Month: August 2021

These common heterocyclic compound, 518057-72-2, name is 5-Amino-2-fluorobenzamide, 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. category: amides-buliding-blocks

To a solution of 5-amino-2-fluoro-benzamide (0.88 g, 5.7 mmol) and DIEA (3.0 mL, 17 mmol) in THF (20 mL) and dichloromethane (10 mL) at 0 C was added a solution of 6-cyclopropyl-4- [2-methoxy-4-(trifluoromethoxy)phenoxy]pyridine-3-carbonyl chloride (2.1 g, 5.4 mmol) in dichloromethane. The reaction mixture was removed from the ice bath and stirred at room temperature for 1 hour. The reaction mixture was diluted with water and extracted with dichloromethane. The organic layer was concentrated in vacuo and the resulting solid was purified using silica gel chromatography (0-60% ethyl acetate/hexanes) to provide N-(3 -carbamoyl -4-fluoro-phenyl)-6- cyclopropyl-4-[2-methoxy-4-(trifluoromethoxy)phenoxy]pyridine-3-carboxamide (1.1 g, 40%). ESI-MS m/z calc. 505.13, found 506.2 (M+l)+; retention time (Method B): 1.4 minutes (3 minute run). ‘H NMR (400 MHz, DMSO-d6) delta 10.41 (s, 1H), 8.55 (s, 1H), 7.99 (dd, J = 6.5, 2.8 Hz, 1H), 7.87 – 7.76 (m, 1H), 7.69 (d, J = 14.5 Hz, 2H), 7.45 (d, J = 8.8 Hz, 1H), 7.32 – 7.18 (m, 2H), 7.07 (ddd, J = 8.8, 2.8, 1.3 Hz, 1H), 6.59 (s, 1H), 3.80 (s, 3H), 2.07 (p, J = 6.7 Hz, 1H), 0.99 – 0.87 (m, 4H) ppm.

The synthetic route of 5-Amino-2-fluorobenzamide has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; AHMAD, Nadia; ANDERSON, Corey; ARUMUGAM, Vijayalaksmi; ASGIAN, Iuliana, Luci; CAMP, Joanne, Louise; FANNING, Lev Tyler, Dewey; HADIDA RUAH, Sara, Sabina; HURLEY, Dennis; SCHMIDT, Yvonne; SHAW, David; SHETH, Urvi, Jagdishbhai; THOMSON, Stephen, Andrew; (691 pag.)WO2019/14352; (2019); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

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 72179-84-1 as follows. Quality Control of (Methylsulfamoyl)amine

Material from Example 73-Step 1 (40 mg, 0.098 mmol) was dissolved in tetrahydrofuran (5 mL) and 1,1?-carbonyldiimidazole (47.5 mg, 0.293 mmol) was added. The mixture was heated to 60 C for 1 hour, then 1,8-diazabicyclo[5.4.0]undec-7-ene (44.6 mg, 0.293 mmol) and Nmethylsulfuric diamide (32.3 mg, 0.293 mmol) were added followed by stirring at room temperature for 12 hours. The mixture was concentrated, and the residue was dissolved in CH3OH (1.3 mL) to which a couple of drops of acetic acid were added to adjust the pH to 6-7. The filtered solution was purified by preparative HPLC (0.1% CF3CO2H/H20/CH3CN) to give the titled compound (28 mg, 0.056 mmol, 57.1% yield). ?H NMR (400 MHz, DMSO-d6) ppm 11.25 (s, 1H), 7.42 -7.36 (m, 1H),7.33 – 7.08 (m, 4H), 7.06 – 6.96 (m, 2H), 6.86 (d, J = 7.6 Hz, 2H), 3.73 (s, 2H), 3.26 – 3.16 (m, 3H),2.46 (s, 2H), 2.32 – 2.20 (m, 2H), 2.09 (t, J = 7.2 Hz, 1H), 1.73 (s, OH), 1.43 (s, 2H), 1.34 (s, 1H), 1.30- 1.21 (m, 1H), 1.18 (s, 1H), 1.13 (s, 1H), 1.07 (s, 1H), 0.93 (s, 1H).

According to the analysis of related databases, 72179-84-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ABBVIE INC.; BLACK, Lawrence, A.; BUNNELLE, William, H.; CHEN, Da; CLAPHAM, Bruce; DEGOEY, David, A.; DENG, Xiangjun; FU, Liqiang; HAZELWOOD, Lisa, A.; KONG, Linglong; LANG, Qingyu; LEE, Chih-Hung; LI, Mingfeng; LUNDGAARD, Greta, L.; PATEL, Meena, V.; TAO, Ruihong; ZHANG, Lin; ZHANG, Qingwei; ZHENG, Qiangang; ZHU, Wei; (289 pag.)WO2017/177004; (2017); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Related Products of 67442-07-3, A common heterocyclic compound, 67442-07-3, name is 2-Chloro-N-methoxy-N-methylacetamide, molecular formula is C4H8ClNO2, 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 1: 4-bromo-1-chloro-2-fluorobenzene (64 kg) and dry toluene (170 kg) were charged to the 2000 L steel reaction vessel under nitrogen. The reactor was evacuated and backfilled with N2 for three times, and cooled to between -10 and 5° C. under nitrogen atmosphere. To the solution was added dropwise i-PrMgCl.LiCl (280 kg, 1.3M in THF) at between -10 and 10° C. The reaction was stirred for a further 15 to 30 min at between -10 and 10° C. and then warmed to about 20 to 25° C. over 1 h. The reaction mixture was stirred for another 6 h stir to complete the exchange. The resulting solution was cooled to between -50 and -40° C. A solution of 2-chloro-N-methoxy-N-methylacetamide (44.5 kg) in dry toluene (289 kg) was added dropwise to the above solution at while maintaining the temperature between -50 and -30° C. The reaction mixture was warmed to between 20 and 25° C. over 1 h and then stirred for 3 h to complete the reaction. The reaction was quenched by addition of 1N aq. HCl (8081 g) at a temperature between -5 and 15° C. The aqueous layer was separated and organic layer was filtered through a pad of diatomaceous earth. The organic layer was washed with 10percent aq. NaCl solution (320 kg) twice, then concentrated to about 300 L to obtain 1-(4-chloro-3-fluorophenyl)-2-chloroethanone (51.8 kg, 81.9percent yield) as product in toluene.

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; Genentech, Inc.; Lin, Jinguang; Chestakova, Alexandra; Gu, Wei; Iding, Hans; Li, Jing; Linghu, Xin; Meier, Patrik; Sha, Chunbo; Stults, Jeffrey; Wang, Youchu; Zhang, Haiming; Zhang, Jianqian; Zhang, Tao; (56 pag.)US2017/22183; (2017); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Application of 6312-87-4, These common heterocyclic compound, 6312-87-4, name is N-(4-Phenoxyphenyl)acetamide, 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: Dimethylformamide (3 mmol) was added to N-phenylacetamides(2a-2g, 1 mmol) in an ice bath, then phosphoryl chloride(15 mmol) was added dropwise to the mixture and was stirredat ice bath for 20 min, then the reaction proceeded at temperature80e90 C for 7e10 h. After completion of the reaction, ice is addedto the mixture and was stirred, then the formed precipitate wasfiltrated and recrystallized in ethanol [31]. Compounds 3a, 3c, 3d, 3f and 6a were reported in the literatures[32e35].2.3.1. 2-Chloro-6-phenoxyquinoline-3-carbaldehyde (3b)Yellow solid; yield: 61%; mp: 110e113 C; 1H NMR (300 MHz-CDCl3) d 7.18e7.20 (d, 2H, J 6 Hz, AreH), 7.26e7.30 (t, 1H, J 6 Hz,AreH), 7.47e7.53 (m, 2H, AreH), 7.75e7.79 (m, 2H, AreH),8.08e8.11 (d, 1H, J 9 Hz, AreH), 8.92 (s, 1H, AreH), 10.37 (s, 1H,CHO).

The synthetic route of 6312-87-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Mirzaei, Salimeh; Hadizadeh, Farzin; Eisvand, Farhad; Mosaffa, Fatemeh; Ghodsi, Razieh; Journal of Molecular Structure; vol. 1202; (2020);,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Application of 98-18-0, 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. 98-18-0, name is 3-Aminobenzenesulfonamide belongs to amides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

A solution of 3-aminobenzenesulfonamide (413.3 mg, 2.40 mmol), 2,5- difluoro-4-methyl-benzoic acid (344.3 mg, 2.0 mmol), HATU (684.4 mg, 1.80 mmol) and N- methylmorpholine (439.8 mu, 4.0 mmol) in DMF (2 mL) was stirred at 40 °C for 2 hours. The reaction was poured into IN HCl and extracted with ethyl acetate (3x). The organics were combined, washed with water, brine, dried with Na2S04 and evaporated to dryness to give 2,5-difluoro-4-methyl-N-(3-sulfamoylphenyl)benzamide (610 mg, 94percent) as a solid that was used in the next step without further purification. ESI-MS m/z calc. 326.05, found 327.3 (M+1) +; Retention time: 1.25 minutes (3 minutes run).

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

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; HADIDA-RUAH, Sara Sabina; ANDERSON, Corey; TERMIN, Andreas P.; BEAR, Brian Richard; ARUMUGAM, Vijayalaksmi; KRENITSKY, Paul; JOHNSON, James Philip; WO2015/10065; (2015); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

3144-09-0, name is Methylsulfonamide, belongs to amides-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. Quality Control of Methylsulfonamide

A mixture of 4-bromobenzaldehyde (0.250 g, 1.40 mmol), methanesulfonamide (0.154 g, 1.62 mmol), copper iodide (0.0510 g, 0.270 mmol), N,N-dimethylglycine (0.0280 g, 0.270 mmol), and potassium phosphate tribasic (0.716 g, 3.38 mmol) in DMF (5.00 mL) was stirred at reflux for 16 hours. The mixture was diluted with EtOAc (50 mL), washed with water (50 mL), and then saturated aqueous LiCl (5 mL). The combined aqueous layers were then back-extracted with EtOAc (50 mL). The organic layers were combined, washed with brine (50 mL), dried over Na2SO4, filtered, and the solvent was removed under reduced pressure, to provide N-(4-formylphenyl)methanesulfonamide (0.161 g, 58%) as a yellow oil

The synthetic route of 3144-09-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; RVX Therapeutics Inc.; McLure, Kevin G.; Young, Peter R.; US2013/281399; (2013); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Reference of 340187-12-4, These common heterocyclic compound, 340187-12-4, name is (9H-Fluoren-9-yl)methyl (2-bromoethyl)carbamate, 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.

A mixture of Example 123 (21 mg, 0.05 mmol), (9H-fluoren-9-yl)methyl2- bromoethylcarbamate (36 mg, 0.1 mmol) and K2CO3 (20 mg, 0.15 mmol) in DMF (1 mL) was stirred stirred at rt overnight. Piperidine (0.5 mL) was added and the mixture was stirred for another hour. The reaction mixture was purified by etaPLC to afford the product as a white solid. 1H-NMR (400 MHz, CD3CN) delta = 7.97 (br s, 2H), 7.04 (d, J = 8.1 Hz, IH), 6.76 (dd, J = 2.8, 8.4 Hz, IH), 6.72 (d, J = 2.4 Hz, IH), 4.75 (t, J = 5.6 Hz, 2H), 4.31 (s, 2H), 4.02 (m, 2H), 3.95 (t, J = 6.4 Hz, 2H), 3.49 (t, J = 5.6 Hz, 2H), 3.45 (t, 7 = 6.0 Hz, 2H), 2.93-2.86 (m, 4H), 2.80 (s, 3H), 1.80-1.76 (m, 4H), 1.53 (m, IH), 1.43- 1.38 (m, 2H), 1.24 (ddd, J = 4.0, 12.4, 24.2 Hz, 2H); MS calcd. for [M+H]+ C2iH34N7O3S: 464.2; found: 464.2.

The synthetic route of 340187-12-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; IRM LLC; WO2008/97428; (2008); A2;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Synthetic Route of 148017-28-1, A common heterocyclic compound, 148017-28-1, name is tert-Butyl sulfamoylcarbamate, molecular formula is C5H12N2O4S, 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.

b) Preparation of a sulfamide compound To a solution of (2R,4S)-4-acetylthio-1-t-butoxycarbonylpyrrolidine-2-methanol (i.e., a substrate) in tetrahydrofuran (THF), triphenylphosphine (PPh3), N-t-butoxycarbonylsulfamide (BSMD), and azodicarboxylic acid diethyl ester (DEAD) are successively added under ice cooling. The conditions for this reaction are shown in Table 2, Step A-6. The reaction mixture is diluted with toluene, concentrated, diluted with toluene, and the formed crystals are filtered off. The filtrate is concentrated. The residue is purified by silica gel column chromatography to give (2R,4S)-4-acetylthio-1-t-butoxycarbonyl-2-(N-t-butoxycarbonyl-N-sulfamoylamino)methylpyrrolidine. NMR delta(CDCl3) ppm: 1.41(s, 9H), 1.55(s, 9H), 1.19 to 2.0(m, 2H), 2.35(s, 3H), 3.32(dd, J=11.4 Hz, J=8.2 Hz, 1H), 3.6 to 3.9(m, 3H), 3.9 to 4.1(m, 1H), 4.5(m, 1H), 6.15(s, 2H). IR nu (KBr) cm-1: 3420, 3320, 1706, 1686, 1666.

The synthetic route of 148017-28-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shionogi Seiyaku Kabushiki Kaisha; US5317016; (1994); A;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 18469-37-9, name is 4-Bromo-N,N-dimethylbenzamide, belongs to amides-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 18469-37-9, SDS of cas: 18469-37-9

N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0243) To a solution of 4-bromo-N,N-dimethylbenzamide (11.0 g, 48.23 mmol) in dioxane (300 mL) were added 4,4,5,5-tetramethyl-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (14.7 g, 57.89 mmol), Pd(dppf)Cl2 (3.5 g, 4.78 mmol) and potassium acetate (14.2 g, 144.69 mmol) at room temperature. The resulting mixture was stirred for 16 h at 100 C. The reaction mixture was cooled to room temperature and the resulting solid was removed by filtration. The filtrate was concentrated under reduced pressure and the resulting residue was purified by flash chromatography eluting with EtOAc in hexane (0% to 40% gradient) to yield N,N-dimethyl-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide as orange solid (10.0 g, 70%). MS: m/z=276.0 [M+H]+.

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

Reference:
Patent; Merck Patent GmbH; SHERER, Brian A.; KARRA, Srinivasa; XIAO, Yufang; (407 pag.)US2016/376283; (2016); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

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. 579-10-2, name is N-Methylacetanilide, This compound has unique chemical properties. The synthetic route is as follows., category: amides-buliding-blocks

A solution of N-methyl-N-phenylacetamide (73.8 mmol) in dichloromethane (20 mL) was added dropwise to sulfurochloridic acid (690 mmol) at 5 C. and the resulting solution was allowed to warm to rt and was maintained 16 h. The reaction mixture was diluted with iced water (100 mL) and was extracted with dichloromethane (2×50 mL). The combined organic layers were dried (sodium sulfate) and concentrated. The residue was purified by Flash chromatography (10/1 ethyl acetate/petroleum ether) to give 4-(N-methylacetamido)benzene-1-sulfonyl chloride in 11% yield as a white solid. 1H NMR (CDCl3) delta 8.09 (d, 2H), 7.48 (d, 2H), 3.38 (s, 3H), 2.17 (s, 3H).

According to the analysis of related databases, 579-10-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Memory Pharmaceuticals Corporation; US2010/29629; (2010); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics