Month: June 2021

Synthetic Route of 328-73-4,Some common heterocyclic compound, 328-73-4, name is 1-Iodo-3,5-bis(trifluoromethyl)benzene, molecular formula is C8H3F6I, 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 2-dram vial equipped with a magnetic stir bar was charged with the amide substrate (36.5 mg, 0.10 mmol), Pd(OAc)2 (2.2 mg, 10 molpercent) , ligand L19 (4.1 mg, 20 molpercent), AgOAc (50 mg, 0.30 mmol) and norbornene (14.1 mg, 0.15 mmol). Aryl iodide (0.30 mmol) and 1.0 mL of t-butyl methyl ether were then added to the mixture. The vial was capped and closed tightly. The mixture was stirred at 95 °C for 12 hours . After cooling to room temperature, the mixture was passed through a pad of Celite® with ethyl acetate as the eluent to remove all the insoluble compounds. The resulting solution was concentrated, and the residual mixture was dissolved with a minimal amount of acetone and loaded onto a preparative TLC plate. The pure product was then isolated by preparative TLC with ethyl acetate and hexanes as the eluent. 2- { 5- [2- (Me hoxycarbonyl) henyl] -2-methylphenyl } – N- [2 , 3 , 5 , 6-tetrafluoro-4- (trifluoromethyl) phenyl] – ace amide Preparative TLC using hexanes/EtOAc (4/1) as the eluent provided the pure product as a white solid (64percent yield). NMR (600 MHz, acetone-d6) delta 9.54 (br, 1H, N-H) , 7.75 (d, J = 7.6 Hz, 1H) , 7.59 (t, J = 7.6 Hz, 1H) , 7.46 (t, J = 7.6 Hz, 1H) , 7.44 (d, J = 7.6 Hz, 1H) , 7.30 (d, J = 1.4 Hz, 1H) , 7.27 (d, J = 7.7 Hz, 1H) , 7.17 (dd, J = 7.7, 1.4 Hz, 1H) , 3.97 (s, 2H) , 3.60 (s, 3H) , 2.41 (s, 3H) ; 13C NMR (150 MHz, acetone-d6) delta 169.70, 169.43, 142.44, 139.82, 137.14, 134.19, 132.37, 132.01, 131.35, 131.26, 130.96, 130.31, 128.03, 127.96, 52.15, 41.17, 19.40. HRMS (ESI-TOF) m/z Calcd for C24Hi7F7N03+ [M+H] + 500.1091, found 500.1090. 6 Equivalents of Arl was used, and AgOAc was replaced by AgOPiv (3 eq. ) in this reaction. Column chromatography using hexanes/EtOAc (4/1) as the eluent provided the pure product as a white solid (76percent yield). XH NMR (400 MHz, acetone-d6) delta 9.62 (br, 1H, N-H) , 8.28 (s, 2H) , 8.02 (s, 1H) , 7.86 (d, J = 2.0 Hz, 1H) , 7.71 (dd, J = 8.0, 2.0 Hz, 1H) , 7.40 (d, J = 8.0 Hz, 1H) , 4.06 (s, 2H) , 2.44 (s, 3H) ; 13C NMR (150 MHz, acetone-d6) delta 169.33, 144.09, 139.45, 136.35, 135.64, 132.65 (q, J = 33.0 Hz), 132.08, 130.11, 127.93, 127.00, 124.54 (q, J = 270.0 Hz), 121.43 (m) , 41.20, 19.40. HRMS (ESI-TOF) m/z Calcd for C24Hi3F13 O+ [M+H]+ 578.0784, found 578.0785.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Iodo-3,5-bis(trifluoromethyl)benzene, its application will become more common.

Reference:
Patent; THE SCRIPPS RESEARCH INSTITUTE; YU, Jin-Quan; (107 pag.)WO2016/123361; (2016); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

3032-81-3, name is 1,3-Dichloro-5-iodobenzene, belongs to iodides-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Recommanded Product: 1,3-Dichloro-5-iodobenzene

General procedure: A suspension of coupling substrate 2d?g (1 equiv), copper(I) iodide (0.5 equiv), cesium carbonate (2 equiv), and the corresponding aryl halide (1 equiv) in dioxane was placed under a nitrogen atmosphere. The coupling ligand DMEDA (1 equiv) was added dropwise by using a syringe and the mixture was then stirred at r.t. for various periods of time (2.5?48 h). At the end of the reaction, all insoluble salts deposited after cooling at r.t. were collected by filtration then washed with dichloromethane. The resulting filtrate was concentrated in vacuo and the residue was partitioned between water and dichloromethane. The organic layer was dried over MgSO4 and evaporated to dryness. The reaction residues were recrystallized or purified by chromatography on silica gel column to afford pure compounds 36?39.

The synthetic route of 3032-81-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Baudelet, Davy; Daich, Adam; Rigo, Benoit; Lipka, Emmanuelle; Gautret, Philippe; Homerin, Germain; Claverie, Christelle; Rousseau, Jolanta; Abuhaie, Cristina-Maria; Ghinet, Alina; Synthesis; vol. 48; 14; (2016); p. 2226 – 2244;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Some common heterocyclic compound, 401-81-0, name is 1-Iodo-3-(trifluoromethyl)benzene, molecular formula is C7H4F3I, 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. Safety of 1-Iodo-3-(trifluoromethyl)benzene

The mixture of Intermediate-51a (150mg, 0.45mmol), l-iodo-3(trifluoromethyl)benzene (0.18g,0.68 mmol) and CS2CO3 (0.22 g, 0.68 mmol) in toluene (7mL) was degassed for 15 min by purging nitrogen followed by addition of bis (tri-tert-butylphosphine palladium(O) (11.53mg, 0.023 mmol) and tris dibenzylidene acetone dipalladium (0)(20.66mg,0.023 mmol). The reaction mixture was heated to 110C and further maintained for 20 hr at the same temperature. The reaction mixture was cooled to room temperature and progress of reaction monitored by TLC. The mixture was diluted with ethyl acetate, filtered through celite and concentrated under vacuum to give crude compound. This crude compound was further purified by flash chromatography using a mixture of 20% ethylacetate in hexane (0.17g, 79%).Ethereal HCl (2 mL) was added and stirred for 10 min. The solvent was evaporated and solid washed by diethyl ether (2 mL) followed by «-pentane (2 ml), dried to get HCl salt of title compound.m/z 477.2; *H NMR (400 MHz, DMSO-d6): delta 9.64 (bs, IH), 9.10 (bs, IH), 8.24 (d, 7=8.4 Hz, IH), 8.03 (t, 7=8.8 Hz, 2H), 7.89 (d, 7=7.2 Hz, IH), 7.63-7.48 (m, 6H), 7.37(d, 7=7.6 Hz, IH), 6.93 (d, 7=7.2 Hz, IH), 6.80-6.77 (m, 3H), 5.34 (m, lH), 4.28 (m, 1H),3.85 (m, lH), 3.47-3.10 (m, 3H), 2.03 (m, 2H), 1.67 (d, 7=6.8 Hz, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 401-81-0, its application will become more common.

Reference:
Patent; LUPIN LIMITED; SHUKLA, Manojkumar, Ramprasad; ANKUSH, Sarde, Gangaram; VIPUL, Pachpute, Dilip; KULKARNI, Sanjeev, Anant; PALLE, Venkata, P.; KAMBOJ, Rajender, Kumar; WO2012/127385; (2012); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Application of 627-31-6, 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. 627-31-6 name is 1,3-Diiodopropane(stabilized with Copper chip), 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.

Example 19Synthesis of: 4-((/?)-2-amino-3-((/?)-2,3-bis(dodecanoyloxy)propylthio)propanamido)-l,l- difluorobutylphosphonic acidStep 1: diethyl 1 ,1 -difluoro-4-iodobut lphosphonate[000492] To a solution of diisopropylamine (1.6 eq) in THF (1.28 M) was slowly added n- butyllithium (1.5 M in cyclohexane, 1.5 eq) dropwise at 0 C. The reaction mixture was stirred at 0 C for 40 minutes. The mixture was then cooled down to -78 C, and diethyldifluoromethylphosphonate (1 eq) in HMPA (2.1 M) was slowly added to the reaction. Then the mixture was stirred at -78 C for 40 minutes and to the resulting solution was added a cooled solution of 1,3-diiodopropane (12.8 M in THF, 4 eq) rapidly. After 1.5 hours, the reaction was quenched by pouring into saturated NH4C1 solution. The aqueous phase was extracted with ethyl acetate three times. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate and concentrated en vaccuo. The resulting crude was purified by flashchromatography on a COMBIFLASH system (ISCO) using 10-100% EtOAc/Hex to give the product as a yellow oil.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1,3-Diiodopropane(stabilized with Copper chip), and friends who are interested can also refer to it.

Reference:
Patent; IRM LLC; WU, Tom Yao-Hsiang; ZOU, Yefen; HOFFMAN, Timothy Z.; PAN, Jianfeng; WO2011/119759; (2011); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Adding a certain compound to certain chemical reactions, such as: 35453-19-1, name is 5-Amino-2,4,6-triiodoisophthalic acid, belongs to iodides-buliding-blocks 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 35453-19-1, Computed Properties of C8H4I3NO4

A. Preparation of 5-Amino-2,4,6-triiodoisophthaloyl Chloride STR25 A slurry of 195.2 g. (0.35 mole) of 5-amino2,4,6-triiodoisophthalic acid in 300 ml. of thionyl chloride was refluxed for 24 hours. During the reflux period the solids dissolved. The solution was cooled to 40 and the solvent evaporated to dryness in vacuum. The gummy residue was dissolved in 250 ml. of tetrahydrofuran and evaporated to dryness. The residue was dissolved in 500 ml. of tetrahydrofuran and washed with a mixture of saturated sodium chloride solution and saturated sodium carbonate. The tetrahydrofuran solution was washed twice with saturated sodium chloride solution and dried over anhydrous calcium chloride. The solution was filtered, diluted with 500 ml. of benzene and evaporated to 450 ml. To this solution 450 ml. of petroleum ether (30-60) was added dropwise with stirring. After standing for 2 hours the solids were isolated and dried to yield 100.5 g. (48%). The material was pure as shown by tlc (silica plate-benzene/acetone 80/20).

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-Amino-2,4,6-triiodoisophthalic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Mallinckrodt, Inc.; US4307072; (1981); A;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Reference of 21304-38-1, 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. 21304-38-1 name is 4-Iodobenzene-1,2-diamine, 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.

4-Iodo-benzene-l,2-diamine was prepared by the literature procedure The diamine was reacted with hexaketocyclohexane octahydrate to give [(HATNA)I3]. The compound is a green colored solid. It is slightly soluble in a mixture of chloroform/TFA.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Iodobenzene-1,2-diamine, and friends who are interested can also refer to it.

Reference:
Patent; GEORGIA TECH RESEARCH CORPORATION; WO2005/123737; (2005); A2;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Reference of 58313-23-8,Some common heterocyclic compound, 58313-23-8, name is Ethyl-3-iodobenzoate, molecular formula is C9H9IO2, 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.

6-(Methyloxy)-3,4-dihydro-l(2H)-isoquinolinone (0.319 g, 1.8 mmol), ethyl-3- iodobenzoate (0.62 niL, 3.68 mmol), copper (I) iodide (0.044g, 0.23 mmol), potassium carbonate (0.247 g, 1.8 mmol) and lambda/,N-dimethylformamide (4 mL) were combined and the stirred reaction mixture was heated at 150 0C under nitrogen for 28 h. The reaction mixture was partitioned between water and ethyl acetate. The layers were separated and the aqueous phase was extracted with ethyl acetate. The organic extracts were combined, dried over magnesium sulfate, filtered, and the filtrate was concentrated to give a gold-yellow liquid. The crude product was purified by flash chromatography over silica with a hexanes:ethyl acetate gradient (100:0 to 50:50) to give 0.32 g (55%) of ethyl 3-[6-(methyloxy)-l-oxo-3,4-dihydro-2(lH)- isoquinolinyl]benzoate as a clear colorless oil. 1H NMR (400 MHz; CDCl3): delta 8.10 (d, J = 9 Hz, IH), 8.00 (s, IH), 7.91 (d, J = 8 Hz, IH), 7.63 (d, J = 8 Hz, IH), 7.46 (t, J = 8 Hz, IH), 6.89 (dd, J = 9, 2 Hz, IH), 6.73 (d, J = 2 Hz, IH), 4.38 (q, J = 7 Hz, 2H), 4.01 (t, J = 6 Hz, 2H), 3.87 (s, 3H), 3.12 (t, J = 6 Hz, 2H), 1.38 (t, J = 7 Hz, 3H). ES- LCMS m/z 326(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 Ethyl-3-iodobenzoate, its application will become more common.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2009/5998; (2009); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Adding a certain compound to certain chemical reactions, such as: 89459-38-1, name is 2-Iodo-4-nitrobenzoic acid, belongs to iodides-buliding-blocks 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 89459-38-1, Application In Synthesis of 2-Iodo-4-nitrobenzoic acid

Step 4: A’-{3-(2-{IM]u0r0met oxy)phenyl)-4,4-d^ A flask was charged with 2-iodo-4-mtrobenzoic acid (i .0 g, 3.41 mmol) in DCM (25 ml,), oxalyl chloride (0.597 mL, 6.83 mmol) and a drop of DMF. After about 20 min the mixture was concentrated under reduced pressure, dissolved in DCM (25 mL) then added to the crude 3-(2-(difluoromethoxy)phenyl)-4,4- dimethoxybutan-1 -amine (3.15 g from step 3, assumed 3.41 mmol) in DCM (25 mL) with TEA (5 mL, 35.9 mmol). The mixture was stirred for about 15 min at rt then water (50 ml.) was added and stirring continued for about 5 min. The solvent layers were separated then the aqueous layer was extracted with DCM (20 mL). The combined organics were washed with saturated sodium bicarbonate (2 x 20 mL) then dried over MgS04, filtered and concentrated under reduced pressure. The material was purified via flash chromatography on silica gel (0-25% EtOAc/DCM). The appropriate fractions were collected and concentrated under reduced pressure to give the title compound (1.23 g, 66%); LC/MS (Table A, Method b) R, – 2.37 min; MS m/z 549 (M-H)”

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; ABBVIE INC.; BREINLINGER, Eric; BURCHAT, Andrew; DIETRICH, Justin; FRIEDMAN, Michael; IHLE, David; KINSMAN, David; MULLEN, Kelly; OSUMA, Augustine; VASUDEVAN, Anil; WILSON, Noel, S.; (101 pag.)WO2016/168638; (2016); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Reference of 3032-81-3, A common heterocyclic compound, 3032-81-3, name is 1,3-Dichloro-5-iodobenzene, molecular formula is C6H3Cl2I, 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.

Preparation of 1,3-dichloro-5-iodo-2-methylbenzene To the mixture of LDA (5 mL, 8.6 mmol) in THF (20 mL) was added compound 1,3-dichloro-5-iodobenzene (2.35 g, 8.6 mmol) under -78° C. Then the mixture was added to the pre-cooled solution of (CH3)2SO4 (12 mL, 10.3 mmol) in THF (10 mL) under -78° C. The solution was concentrated under vacuum. The residue was diluted with EA, washed with 1N HCl, 1N NaOH, brine, dried over Na2SO4, concentrated under vacuum to give the desired product (2.3 g, 93percent yield).

The synthetic route of 3032-81-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Anacor Pharmaceuticals, Inc.; Eli Lilly and Company; Akama, Tsutomu; Balko, Terry William; Defauw, Jean Marie; Plattner, Jacob J.; White, William Hunter; Winkle, Joseph Raymond; Zhang, Yong-Kang; Zhou, Yasheen; US2013/131016; (2013); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

112671-42-8, name is 4-Bromo-1-iodo-2-nitrobenzene, belongs to iodides-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Formula: C6H3BrINO2

(5) Take (100mmol) M4,32.6g (100mmol) of 2-iodo-5-bromonitrobenzene,(1%) Pd (PPh3) 4,40g (300mmol) sodium carbonate,Toluene (800mL),Ethanol (200 mL) and water (200 mL),Heated to reflux, reacted for 8h, the reaction was completed;The reaction solution was extracted with ethyl acetate, and the organic phase was concentrated.A yellow solid M5 was obtained;

The synthetic route of 112671-42-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Yantai Xianhua Chemical Technology Co., Ltd.; Xing Qifeng; Feng Peichuan; Chen Yue; Hu Lingfeng; Chen Yili; (28 pag.)CN110698458; (2020); A;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com