Month: February 2021

Adding a certain compound to certain chemical reactions, such as: 1065114-27-3, name is tert-Butyl 2,4-dichloro-8,9-dihydro-5H-pyrimido[4,5-d]azepine-7(6H)-carboxylate, 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 1065114-27-3, SDS of cas: 1065114-27-3

2,4-Dichloro-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine hydrochloride (4.79 g, 18.4 mmol) was suspended in dichloromethane (50 mL), and the suspension was mixed with di-tert-butyl dicarbonate (6.0 g) and triethylamine (7.7 mL), followed by stirring at room temperature for thirty minutes. The reaction mixture was mixed with a saturated aqueous sodium bicarbonate solution, was stirred for a while and was separated. The organic layer was washed with brine and was dried over anhydrous sodium sulfate. After distilling off the solvent, the whole quantity of the residue was dissolved in tetrahydrofuran (50 mL), and the solution was mixed with 2 , 4-dichlorobenzylamine (4.2 mL) and triethylamine (11.5 mL), followed by stirring at 40C for 21 . 5 hours. The reaction mixture was diluted with water and was extracted with ethyl acetate. The organic layer was washed with brine, was dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was mixed with ethyl acetate for crystallization. The precipitated crystals were collected by filtration, were dried and thereby yielded tert-butyl 2-chloro-4-(2,4-dichlorobenzylamino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-7-carboxylate (4.27 g). After concentrating the filtrate, the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=3:1) and thereby yielded the target compound (0.76 g, 5.03 g in total with the above-mentioned crystals, in a yield of 60%).

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, tert-Butyl 2,4-dichloro-8,9-dihydro-5H-pyrimido[4,5-d]azepine-7(6H)-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; KYOWA HAKKO KOGYO CO., LTD.; EP1552842; (2005); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Reference of 96-30-0, A common heterocyclic compound, 96-30-0, name is 2-Chloro-N-methylacetamide, molecular formula is C3H6ClNO, 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 suspension of Intermediate 7 (500 mg, 1.48 mmol), K2C03 (204 mg, 1.48 mmol) and potassium thioacetate (590 mg, 5.16 mmol) in DMF (5.5 mL) was heated at 140C under microwave irradiation for 3 h. After cooling, the mixture was dissolved in water (20 mL), neutralized to pH 6 with 1M HCl and extracted with EtOAc (3 x 50 mL). The organic layer was washed with saturated brine (3 x 30 mL), dried (MgS04) and concentrated in vacuo. Purification by column chromatography on silica, eluting with 5% EtOAc in DCM, gave a yellow solid (127 mg, 26%). LCMS (ES+) 337 (M+H)+. A suspension of this solid (114 mg, 0.339 mmol), K2C03 (46.8 mg, 0.339 mmol) and 2- chloro-N-methylacetamide (87 mg, 0.809 mmol) in DMF (3 mL) was heated at 120C under microwave irradiation for 1 h. After cooling, the mixture was dissolved in a 1 : 1 mixture of EtOAc and Et20 (150 mL) and washed with saturated brine (3 x 30 mL). The organic layer was dried (MgS04) and concentrated in vacuo. Purification by column chromatography on silica, eluting with 40% EtOAc in DCM, gave a white solid (119 mg, 86%). LCMS (ES+) 408 (M+H)+. This solid (119 mg, 0.292 mmol) was dissolved in DCM (7.6 mL) and TFA (1.33 mL) was added. The reaction mixture was stirred at r.t. for 1.5 h and concentrated in vacuo. The residue obtained was basified with 0.8M aqueous NaOH (8 mL) and extracted with EtOAc (3 x 30 mL). The combined organic layers were dried (MgS04) and concentrated in vacuo to give a colourless glass (117 mg, 100%). LCMS (ES+) 308 (M+H)+. A solution of this material (117 mg, 0.292 mmol), 2,4-dichloro-5-cyanopyrimidine (76.2 mg, 0.438 mmol) and DIPEA (0.20 mL, 1.168 mmol) in THF (2 mL) was stirred at r.t. for 4 h. The mixture was dissolved in EtOAc (150 mL) and washed with saturated brine (3 x 30 mL). The organic layer was dried (MgS04) and concentrated in vacuo. Purification by column chromatography on silica, eluting with DCM/MeOH NH3 solution in MeOH (98: 1 :1), gave a pale brown foam (105 mg, 81%). LCMS (ES+) 445, 447 (M+H)+ (mixture of regioisomers). A solution of this material (105 mg, 0.236 mmol) in a mixture of 7M NH3 solution in MeOH (2 mL) and NH4OH (1 mL) was heated at 120C under microwave irradiation for 1 h. After cooling, the mixture was dissolved in saturated brine (40 mL) and extracted with EtOAc (3 x 100 mL). The organic layer was dried (MgS04) and concentrated in vacuo. Purification by preparative HPLC afforded the title compound (13.2 mg, 13%) as an off-white solid, delta? (DMSO-d6) 8.31 (1H, s), 8.25 (1H, s), 8.15 (1H, d, J5.33 Hz), 7.87-7.81 (2H, m), 7.40 (1H, t, J9.13 Hz), 7.15 (1H, br s), 6.97 (1H, br s), 5.55-5.46 (1H, m), 4.10 (1H, d, J 15.2 Hz), 4.04 (1H, d, J 15.2 Hz), 2.65 (3H, d, J4.59 Hz), 2.58 (3H, s), 1.61 (3H, d, J 6.82 Hz). LCMS (ES+) 426 (M+H)+, T 3.37 minutes {Method 1).

The synthetic route of 96-30-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UCB PHARMA S.A.; RAPHY, Gilles; BUeRLI, Roland; HAUGHAN, Alan, Findlay; WO2011/58113; (2011); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Reference of 1171331-39-7, The chemical industry reduces the impact on the environment during synthesis 1171331-39-7, name is 2-Amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride, I believe this compound will play a more active role in future production and life.

Example 108 Preparation of (Z)-2-Bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC95) To a stirred solution of (Z)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid (200 mg, 0.41 mmol) in anhydrous THF (5.0 mL) was added carbonyldiimidazole (82 mg, 0.51 mmol). The mixture was heated in a 50 C. oil bath for 1.5 h, treated with 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride (109 mg, 0.057 mmol) and the resulting mixture heated to reflux for 8 h. After cooling to ambient temperature, the mixture was taken up in Et2O and washed twice with aqueous 5% sodium bisulfate (NaHSO4) (2*) and once with saturated NaCl (1*). After dying over MgSO4, concentration in vacuo and purification by medium pressure chromatography on silica with EtOAc/Hexanes as the eluents, the title compound was obtained as a white foam (160 mg, 41%) mp 48-61 C.: 1H NMR (400 MHz, CDCl3) delta 7.58 (d, J=7.9 Hz, 1H), 7.44-7.29 (m, 3H), 7.14 (dd, J=7.9, 1.6 Hz, 1H), 6.86 (d, J=11.4 Hz, 1H), 6.76 (t, J=5.9 Hz, 1H), 6.59 (br s, 1H), 6.21-6.04 (m, 1H), 4.23 (d, J=5.5 Hz, 1H), 3.98 (qd, J=9.0, 6.5 Hz, 2H); 19F NMR (376 MHz, CDCl3) delta -69.31, -72.3; EIMS m/z 626.9 ([M+1]+).

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, 2-Amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Dow AgroSciences LLC; Lo, William C.; Hunter, James E.; Watson, Gerald B.; Patny, Akshay; Iyer, Pravin S.; Boruwa, Joshodeep; US2014/171314; (2014); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

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. 2832-19-1, name is 2-Chloro-N-(hydroxymethyl)acetamide belongs to amides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Application In Synthesis of 2-Chloro-N-(hydroxymethyl)acetamide

The starting material was prepared as follows: 2-Chloro-N-(hydroxymethyl)-acetamide (0.342 g; 2.7 mmol), triphenylphosphine (1.1 g; 4.19 mmol) and DEAD (0.6 ml; 4.19 mmol) were added to a solution of N-acetyl-colchicinol (0.3 g; 0.84 mmol) in dichloromethane (20 ml) under argon atmosphere. The mixture was stirred at ambient temperature for 2 hours, evaporated and purified by flash chromatography eluding with ethyl acetate/dichloromethane (50/50) and dichloromethane/methanol (98/2) to give (1). Yield: 76 % MS-ESI: 485.1 [MH]+

The synthetic route of 2832-19-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Angiogene Pharmaceuticals Ltd; EP1140745; (2003); B1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

25625-57-4, name is 2-Bromo-N-(3-(trifluoromethyl)phenyl)acetamide, 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. Application In Synthesis of 2-Bromo-N-(3-(trifluoromethyl)phenyl)acetamide

Sodium hydride in mineral oil (21.40 mg, 0.535 mmol) was added to a, stirring, ice-bath cooled solution of 3-[4-(4,5-dimethyl-1 H-imidazol-1 -yl)phenyl]-1 , 4-diazaspiro[4.4]non-3- en-2-one (D28) (150 mg, 0.486 mmol) in DMF (5 ml) under argon. After stirring for 30 min. a solution of 2-bromo-N-[3-(trifluoromethyl)phenyl]acetamide (D8) (137 mg) in DMF (3 ml) was added over 1 h using a syringe pump maintaining an ice-bath temperature. The resulting reaction mixture was allowed to come to room temperature then stirred for a further 4 h. The reation mixture was diluted with methanol (20 ml) and applied to an SCX column (1Og). After washing with MeOH (50 ml) the product was eluted with 2M NH3-MeOH. Evaporation of the solvent afforded a brown gum. On dissolving in 1 :1MeOH:DMSO for MDAP purification a small amount of white solid precipitated. This was collected, washed with diethyl ether and dried The material was reapplied to an SCX column (1g) in MeOH (10 ml), washing (30 ml MeOH) and eluting as described above to remove residual DMSO. Drying afforded the free-base of the title compound as a white solid (20 mg).1H NMR (CDCI3) delta: 1.80 – 2.15 (8H, bm), 2.17 (3H, s, overlapping with adjacent bm), 2.25 (3H, s), 4.30 (2H, s), 7.40 (4H, m), 7.58 (1 H, s), 7.68 (1 H, d), 7.84 (1 H, s), 8.57 (2H, d),9.32 (1 H, s).Mass Spectrum (Electrospray LC/MS): Found 510 (MH+). C27H26F3N5O3 requires 509. Ret. time 1.81 min.A solution of the free-base (20 mg) in DCM (2 ml) was treated with an excess of 1 M HCI in diethyl ether (0.12 ml, 0.120 mmol). The volatiles were removed in vacuo and the residue dried under high vacuum at 550C to afford the title hydrochloride as a pale yellow solid (20 mg).Mass Spectrum (Electrospray LC/MS): Found 510 (MH+). C27H26F3N5O3 requires 509. Ret. time 1.77 min.

The synthetic route of 25625-57-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXO GROUP LIMITED; WO2009/34061; (2009); A1;,
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. 122334-37-6, name is 4-Chloro-N-methoxy-N-methylbenzamide, A new synthetic method of this compound is introduced below., Application In Synthesis of 4-Chloro-N-methoxy-N-methylbenzamide

Ethylmagnesium bromide (3.0 M in diethyl ether, 21.5 mL, 64.4 mmol) was added via syringe over a period of several minutes in an ice bath under nitrogen atmosphere to a solution of 5-bromo-1-methyl-1H-imidazole G, 64.4 mmol). A white precipitate was formed upon addition. The mixture was removed from the ice bath, stirred for 20 min and then cooled again in an ice bath before addition of 4-chloro-N-methoxy-N-methylbenzamide (10.7 g, 53.6 mmol, intermediate 1: step a) . The resulting white suspension was stirred at room temperature overnight. The reaction was quenched by the addition of a saturated aqueous NH4Cl solution and diluted with water. The mixture was partially concentrated, the THF was removed and diluted with DCM. The mixture was acidified to pH 1 with 1 N HCl aqueous solution and then neutralized with saturated aqueous NaHCO3 solution. The phases were separated and the aqueous phase further extracted with DCM. The organic extracts were washed with water, then dried (Na2SO4), filtered and concentrated to give a white solid. The crude product was triturated with a mixture of EtOAc: heptane (1: 1, 150 mL). The precipitated solid was collected by vacuum filtration and washed with heptane to give the title compound.

The synthetic route of 122334-37-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Janssen Pharmaceutica, N.V; Leonardo, Christie.A; Barubay, Kent; Edward, James P.; Kirsten, Kevin D.; Kumar, David A.; Maharupe, Uma; Nishimura, Rachel; Urbanski, Modu; Venkatesan, Hariharan; Wang, Ai Hua; OhLynn, Ronald L.; Woods, Craig R.; Fourier, Anne; Shu, Jia Hu; Cummings, Maxwell D.; (50 pag.)KR2016/70823; (2016); A;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

6292-59-7, name is 4-(tert-Butyl)benzenesulfonamide, 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. Product Details of 6292-59-7

A solution of compound 13 (2.0 g, 4.36 mmol) and commercially available4-tert-butylbenzenesulfoamide (1.0 g, 4.79 mmol) in toluene (30 mL) was treated withK2CO3 (723 mg, 5.23 mmol) and tetra-n-butylammonium bromide (142 mg,0.44 mmol). The reaction mixture was warmed at 100 C for 18 h and cooled downto ambient temperature. The resulting mixture was filtered through a pad of Celite,and the filtrate was diluted with EtOAc (100 mL); washed with aqueous 1N HCl,water, and brine; dried over anhydrous MgSO4; and concentrated under reducedpressure to provide the crude product. Flash chromatography (SiO2, 3percent MeOH?CH2Cl2) to provide 14 as a green foam (1.75 g, 63percent)

The synthetic route of 6292-59-7 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Lee, Chung Ryul; Lee, Sang Yeul; Nam, Tae-Gyu; Synthetic Communications; vol. 44; 17; (2014); p. 2488 – 2493;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Synthetic Route of 1939-27-1, 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. 1939-27-1 name is N-(3-(Trifluoromethyl)phenyl)isobutyramide, 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.

Step 3, put a 100ml three-necked bottle with mechanical stirring and thermometer into the ice machine, add 23ml of concentrated sulfuric acid, stir,Addition of 10.75g of iso – butyramide benzotrifluoride until the solid dissolves, keeping the temperature at -5 C, adding 2.3ml of 95% fuming HN03, stirring 3h; Step 4, the above reaction was poured into a certain amount of ice water mixture, was sticky solid, add 80g toluene, stirring,Separation, the upper organic phase was washed three times with 3% sodium bicarbonate solution, followed by three washes, and the solvent was removed by rotary evaporation to give a yellow solid; Step 5, the above yellow solid was added to the flask, 20 ml of ethanol was added, and the mixture was heated to reflux, solid 1% of activated carbon was added, stirred for 5 minutes, and hot filtered.The filtrate was cooled to room temperature, and petroleum ether was slowly added thereto until the solution became turbid. The solution was refrigerated at 0C for 3 hours, filtered, and dried at 60C to obtain flunitamide as a pale yellow solid.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, N-(3-(Trifluoromethyl)phenyl)isobutyramide, and friends who are interested can also refer to it.

Reference:
Patent; Xuzhou Nuokefei Pharmaceutical Technology Co., Ltd.; Zhao Qingling; Li Weixin; (7 pag.)CN108003051; (2018); A;,
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 4815-28-5 as follows. Product Details of 4815-28-5

General procedure: 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide(4a;1.5 mmol) was suspended in 10 ml butanol and benzaldehydes(5a-5m;1.0 mmol). Conc HCl (0.1 ml) was added to this reaction mixture and heated at 80 C for 12 h or until TLC confirms the completion of reaction. The solid obtained was filtered, washedwith water and dried.

According to the analysis of related databases, 4815-28-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Amawi, Haneen; Karthikeyan, Chandrabose; Pathak, Rekha; Hussein, Noor; Christman, Ryann; Robey, Robert; Ashby, Charles R.; Trivedi, Piyush; Malhotra, Ashim; Tiwari, Amit K.; European Journal of Medicinal Chemistry; vol. 138; (2017); p. 1053 – 1065;,
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 885-70-1 as follows. Recommanded Product: 5,11-Dihydropyrido[2,3-b][1,4]benzodiazepin-6-one

(a) 5,11-Dihydro-11-(prop-2-ynyl)-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one To a suspension of 7.4 g (0.035 mol) of 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one in 150 ml of anhydrous tetrahydrofuran, 44.8 ml (approx. 0.07 mol) of a 15% solution of n-butyl-lithium in n-hexane was added dropwise with stirring at a reaction temperature of from 0 to +10 C. After it had all been added, the mixture was stirred for 30 minutes at ambient temperature before a solution of 4.16 g (0.035 mol) of 3-bromo-prop-1-yne in 25 ml of anhydrous tetrahydrofuran was added dropwise. The resulting mixture was stirred for a further 2 hours at ambient temperature, added to 1 liter of saturated aqueous saline solution and the resulting mixture was extracted exhaustively with ethylacetate. The combined ethylacetate extracts were washed twice more with 100 ml of saturated saline solution, dried over sodium sulphate with the addition of 1 g of activated charcoal and evaporated down in vacuo. The residue was purified on silica gel by chromatography using dichloromethane/ethyl acetate 95/5 (v/v) as eluant. 8.5 g (97% of theory) of colourless crystals were obtained, m.p. 199 C. (decomposition).

According to the analysis of related databases, 885-70-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Karl Thomae GmbH; US5006522; (1991); A;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics