7.44-7.52 (m, 2H) 7.54-7.58 (m, IH) 7.85-7.87 (m, IH) (aromatic protons). Step V: (5-Methyl-2-oxo-l,3-dioxol-4-yl)methyl 5-(2-hydroxypropan-2-yl)~2~propyl~3-[[4- [2~(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylate (olmesartan medo…

According to the analysis of related databases, 144689-93-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; S.I.M.S. S.r.l. – SOCIETA ITALIANA MEDICINALI SCANDICCI; WO2008/12852; (2008); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem