Category: amides-buliding-blocks

Application of 25625-57-4,Some common heterocyclic compound, 25625-57-4, name is 2-Bromo-N-(3-(trifluoromethyl)phenyl)acetamide, molecular formula is C9H7BrF3NO, 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 10a Chiral isomer 12-{3-[4-(4-methyl-1 H-imidazol-1 -yl)phenyl]-2-oxo-7-oxa-1 ,4-diazaspiro[4.5]dec-3-en-1 -yl}-N-[3-(trifluoromethyl)phenyl]acetamide hydrochloride 3-[4-(4-Methyl-1 H-imidazol-1 -yl)phenyl]-7-oxa-1 ,4-diazaspiro[4.5]dec-3-en-2-one (D31 a), isomer 1 (94mg) in DMF (6ml) was cooled to ice bath temp and treated with sodium hydride 60% in oil (13mg) under an atmosphere of argon. The mixture was stirred for 20 minutes when 2-bromo-N-[3-(trifluoromethyl)phenyl]acetamide (85mg) in DMF (2.5ml) was added over 1.5 hours by syringe pump. The mixture was then allowed to warm to room temp overnight. The solvent was partially removed and the residue was purified by low pH MDAP. The fractions were loaded onto SCX and the free base was eluted with 2M methanolic ammonia. The solvent was removed and the residue was dissolved in DCM, treated with HCI-Et2O, solvent removed and a white solid was obtained from ether (78mg).1H NMR (DMSO) delta: 1.75 (2H, m), 2.05-2.35 (obs, m), 2.45 (3H, s), 3.4-3.6 (obs, m), 3.9 (2H, m), 4.98 (2H, m), 7.45 (1 H, m), 7.58 (1 H, m), 7.75 (1 H, m), 7.98 (2H, m), 8.12 (2H, m), 8.58 (2H, m), 9.63 (1 H, s), 10.74 (1 H, s). 19F NMR (DMSO) delta: 61.4 Mass Spectrum (LC/MS): Found 512 (MH+). Ret. time 1.63 min.Example 10b Chiral isomer 2 2-{3-[4-(4-methyl-1 H-imidazol-1 -yl)phenyl]-2-oxo-7-oxa-1 ,4-diazaspiro[4.5]dec-3-en- 1-yl}-N-[3-(trifluoromethyl)phenyl]acetamide-‘J 3-[4-(4-Methyl-1 H-imidazol-1 -yl)phenyl]-7-oxa-1 ,4-diazaspiro[4.5]dec-3-en-2-one (D31 b), isomer 2 (94mg) in DMF (6ml) was cooled to ice bath temp and treated with sodium hydride 60% in oil (12mg) under an atmosphere of argon. The mixture was stirred for 20 minutes when 2-bromo-N-[3-(trifluoromethyl)phenyl]acetamide (85mg) in DMF (2.5ml) was added over 1.5 hours by syringe pump. The mixture was then allowed to warm to room temp overnight. The mixture was poured into water and extracted with dichloromethane. The organic layer was washed with brine and then dried with hydromatrix and the solvent was removed to give the title compound (104mg). 1H NMR (CDCI3) delta: 1.7 (obs, m), 2.0 (2H, m), 2.15-2.4 (2H, m), 3.31 (3H, m), 3.71 (1 H, m), 3.85 (2H, m), 4.05 (1 H, m), 4.45 (2H, m), 7.10 (1 H, s), 7.3-7.5 (4H, m), 7.68 (1 H, m), 7.84 (1 H, m), 7.94 (1 H, m), 8.60 (2H, m), 9.09 (1 H, s). 19F NMR (DMSO) delta: 62.7 Mass Spectrum (LC/MS): Found 512 (MH+). Ret. time 1.62 min.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-N-(3-(trifluoromethyl)phenyl)acetamide, its application will become more common.

Reference:
Patent; GLAXO GROUP LIMITED; WO2009/34061; (2009); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Electric Literature of 7160-22-7,Some common heterocyclic compound, 7160-22-7, name is N-(3,4-Dichlorophenyl)pivalamide, molecular formula is C11H13Cl2NO, 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.

N-(3,4-dichlorophenyl)-2,2-dimethylpropanamide (121 g) was dissolved in 720 mL THF and the solution was cooled to -50 0C. Butyllithium (433 mL, 2.5N in hex) was added while keeping the internal temperature between -45 0C and -35 0C. (final temp.: -35 0C) and held at -25 0C for 40 min. An hplc check of the reaction mixture revealed that 5-10 % of the starting material remained. An additional 25 mL of butyllithium was added at -30 0C and the reaction was at -30 to – 25 0C for a further 30 min (HPLC: no significant change). The reaction mixture was cooled to -45 0C and SO2 was bubbled though the solution until saturation appeared to have been reached. Subsequently, the reaction mixture was at – 10 to 0 0C for 45 min. Argon (2 double -balloon volumes) was bubbled through the solution following which the reaction mixture was cooled to -5 0C. Sulfuryl chloride (58.8 mL) was added while keeping the temperature below 22 0C. The reaction mixture was kept at 10-15 0C for 1 h (HPLC: complete). EtOAc was added and the mixture was concentrated, washed with water, saturated aqueous sodium bicarbonate and brine, dried over MgStheta4 and the solvent was evaporated in vacuo. The crude material crystallized and was triturated with hot hexane. Yield: 87.2 g 1H-NMR (DMSOd6) delta 7.60(d, J= 8.4Hz, IH), 7.34(d, J= 8.4Hz, IH), 1.43(9H, s).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route N-(3,4-Dichlorophenyl)pivalamide, its application will become more common.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2007/124423; (2007); A2;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 513-74-6, name is Ammonium carbamodithioate, 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 513-74-6, HPLC of Formula: CH6N2S2

Step 89.2: Ammonium dithiocarbamate (208 mg, 1.89 mmol) and 72 (X = Br) (200 mg, 0.63 mmol) in anhydrous MeOH (10 mL) was stirred for 10 mins. The resulting cream precipitate was collected by filtration, resuspended in acetic acid (10 mL) and refluxed for 1 hr. The reaction was cooled to room temperature and diluted with ice cold water. The resulting green precipitate was collected by filtration, redissolved in (CH2CI2:Me0H 95:5, 100 mL) and dried (Na2SO4). The pale green solution was concentrated in vacuo to give 4-(5-bromopyrazolo[1 ,5-a]pyridin-3-yl)thiazole-2(3/-/)-thione (73: X = Br) (136 mg, 70 percent) that is stored in the freezer. 1H NMR delta (400 MHz, d6-DMSO) 13.59 (br s, 1 H), 8.74 (d, J 7.3 Hz, 1H1), 8.51 ( s, 1 H ), 8.22 (d, J 1.8 Hz, 1H), 7.27 (s, 1 H1), 7.19 (dd, J 7.3, 2.1 Hz, 1 H). LCMS (APCI+) 312 (MH+ with 79Br, 100percent), 314 (MH+ with 81Br, 100percent).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ammonium carbamodithioate, and friends who are interested can also refer to it.

Reference:
Patent; AUCKLAND UNISERVICES LIMITED; WO2009/8748; (2009); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Reference of 915087-25-1, The chemical industry reduces the impact on the environment during synthesis 915087-25-1, name is 4-Amino-2-fluoro-N-methylbenzamide, I believe this compound will play a more active role in future production and life.

Synthesis of 3,5-dideutero-4-amino-2-fluoro-N-methyl benzamide (compound 22) Into a suspension of compound 5 (1 g, 5.95 mmol) in heavy water (10 mL) concentrated hydrochloric acid (0.5 mL, 6.00 mmol) was added, thereby forming the heavy water solution of the hydrochloride salt of compound 5. The mixture was heated to 125 C. by microwave, and reacted for 30 min. Then the reaction solution was adjusted to alkaline with 1 M NaOH aqueous solution, and white solid precipitated. The solid was filtered and washed with water (20 mL*3), dried in an oven to give compound 22 as a white solid (0.80 g, 79.0% yield). 1H NMR (CDCl3, 400 MHz): delta (ppm) 7.92 (1H, d, J=8.8 Hz), 6.62 (1H, s), 4.10 (2H, s), 2.99 (3H, s).

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

Reference:
Patent; HC PHARMACEUTICAL CO., LTD.; Chen, Yuanwei; US2014/371284; (2014); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Application of 104060-23-3, 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. 104060-23-3 name is N-Boc-2-(4-Aminophenyl)ethanol, 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.

This compound (1.5 g, 8.6 mmol) was suspended in dry tetrahydrofuran (20 mL) at EPO 250C. The 4-(N-l-terf-butyloxycarbonyl)-aminophenethyl alcohol (3.4 g, 14.5 mmol) and triphenylphosphine (3.8 g, 14.5 mmol) were then added, and the mixture evaporated to dryness. Dry tetrahydrofuran (20 mL) was added and the suspension was cooled to 0C before dropwise addition of diethylazodicarboxylate (1.5 mL, 9.8 mmol). After 16 h reaction at room temperature, the solution was concentrated under reduced pressure. The crude residue was purified on a BIOTAGE 25M column (silica, hexane/AcOEt 95:5 to 75:25) to yield N-9 alkylated purine as a white solid (2.9 g, 87%). To a solution of alkylated 2-fluoro-6-chloropurine (3.0 g, 7.7 mmol) in n- butanol (15 mL) at 250C was added N- 1-tert-butyloxycarbonyl- 1,3 -phenyl enediamine (1.8 g, 8.8 mmol) and diisopropylethylamine (2.7 mL, 15.3 mmol). After 48 h reaction at 65C, the brown solution was concentrated under reduced pressure. The crude residue was purified on a BIOTAGE 4OM column (silica, hexane/ AcOEt 65:45 to 0:1) to yield the fluoropurine derivative as a brown solid (2.8 g, 63%). To a solution of this product (2.8 g, 4.9 mmol) in n-butanol (15 mL) at room temperature was added aminomethylcyclopropane (1.2 g, 17.1 mmol) and diisopropylethylamine (1.7 mL, 9.8 mmol). After 48 h reaction at 1100C, the brown solution was concentrated under reduced pressure. The crude residue was purified on a BIOTAGE 4OM column (silica, hexane/ AcOEt 60:40 to AcOEt/MeOH 98:2) to yield the protected trisubstituted purine as a white solid (2.3 g, 73%). To a solution of this compound (2.08 g, 3.38 mmol) in dichloromethane (10 mL) at room temperature was added 4N HCl in dioxane (10 mL). The reaction was stirred for 5 h at 25C and the solution was concentrated under reduced pressure. The solid was then dried for 16 h under vacuum to yield compound 3 as a brown solid. Yield of product: 1.4 g (quantitative); Rf = 0.1 (CH2Cl2/Me0H 98:2); 1H NMR (400 MHz, CD3OD): delta 8.24 (s, IH), 8.20-7.60 (m, 2H), 7.60-7.00 (m, 6H), 4.56 (t, 2H, J= 7.0 Hz), 3.40-3.20 (m, 4H), 1.25-1.15 (m, IH), 0.60-0.50 (m, 2H), 0.40-0.20 (m, 2H); LRMS (ESI): m/z 415 (MH+), 437 (M+ Na); HPLC (method 2): 1.6 min.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, N-Boc-2-(4-Aminophenyl)ethanol, and friends who are interested can also refer to it.

Reference:
Patent; PROMETIC BIOSCIENCES INC.; WO2006/136005; (2006); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 142-26-7, name is N-Acetylethanolamine, 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 142-26-7, Recommanded Product: N-Acetylethanolamine

EXAMPLE 11 2-(Acetylamino)-9(Z)-octadecenoate, 15 To a solution of 1.0 g of oleoyl chloride in 10 ml of tetrahydrofuran was added a solution of 0.42 g of N-acetyl ethanolamine and 2 ml of triethylamine in 15 ml of tetrahydrofuran. This mixture was stirred for 12 hours, then poured into water and extracted with ether. The ether extract was washed with 2N hydrochloric acid and brine, then dried and evaporated. The residual yellow oil was purified by flash chromatography, eluding with hexane:ethyl acetate (2:1), giving 0.32 g of the desired product as a pale yellow oil.

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, N-Acetylethanolamine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; American Cyanamid Company; US5053426; (1991); A;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Related Products of 5466-88-6,Some common heterocyclic compound, 5466-88-6, name is 2H-1,4-Benzoxazin-3(4H)-one, molecular formula is C8H7NO2, 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 a stirred solution of 4H-Benzo[1,4]oxazin-3-one (2.5 g, 16.77 mmol) in DMF (10 mL) was added potassium tert-butoxide (2.81 g, 25.16 mmol) at 0 C. After stirring for 5 min, methyl iodide (3.54 g, 25.16 mmol) was added and the reaction mixture was stirred for another 3h. The reaction was quenched by addition of water and extracted with ethyl acetate (30 x 2 mL). The organic layer was washed with water (20 mL), and evaporated to get a crude product 2.2 g.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2H-1,4-Benzoxazin-3(4H)-one, its application will become more common.

Reference:
Patent; NOVARTIS AG; BEBERNITZ, Gregory, Raymond; BOCK, Mark, G.; REDDY, Dumbala Srinivas; HAJARE, Atul Kashinath; VYAVAHARE, Vinod; BHOSALE, Sandeep Bhausaheb; KURHADE, Suresh Eknath; SALUNKHE, Videsh; SHAIKH, Nadim, S.; BHUNIYA, Debnath; PALLE, P., Venkata; FENG, Lili; LIANG, Jessica; WO2011/48112; (2011); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 37045-73-1, name is 3-(Methylsulfonamido)aniline, 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 37045-73-1, category: amides-buliding-blocks

Under nitrogen or argon, 0.4 mmol, 0.2mmol, Ir(ppy) 3(2mg) and DMF1 ml was added to the reaction flask, followed by blue LED lights(7W) at room temperature irradiation straight trivalent iodine reagent completeconversion of the reaction. Add 10 ml of saturated Na 2CO 3Aqueous solution, andextracted three times with ethyl acetate, the organic layer was washed with water andonce with saturated brine, dried over anhydrous Na 2SO 4The organic layer was dried.Column chromatography (eluent: petroleum ether 60-90: ethyl acetate = 10: 1-5: 1) to Ethyl acetate = 10: 1-5: 1) to give the product , S; Yield 43%.Rate of 19%.

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; Nanjing University; Zhu, ChengJian; Xie, jin; Xu, Pan; (13 pag.)CN103553857; (2016); B;,
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. 194920-62-2, name is tert-Butyl (3-(2-(2-(3-aminopropoxy)ethoxy)ethoxy)propyl)carbamate, A new synthetic method of this compound is introduced below., Quality Control of tert-Butyl (3-(2-(2-(3-aminopropoxy)ethoxy)ethoxy)propyl)carbamate

In four flasks (20mL), compound IX (0.45mmol in each) was dissolved in DMF (5mL in each) and afterwards, compounds I, II, V, or VI (2mmol), HOAt (3mmol), PyAOP (2mmol) and DIPEA (8mmol), were added to each flask. The reaction mixture of each flask was heated at 100C for 12h, diluted with water and extracted three times with DCM. Each organic layer was dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. Finally, each residue was purified by column chromatography using hexane/ethyl acetate as the solvent and thus compounds 5 (94%), 6 (91%), 7 (86%), or 8 (90%) were yielded, respectively.

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:
Article; Medina-O’Donnell, Marta; Rivas, Francisco; Reyes-Zurita, Fernando J.; Martinez, Antonio; Martin-Fonseca, Samuel; Garcia-Granados, Andres; Ferrer-Martin, Rosa M.; Lupianez, Jose A.; Parra, Andres; European Journal of Medicinal Chemistry; vol. 118; (2016); p. 64 – 78;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Electric Literature of 6919-61-5, A common heterocyclic compound, 6919-61-5, name is N-Methoxy-N-methylbenzamide, molecular formula is C9H11NO2, 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.

To a solution of 5.0g (25.4 mmol) of tetaut-butyldimethyl-pent-4-ynylochiy-silane (prepared by the method of Koseki, Y.; Sato, H.; Watanabe, Y.; Nagasaka, T. Org. Lett. 2002, 4, 885-888) in 10OmL of THF at -78C under an atmosphere of N2 was added dropwise 10.2 mL (25.4 mmol) of 2.5 M nBuLi in hexane. After stirring for Ih at that temperature, 4.0 g (24.2 mmol) of N-methoxy-N-methyl benzamide (2-1) in 20 mL of THF was added, the cooling bath was removed, and stirring was continued for 3h at room temperature. The reaction was quenched with saturated aqueous NH4Cl, extracted with 2 x EtOAc, washed with brine, dried over Na2SO4, and concentrated. The crude material was loaded onto a 4Og silica gel cartridge and eluted with a gradient of 0 to 55% EtOAc in hexanes over 25 minutes to provide 6.3g (20.9 mmol, 87%) of the propargylic ketone (2-2) as a pale yellow oil. To a suspension of 2.2g (10.7 mmol) of CuBrOMS in 30 mL of THF at -78C was added 10.7 mL (21.4 mmol) of a 2.0 M solution of PhLi in dibutylether. After stirring for 1.5h, 2.7g (8.9 mmol) of the above prepared ketone 2-2 in 5mL of THF was added, and the mixture was allowed to stir for an additional 3h at -78C, and warmed to 00C for 15 minutes before being quenched with saturated aqueous NH4Cl. The mixture was partitioned with EtOAc, the layers were separated, the aqueous was extracted with 2 x EtOAc, the organics were combined, washed with brine, dried over Na2SO4, and concentrated. The crude material was loaded onto a 4Og silica gel cartridge and eluted with a gradient of 0 to 25% EtOAc in hexanes to provide 2.89g (7.6 mmol, 85%) of 2-3 as a yellow oil; NMR analysis indicated that there was a 1.1:1 mixture of E:Z isomers. Careful separation of a fraction of this material provided the pure isomers, whose identities were determined by ID NOE analysis. Data for 2-3-(E) (first to elute): 1HNMR (500 MHz, CDCl3) delta 8.0 (m, 2H), 7.6 – 7.4 (m, 8H), 7.1 (s, IH), 3.7 (t, J = 6.3 Hz, 2H), 3.1 (m, 2H), 1.75 (m, 2H), 0.9 (s, 9H), 0.01 (s, 6H) ppm. Data for 2-3-(Z) (second to elute): 1HNMR (500 MHz, CDCl3) delta 7.8 (m, 2H) 7.45 (m, IH), 7.35 (m, 2H), 7.25 – 7.1 (m, 5H), 6.7 (s, IH), 3.65 (t, J = 6.3 Hz, 2H), 2.65 (t, J = 7.6 Hz, 2H), 1.7 (m, 2H), 0.9 (s, 9H), 0.05 (s, 6H) ppm. Data for mixture 2-3: HRMS (ES) calc’d M + H for C24H32O2Si: 381.2245. Found: 381.2251

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; MERCK & CO., INC.; WO2006/7501; (2006); A2;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics