Month: December 2020

Application of 7341-96-0, A common heterocyclic compound, 7341-96-0, name is Propiolamide, molecular formula is C3H3NO, 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 solution of 4-(tert-butyl-dimethyl-silanyloxymethyl)-benzaldehyde oxime (which may be made as described in Preparation of Intermediate 17; 3 g, 11.3 mmol) in DMF (25 mL) was cooled to 0 C and N-chlorosuccinimide (1.51 g, 11.3 mmol) was added in portions. The cooling bath was removed and the reaction mixture was stirred for 2.5 h. The mixture was poured into ice- water (75 mL) and this was extracted with Et2O (3 x 100 mL). The combined organic layers were washed with brine, dried (Na2SO4) and evaporated to give a solid (3.5 g). The solid was dissolved in 50% aqueous tert-butanol (60 mL) in a flask that was open to the air. Propiolamide (which may be prepared as described in Matsumoto, T. et al. US 7,851,473 Column 128; 0.7 mL, 6.85 mmol) was added, followed by 1 M sodium ascorbate (1.13 mL, 1.13 mmol) and 0.1 M copper(II) sulfate (5.65 mL, 0.565 mmol). KHCO3 (4.52 g, 45.1 mmol) was added in portions and the reaction mixture was stirred at room temperature for 2.5 h. H2O (100 mL) was added and a yellow solid was filtered off and dried under high vacuum overnight (3 g). This material was taken up in CH2Cl2/acetone and filtered. The filtrate was evaporated and the residue was purified by chromatography (9-20% acetone/CH2Cl2) to give 3-[4-(tert-butyl-dimethyl- silanyloxymethyl)-phenyl]-isoxazole-5-carboxylic acid amide (800 mg, 21%). Purification of mixed fractions by chromatography (50-60% EtO Ac/toluene) provided a further 450 mg (12%) of 3-[4-(tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-isoxazole-5-carboxylic acid amide.

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; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; ERICKSON, Shawn, David; GILLESPIE, Paul; MERTZ, Eric; WO2014/86704; (2014); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

5466-88-6, 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. 5466-88-6 name is 2H-1,4-Benzoxazin-3(4H)-one, 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.

2. Synthesis of 3-oxo-3,4-dihydro-2H-benzo[b’||’l,4]oxazine-6-sulfonyl chloride.2H-Benzo[b][l,4]oxazin-3(4H)-one (13.4 mmol) was added in several batches over 20 min to sulfurochloridic acid (10 mL) at 0 0C and the reaction mixture was maintained for 1 h. The reaction mixture was cautiously poured into ice (100 g) and the resulting mixture was extracted with dichloromethane (100 mL). The organic layer was dried (sodium sulfate) and concentrated to provide 3-oxo-3,4-dihydro-2H-benzo[b][l,4]oxazine-6-sulfonyl chloride in 66% yield as a white solid. Data: 1HNMR (400MHz, CDC13) delta 9.29 (s, IH), 7.71 (d, 2H), 7.52 (s, IH), 7.16 (d, 2H), 4.80 (s, 2H). LC/MS (ES) m/z 317 [M+BnNH-H].

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2H-1,4-Benzoxazin-3(4H)-one, and friends who are interested can also refer to it.

Reference:
Patent; MEMORY PHARMACEUTICALS CORPORATION; DANCA, Mihaela, Diana; DUNN, Robert; TEHIM, Ashok; XIE, Wenge; WO2010/21797; (2010); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

1882-71-9, The chemical industry reduces the impact on the environment during synthesis 1882-71-9, name is 2-Amino-5-methoxybenzamide, I believe this compound will play a more active role in future production and life.

General procedure: A mixture of 2-aminobenzamide (1, 4.0 mmol), carboxamide (2, 6.0 mmol), Yb(OTf)3 (0.20 mmol,5.0 molpercent), and mesitylene (5.0 mL) was placed in a 20-mL Pyrex flask equipped with a magnetic stirring bar and a reflux condenser under a flow of argon. The reaction was carried out at 120-165 oC (bath temp.) for 6 h with stirring. Then, the reaction mixture was cooled to room temperature, and analyzed by GLC, GC-MS (EI), and LC-MS (ESI). After evaporation of mesitylene under vacuum,the products (3) were isolated by recrystallization from MeOH/hexane and/or medium pressure column chromatography on silica gel (eluent: EtOAc/hexane = 50/50 ~ EtOAc 100percent. For 3j, eluent:MeOH/CHCl3 = 50/50). 1H NMR spectra were recorded at 400 MHz, and 13C NMR spectra wererecorded at 100 MHz in DMSO-d6. The analytical and spectral data of 3a-e,38 3f,39 3g,40 3h,41 and3j,42 were consistent with those reported previously. The product, 3i, was characterized below.

The chemical industry reduces the impact on the environment during synthesis 2-Amino-5-methoxybenzamide. I believe this compound will play a more active role in future production and life.

Reference:
Article; Yoshimura, Tsutomu; Yuanjun, Di; Kimura, Yu; Yamada, Hisatsugu; Toshimitsu, Akio; Kondo, Teruyuki; Heterocycles; vol. 90; 2; (2015); p. 857 – 865;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

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. 148017-28-1, name is tert-Butyl sulfamoylcarbamate, A new synthetic method of this compound is introduced below., 148017-28-1

Example 16 N-(4-{4-[3-(2-sulfamoylaminoethoxy)azetidin-1-yl]phenylamino}-6-methoxypyridin-3-yl)acetamide (16a) N-(4-{4-[3-(2-tert-butoxycarbonylsulfamoylaminoethoxy)azetidin-1-yl]phenylamino}-6-methoxypyridin-3-yl)acetamide N-(4-{4-[3-(2-Hydroxyethoxy)azetidin-1-yl]phenylamino}-6-methoxypyridin-3-yl)acetamide (850 mg, 2.28 mmol) produced in Example 1 (1f), N-tert-butoxycarbonylsulfamoyl amine (0.67 g, 3.4 mmol), and triphenylphosphine (0.72 g, 2.7 mmol) were suspended in ethyl acetate:tetrahydrofuran (3:1, 15 mL), diethyl azodicarboxylate (0.74 mL, 3.4 mmol) was added, and the mixture was stirred at room temperature for 20 hr. The solvent of the reaction mixture was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform:methanol, 100:0?100:4, V/V). The solvent of the object fraction was evaporated under reduced pressure to give the title object compound as a pale-yellow foam-like powder (1.05 g, yield 84%). 1H-NMR (CDCl3, 400 MHz) delta: 1.55 (9H, s), 1.96 (1H, s), 2.24 (2H, s), 3.61 (2H, t, J=5.3 Hz), 3.66-3.74 (2H, m), 3.82 (2H, s), 3.85 (1H, s), 3.98 (2H, t, J=5.3 Hz), 4.00-4.08 (2H, m), 4.38-4.46 (1H, m), 5.44-5.55 (2H, br), 6.10 (0.35H, s), 6.12 (0.35H, s), 6.15 (0.65H, s), 6.34 (0.65H, s), 6.41-6.50 (2H, m), 6.54 (0.65H, s), 6.98-7.07 (2.35H, m), 7.78 (0.65H, s), 7.79 (0.35H, s).

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; Kyoto Pharmaceutical Industries, Ltd.; SHIRAHASE, Hiroaki; TAKAHASHI, Kenji; SHOJI, Yoshimichi; TAKEDA, Shigemitsu; (111 pag.)US2016/207883; (2016); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

869494-16-6, 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. 869494-16-6, name is tert-Butyl 3,6-diazabicyclo[3.1.1]heptane-6-carboxylate belongs to amides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

(5-Amino-1-[4-(2-fluorophenoxy)-2-methylphenyl]pyrazol-4-yl}-[6-bromo-5-(2-bromoethoxy)-1H-indol-2-yl]methanone (100 mg) was suspended in acetonitrile (1.0 mL), tert-butyl 3,6-diazabicyclo[3.1.1]heptane-6-carboxylate (63 mg) and cesium carbonate (130 mg) were added, and the mixture was stirred at 70¡ãC for three hours. Water was added to the reaction solution, the mixture was extracted with ethyl acetate, and the organic layer was dried over sodium sulfate. After removing the drying agent by filtration, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by column chromatography (hexane/ethyl acetate) to give the target compound (79 mg).

The synthetic route of 869494-16-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Chugai Seiyaku Kabushiki Kaisha; F. Hoffmann-La Roche AG; EBIIKE, Hirosato; AOKI, Toshihiro; CHIBA, Takashi; KOCHI, Masami; NAKAMA, Kimitaka; NIIZUMA, Satoshi; NISHII, Hiroki; OHWADA, Jun; SHIMAMURA, Hiroyuki; SUGE, Aiko; NAKANISHI, Yoshito; KOBAYASHI, Natsuki; (594 pag.)EP3312172; (2018); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

A common heterocyclic compound, 88-96-0, name is Phthalamide, molecular formula is C8H8N2O2, 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. 88-96-0.

Example 20B (404 mg, 1.13 mmol), triphenylphosphine (455 mg, 1.6 eq.) and phthalamide (222 mg, 1.4 eq.) were mixed in 3.5 mL of toluene. Then, di-tert-butylazodicarboxylate (DBAD, 398 mg, 1.6 eq.) was added. The reaction flask was flushed with argon and then heated to 90 C. After stirring overnight at 90 C., the mixture was cooled to room temperature, concentrated and the resulting oil was purified by column chromatography (eluding with 20% to 40% ethyl acetate in hexane) to give the title compound (684 mg).

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

Reference:
Patent; Pei, Zhonghua; Geldern, Thomas von; Madar, David J.; Li, Xiaofeng; Basha, Fatima; Yong, Hong; Longenecker, Kenton L.; Backes, Bradley J.; Judd, Andrew S.; Mulhern, Matthew M.; Stewart, Kent D.; US2007/49596; (2007); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

191170-76-0, The chemical industry reduces the impact on the environment during synthesis 191170-76-0, name is Benzyl 4-bromophenethylcarbamate, I believe this compound will play a more active role in future production and life.

A solution of H2SO4 (3 ml) and AcOH (6 mL) was cooled in an ice bath for 10 min. Paraformaldehyde (1.00 g, 33.3 mmol) and benzyl (4-bromophenethyl)carbamate (0.92 g, 2.75 mmol) were added to the cooled solution and the reaction was stirred for 10 min at 0 C, where upon the reaction was poured onto ice (ca. 50 g). When the ice melted, the aqueous solution was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with a saturated aqueous solution of NaHCCb (1 x 50 mL), water (1 x 50 mL), and brine (1 x 50 mL). The organic layer was dried (Na2S04) and concentrated under reduced pressure. The crude material was purified via flash column chromatography eluting with EtOAc:hexanes (5:95) to give 720 mg (76%) of title co s consistent with literature.1

The chemical industry reduces the impact on the environment during synthesis Benzyl 4-bromophenethylcarbamate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM; MARTIN, Stephen, F.; SAHN, James, J.; LINKENS, Kathryn, Taylor; (119 pag.)WO2017/190109; (2017); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

89979-12-4, 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 89979-12-4 as follows.

Example 12 Preparation of Intermediate 11 [0467] [0468] HATU (1.37 g, 3.59 mmol) was added to a solution of 5-chloro-2-(methylsulfonamido)benzoic acid (823 mg, 3.29 mmol) in DMF (15.0 mL), and the reaction mixture was stirred at room temperature. After 1 h, a solution of crude intermediate 6 (220 mg, 2.99 mmol) in DMF (1 mL) was added followed by the addition of triethylamine (2.00 mL, 14.3 mmol), and the reaction mixture was stirred at room temperature for 19 h. The reaction mixture was partitioned between ethyl acetate (250 mL) and saturated aqueous sodium bicarbonate solution (200 mL), and the layers were separated. The organic layer was washed with saturated aqueous sodium bicarbonate solution (200 mL) and saturated sodium chloride solution (200 mL), was dried over Na2SO4, and was concentrated under reduced pressure. The crude residue was purified via SiO2 column chromatography (12 g SiO2 Combiflash HP Gold Column, 0-100% ethyl acetate/hexanes) to afford intermediate 11 (736.2 mg, 51% (2-steps)) as a white solid. [0469] 1H NMR (CDCl3, 400 MHz): delta 10.05 (br s, 0.2H), 9.13 (br s, 1H), 8.95 (br s, 1H), 8.81 (br s, 0.2H), 7.70 (d, J=8.8 Hz, 1H), 7.56 (d, J=8.8 Hz, 0.2H), 7.40 (dd, J=8.8, 2.4 Hz, 1H), 7.33 (d, J=2.4 Hz, 1H), 7.31 (d, J=4.4 Hz, 0.2H), 6.45 (s, 1H), 6.40 (br s, 0.2H), 6.28 (br d, J=4.4 Hz, 1H), 5.01 (br s, 0.2H), 4.54 (br d, J=14.0 Hz, 0.2H), 3.35 (br d, J=13.2 Hz, 1H), 3.15-3.03 (m, 1H), 2.92 (s, 3H), 2.39 (s, 3H), 2.13-1.98 (m, 1H), 1.90-1.59 (m, 2H), 1.59-1.31 (m, 3H). [0470] 13C NMR (CDCl3, 100 MHz): delta 167.09, 156.12, 153.13, 147.86, 135.68, 131.79, 131.66, 131.38, 130.12, 125.91, 125.44, 117.08, 93.74, 47.65, 44.07, 39.81, 27.83, 25.47, 19.78, 16.90. [0471] LCMS (ESI) m/z 482.1 [M+H]+, tR=2.79 min. [0472] HPLC tR (min), purity %: 5.438, 99% [0473] Rf=0.47 (50% EtOAc/hexanes). [0474] Chiral HPLC, 99% ee (Chiralpak IC 5 mM, 4.6¡Á150 mm, 10-95% MeCN/H2O, 0.05% trifluoroacetic acid modifier) (S)-isomer tR=29.739 min, (R)-isomer tR=29.495 min.

According to the analysis of related databases, 5-Chloro-2-(methylsulfonamido)benzoic acid, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Siegel, Dustin; Sperandio, David; Yang, Hai; Sangi, Michael; Parrish, Jay P.; Hui, Hon Chung; US2013/273037; (2013); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

749927-69-3, Adding a certain compound to certain chemical reactions, such as: 749927-69-3, name is 4-Bromo-2-fluoro-N-methylbenzamide, 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 749927-69-3.

100 ml of DMF was added to a 250 ml three-necked flask,A solution of 18.5 g of 5,5-dimethyl-3- (3-trifluoromethyl-4-fluorophenyl) -2-thiamidazol-4-one was successively added with stirring,Ice bath cooling to 0-5 C,Add 3.9 g of sodium hydride in portions.Plus,The ice bath continues to stir for 30 min.13.68 g of 2-fluoro-4-bromobenzoylmethylamine was dissolved in 30 ml of DMF,Slowly add it toIn the reaction solution, control the internal temperature 0-5 C.Plus finished, returned to room temperature, continue to stir 5h,TLC monitoring reaction is completed.The reaction solution was addedTo 500 ml of water, filtered to obtain crude.After drying, column chromatography was performed to obtain 23.9 g of enterine, the yield was 87.3%.

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, 4-Bromo-2-fluoro-N-methylbenzamide, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Chengdu Yinuo Dabo Pharmaceutical Technology Co., Ltd.; Fu Qingquan; Yue Lijian; Lin Qiang; Liao Xianbo; Zhao Maoxian; Qin Yan; (8 pag.)CN104844520; (2017); B;,
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. 121492-06-6, name is N-Boc-(2-Aminoethyl)-N-methylamine, This compound has unique chemical properties. The synthetic route is as follows., 121492-06-6

General procedure: 5-Amino-(30-[N0-methyl-N0-tert-butoxycarbonyl]propyl)-3-(N,N-dimethylcarbox-amide)-6-nitrochromane (9a).[29]A mixture of 5-chloro-3-N,N-dimethyl-carboxamide-6-nitro-chromane (8) (300 mg, 1.10 mmol), primary amine N-Boc-N-methyl-1,3-trimethylenediamine (18) (5.50 mmol),and N-methyl-pyrrolidinone (1.0 mL) was heated in a sealedtube at 758C for 48 h. The reaction mixture was poured into amixture of diethyl ether and water (1 : 1, 80 mL) and the mixturestirred for 30 min. The mixture was transferred to a separationfunnel and the ether layer washed with water (4 25 mL). Theorganic phase was dried over anhydrous sodium sulfate, filtered,and evaporated under reduced pressure. The crude product waspurified by flash chromatography (silica gel, 5 % methanol indichloromethane). The product 9a[29]was isolated as a brightyellow oil (381 mg, 87 %).

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:
Article; Schmit, David; Milewicz, Urszula; Boerneke, Mark A.; Burley, Scott; Walsworth, Kevin; Um, Joann; Hecht, David; Hermann, Thomas; Bergdahl, B. Mikael; Australian Journal of Chemistry; (2020);,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics