Month: March 2021

22117-85-7, name is 2-Methoxy-5-sulfamoylbenzoic acid, 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. category: amides-buliding-blocks

EXAMPLE 53 N-(1-Cyclohexyl-3-pyrrolidinyl)-2-methoxy-5-sulfamoylbenzamide To 3.7 g. (0.022 mole) of 3-amino-1-cyclohexylpyrrolidine in 100 ml. of pyridine was added dropwise with cooling 1.1 g. (0.008 mole) of phosphorous trichloride at 20C. After stirring one hour, 3 g. (0.013 mole) of 2-methoxy-5-sulfamoylbenzoic acid was added and refluxed 6 hrs. The solution was concentrated and the residue partitioned between dilute hydrochloride acid and isopropyl ether. The acid was made basic with ammonium hydroxide and extracted with chloroform which was dried (sodium sulfate) and concentrated. The residue was crystallized from ethyl acetate and recrystallized from isopropyl alcohol. Yield 1 g. (33%); m.p. 184-187C. Anaylsis: Calculated for C18 H27 N3 O4 S: C,56.67; H,7.13; N,11.02. Found: C,56.39; H,7.09; N,11.00.

The synthetic route of 22117-85-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; A. H. Robins Company, Incorporated; US3966957; (1976); A;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Reference of 112101-81-2,Some common heterocyclic compound, 112101-81-2, name is R-5-(2-Aminopropyl)-2-methoxybenzenesulfonamide, molecular formula is C10H16N2O3S, 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 1: Preparation of 5-[(2R)-2-[[2-(2-ethoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzene-sulfonamide (Tamsulosin base)(R)-5-(2-arriinopropyl)-2-methoxybenzenesurfonarnide (60 g; 245.59 mmol) and l-(2- bromoethoxy)-2-ethoxybenzene (57.25 g; 233 mmol) were dissolved in 240 mL of N5N- dimethylformamide and 50.5 mL of diisopropylethylamine. The reaction mixture was heated to 100 C and stirred for 90 minutes. The mixture was then cooled to 20 C and 720 mL of ethyl acetate and 300 mL of water added to the vessel. The mixture was then stirred for 20 minutes at atmospheric condition, and then was allowed to settle. The aqueous layer was separated and re-extracted twice with 300 mL of ethyl acetate. The organic layers were combined and washed with 600 mL of water.The organic phase (1120 mL of ethyl acetate) was then concentrated by distillation at atmospheric pressure during which a white solid was precipitated. The mixture was then cooled to 2 C and stirred for 1 hour. The resulting crystals were isolated by filtration and washed with ethyl acetate to yield 133.59 g of wet tamsulosin base (Loss on Drying: 55.08% (corresponding to 60.01 g of dry material); HPLC Purity: 95.025%).EXAMPLE 3: Preparation of 5-[(2R)-2-[[2-(2-ethoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzene-sulfonamide (Tamsulosin base)(R)-5-(2-aminopropyl)-2-methoxybenzenesulfonamide (100 g; 409.31 mmol) and 1- (2-bromoethoxy)-2-ethoxybenzene (95.4 g; 388 mmol) were dissolved in 400 mL of N,N- dimethylformamide and 84 mL of diisopropylethylamine. The reaction mixture was heated to 100 C and stirred for 90 minutes. The mixture was then cooled to 20 C, and 1200 mL of ethyl acetate and 500 mL of water were added. The mixture was then stirred for 20 minutes at atmospheric conditions and was allowed to settle. The aqueous layer was then separated and re-extracted twice with 500 mL of ethyl acetate. Next, the organic layers were combined and washed with 1000 mL of water.The organic phase (~1570 mL of ethyl acetate) was then concentrated by distillation at atmospheric pressure during which a white solid was precipitated. The mixture was then cooled to 2 C, and stirred for 1 hour. The resulting crystals were isolated by filtration and washed with ethyl acetate to yield 125.93 g of wet tamsulosin base (Loss on Drying: 24.09% (corresponding to 95.59 g of dry material); HPLC Purity: 97.62%). EXAMPLE 4: Preparation of 5-[(2R)~2-[[2-(2-ethoxyphenoxy)ethyl]amino]propyI]-2- methoxybenzene-sulfonamide (Tamsulosin base)(R)-5-(2-arninopropyl)-2-methoxybenzenesulfonamide (3 g; 12.27 mmol) and l-(2- bromoethoxy)-2-ethoxybenzene (2.86 g ; 11.63 mmol) were dissolved in 12 mL of N5N- dimethylformamide and 2.55 mL of diisopropylemylamine. The reaction mixture was heated to 100 C and stirred for 90 minutes. The mixture was then cooled to 20 C, and 36 mL of ethyl acetate and 15 mL of water were added. The mixture was then stirred for 20 minutes at atmospheric conditions and was allowed to settle. The aqueous layer was then separated and re-extracted twice with 15 mL of ethyl acetate. Next, the organic layers were combined and washed with 75 mL of water.The organic phase (~80 mL of ethyl acetate) was concentrated by distillation at atmospheric pressure during which a white solid was precipitated. The mixture was then cooled to 2 C and stirred for 1 hour. The resulting crystals were isolated by filtration and washed with ethyl acetate to yield 5.14 g of wet tamsulosin base (Loss on Drying: 39.68% (corresponding to 3.1 g of dry material); HPLC Purity: 96.65%).The solid obtained in the previous step was then combined with 31 mL of ethanol. The reaction mixture was then heated to 78 C and stirred for 40 minutes, cooled to 0 C and stirred for 150 minutes. The resulting crystals were isolated by filtration to yield 4.92 g of wet tamsulosin base (Loss on Drying: 40.59% (corresponding to 2.81 g of dry material); HPLC Purity: 98.70%).

The synthetic route of 112101-81-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MEDICHEM, S.A.; WO2007/119110; (2007); A2;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Some common heterocyclic compound, 17641-08-6, name is 2-Chloro-N-(3-methoxyphenyl)acetamide, molecular formula is C9H10ClNO2, 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 2-Chloro-N-(3-methoxyphenyl)acetamide

General procedure: A mixture of the potassium salt 22 (1.5g, 0.01mol) and the appropriate chloroacetanilides (0.01mol) namely, 2-chloro-N-(3-methoxyphenyl)acetamide and 2-chloro-N- (4-fluorophenyl)acetamide in dry DMF (20ml) was heated over a water bath for 3h. The reaction mixture was then cooled, poured into ice-cooled water (150ml) and stirred well for 30min. The solid such separated was filtered, washed with water, dried and crystallized from methanol/toluene mixture (1:1) to afford the corresponding compounds 25a – b, respectively. 2-(Bis[1,2,4]triazolo[4,3-a:3?,4?-c]quinoxalin-3-ylsulfanyl)-N-(3-methoxyphenyl) acetamide (25a). White crystal (yield 71 %); m. p. 256 – 259 C; IR (KBr, cm1); 3264 (NH), 3077 (CH aromatic), 2950 (CH aliphatic), 1689 (C=O amide); 1H NMR (DMSO-d6) delta ppm: 3.70 (s, 3H, -OCH3), 4.52 (s, 2H, CH2), 6.62 (d, 1H, J=8.1Hz, Ar-H, H-4 of phenyl), 6.69 (d, 1H, J=8.4Hz, Ar-H, H-6 of phenyl), 7.20 (dd, 1H, J=8.1, 8.4Hz, Ar-H, H-5 of phenyl), 7.23 (s, 1H, Ar-H, H-2 of phenyl), 7.72 (dd, 1H, J=7.8, 8.4Hz, Ar-H, H-7 of quinoxaline), 7.74 (dd, 1H, J=7.8, 8.1Hz, Ar-H, H-6 of quinoxaline), 8.45 (d, 1H, J=8.4Hz, Ar-H, H-8 of quinoxaline), 8.59 (d, 1H, J=8.1Hz, Ar-H, H-5 of quinoxaline), 10.02 (s, 1H, Ar-H, N-CH=N), 10.54 (s, 1H, -NH, D2O exchangeable); 13C NMR (DMSO-d6, 100 MHz) delta (ppm): 38.9, 55.4, 105.4, 109.4, 111.8, 118.0, 118.5, 123.1, 124.0, 128.3 (2), 130.0, 138.7, 139.4, 140.3, 142.3, 147.7, 159.9, 165.5; DEPT (DMSO-d6, 100 MHz) delta (ppm): 38.9 (1CH3), 55.4 (1CH2), 105.3, 109.4, 111.8, 118.0, 118.5, 128.3 (2), 130.0, 138.7 (9CH); Anal. Calcd. for C19H15N7O2S (405.43): C, 56.29; H, 3.73; N, 24.18. Found: C, 56.42; H, 3.71; N, 24.39 %.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 17641-08-6, its application will become more common.

Reference:
Article; Ibrahim; Taghour; Metwaly; Belal; Mehany; Elhendawy; Radwan; Yassin; El-Deeb; Hafez; ElSohly; Eissa; European Journal of Medicinal Chemistry; vol. 155; (2018); p. 117 – 134;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Application of 174799-52-1, A common heterocyclic compound, 174799-52-1, name is tert-Butyl (2-(benzylamino)ethyl)carbamate, molecular formula is C14H22N2O2, 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.

41 c (5.00g, 17.96 mmol) and 56 (4.497g, 17.96 mmol, 1 eq) were dissolved in EtOH (30 mL) and a few drops of water added, before splitting the mixture into 2 x 30 mL W vessels. Each mixture was heated at 100 C for 30 mins in the MW reactor (dynamic program with maximum pressure 250 psi, maximum power 300W). Concentration of the reaction mixture gave approximately 10 g of crude residue. This was purified by FCC (eluent PE/DCM 1 :1 to prime/load the column, with the gradient increasing to 100% DCM over 5CV, 1 00% DCM for a further 3 CV and then raise to DCM/MeOH 99:1 over 1 CV, then to 95:5 over 3 CV, holding at this concentration to elute the desired product). This gave 7.30 (77%) g of white crystalline solid.

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; THE UNIVERSITY OF NOTTINGHAM; MISTRY, Shailesh; DARAS, Etienne; FROMONT, Christophe; JADHAV, Gopal; FISCHER, Peter Martin; KELLAM, Barrie; HILL, Stephen John; BAKER, Jillian Glenda; WO2012/4549; (2012); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Synthetic Route of 103361-99-5,Some common heterocyclic compound, 103361-99-5, name is 7-Fluoro-2H-benzo[b][1,4]oxazin-3(4H)-one, molecular formula is C8H6FNO2, 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 2H-1 ,4-benzothiazin-3(4H)-one (intermediate 33, 3.1 g, 18.55 mmol) in dry Toluene (15 mL) in a glass tube was added Lawesson’s reagent (4.50 g, 1 1 .13 mmol, 0.6 eqv) and the mixture reacted in a microwave reactor at 100 C for 5 minutes). Cyclohexane was added, and the resulting solid was filtered. The solid was dissolved in Et^O and the solvent removed not quite to dryness. This concentrated mixture was purified using a Biotage SP1 purification system using Normal phase Silica SNAP 4×50 g (because of low solubility) column in the gradient of ethyl acetate in cyclohexane (8 % in 1 CV, 8-30 % in 10 CV, 30-66 % in 10 CV) to give the title compound (2 g); m/z (ES): 184.10 [M+H]+; 1H NMR (600 MHz, DMSO-d6) delta ppm 4.86 (s, 2 H) 6.84 – 6.88 (m, 1 H) 6.92 – 6.97 (m, 1 H) 7.07 – 7.1 1 (m, 1 H) 12.77 (s, 1 H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 7-Fluoro-2H-benzo[b][1,4]oxazin-3(4H)-one, its application will become more common.

Reference:
Patent; GLAXO GROUP LIMITED; BERTANI, Barbara; CREMONESI, Susanna; GARZYA, Vincenzo; MICHELI, Fabrizio; RUPCIC, Renata; SABBATINI, Fabio Maria; WO2011/151361; (2011); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Reference of 16066-84-5, A common heterocyclic compound, 16066-84-5, name is tert-Butyl methylcarbamate, molecular formula is C6H13NO2, 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 Preparation of Compound c71 (0551) Compound c70 (1.0g, 4.15mmol) was dissolved in dioxane (16mL), and tertiary butyl methyl carbamate (653mg, 4.98mmol), 2- dicyclohexylphosphino-2 ‘, 4′ , 6’-triisopropyl-biphenyl (297mg, 0.622mmol), potassium phosphate (2.20g, 10.73mmol) and tris (dibenzylideneacetone) palladium (190mg, 0.207mmol) were added to the mixture at 100 C for 5 hours. Tertiary butyl methyl carbamate (218mg, 1.66mmol), 2-dicyclohexylphosphino-2 ‘, 4′, 6’-triisopropyl biphenyl (99mg, 0.207mmol), potassium phosphate (0.73g, 3.57mmol) and tris (dibenzylideneacetone) palladium (0) (63.3mg, 0.069mmol) were added to the mixture and the mixture was stirred for 3 hours. Tertiary butyl methyl carbamate (435mg, 3.32mmol), 2- dicyclohexylphosphino-2 ‘, 4′, 6’-triisopropyl biphenyl (99mg, 0.207mmol) and tris (dibenzylideneacetone) palladium (0) (63.3mg, 0.069mmol) was then added to the mixture and the mixture was stirred for 5.5 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give compound c71 (0.75g, 74% yield). [M + H] = 244.95, Method Condition 3: retention time 2.08 min

The synthetic route of 16066-84-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shionogi & Co., Ltd.; KOBAYASHI, Naotake; ASAHI, Kentarou; TOMIDA, Yutaka; OHDAN, Masahide; FUMOTO, Masataka; SASAKI, Yoshikazu; KURAHASHI, Kana; INOUE, Takatsugu; URABE, Tomomi; NISHIURA, Yuji; IWATSU, Masafumi; MIYAZAKI, Keisuke; OHYABU, Naoki; WADA, Toshihiro; KATOU, Manabu; (276 pag.)EP3059225; (2016); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Electric Literature of 19047-31-5,Some common heterocyclic compound, 19047-31-5, name is 2-Chloro-N-cyclopropylacetamide, molecular formula is C5H8ClNO, 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 2-chloro-N-cyclopropylacetamide (1.33 g, 10 mmol), 3- bromobenzenethiol (1.6 g, 8.5 mmol) and K2CO3 (4.8 g, 35 mmol) in 30 mL of acetone was heated at 70 C overnight. The mixture was filtered and concentrated to give a residue, which was purified by column chromatography (PE/EA, 1/1) to give the title compound (2.4 g, 96%) as a white solid. 1H NMR delta (300 MHz, CDC13) 7.39 (1H, m), 7.31 (1H, m), 7.14 (2H, m), 6.71 (1H, s), 3.58 (2H, s), 2.64-2.77 (1H, m), 0.73-0.84 (2H, m), 0.41 (2H, m); m/e 286 (M+H)+.

The synthetic route of 19047-31-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KADMON CORPORATION, LLC; BOXER, Michael; RYAN, John; TONRA, James; WO2014/55999; (2014); A2;,
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. 67341-01-9, name is tert-Butyl (2-hydroxy-1-phenylethyl)carbamate, A new synthetic method of this compound is introduced below., Formula: C13H19NO3

General procedure: To a solution of compound 4 (1 mmol) in CH2Cl2 (3 mL) wereadded trimethylamine (1.3 mmol) and methansulfonylchloride(1.1 mmol). After stirring at room temperature for 30 min, themixture was diluted with dichloromethane and washed withsaturated sodium bicarbonate solution. The organic layer was driedover sodium sulfate and filtered. After concentration, the filtratewas dried in vacuo to give compound 4a. The mixture of compound9 or 10 (1 mmol), the mesylate 4a (2.5mmol) and K2CO3 (5mmol) inDMF (10 mL) was stirred at 70 C overnight. The reaction mixturewas cooled to ambient temperature, diluted with ethyl acetate, andwashed with saturated ammonium chloride solution. The organiclayer was concentrated, then the residue was purified using silicagel and amine silica gel chromatography (hexane/EtOAc, 2:1). Thealkylated compound (1 mmol) in CH2Cl2 (40 mL) was treated withTFA (2 mL), stirring at room temperature for 3 h. The reactionmixture was neutralized with saturated NaHCO3 and extractedwith CH2Cl2 twice. The organic layer was concentrated, then purifiedusing silica gel chromatography (CH2Cl2/MeOH, 15:1-20:1).

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; Kim, Seon-Mi; Lee, Minhee; Lee, So Young; Lee, Soo-Min; Kim, Eun Jeong; Kim, Jae Sun; Ann, Jihyae; Lee, Jiyoun; Lee, Jeewoo; European Journal of Medicinal Chemistry; vol. 145; (2018); p. 413 – 424;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Synthetic Route of 263349-73-1,Some common heterocyclic compound, 263349-73-1, name is 4-Bromo-3-fluorobenzenesulphonamide, molecular formula is C6H5BrFNO2S, 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 vessel was charged with 4-bromo-3-fluorobenzenesulfonamide (2, 255 mg, 1.00 mmol), Bis(pinacolato)diboron (280 mg, 1.10 mmol), Potassium acetate (295 mg, 3.01 mmol) and degassed dry 1,4-dioxane (5.02 mL). The vessel was evacuated and backfilled with argon (3x), XPhos Pd G4 (4.32 mg, 0.00502 mmol) was added and the mixture stirred at 85 C for overnight. After cooling to RT, the mixture was diluted with EtOAc and Acetic Acid (0.172 mL, 3.01 mmol), stirred for 30 minutes and filtered over Celite. The solvent was removed under reduced pressure. The residue was dissolved in a minimum amount of EtOAc, precipitated with n-heptane and the solids collected by suction filtration to yield 3-fluoro-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide (220 mg, 0,7310 mmol, 73% yield) which was used without further purification. (0844) Analytical data: (0845) 1H NMR (200 MHz, DMSO) delta 7.91- 7.09 (m, 5H), 1.42- 0.95 (m, 12H); (0846) 13C NMR (50 MHz, DMSO) delta 148.6 (d, J = 8.2 Hz), 137.5 (d, J = 8.3 Hz), 121.05 (d, J = 2.1 Hz), 112.48 (d, J = 27.6 Hz), 83.9, 73.6, 25.0, 24.7.

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

Reference:
Patent; HEPAREGENIX GMBH; PRAEFKE, Bent; KLOeVEKORN, Philip; SELIG, Roland; ALBRECHT, Wolfgang; LAUFER, Stefan; (157 pag.)WO2019/149738; (2019); 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. 456-64-4, name is 1,1,1-Trifluoro-N-phenylmethanesulfonamide, A new synthetic method of this compound is introduced below., Safety of 1,1,1-Trifluoro-N-phenylmethanesulfonamide

To a solution of N-carbethoxy-4-tropinone (2-1) (15.0 g, 76.1 mmol) in 150 mL anhydrous tetrahydrofuran at-78 C was slowly added KN (TMS) 2 (182 mL, 0.5 ML in toluene). The solution was stirred at-78 C for 30 minutes, and then a solution of N-phenyltrifluoromethane sulfonamide (32.6 g, 91. 3 mmol) in 150 mL anhydrous tetrahydrofuran was added. The mixture was stirred at-78 C for 2 h and quenched with a saturated aqueous ammonium chloride (150 mL). After the removal of tetrahydrofuran under vacuum, the aqueous layer was then extracted with EtOAc (3 x 150 mL). The combined EtOAc layers were washed with IN KOH (150 ml), brine, dried over anhydrous magnesium sulfate, filtered, and concentrated. Purification of the crude residue by flash chromatography over silica gel (gradient elution; 0%-30% ethyl acetate/hexanes as eluent) afforded (2-2) as a colorless oil.

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.; WO2004/87159; (2004); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics