Author: tianli

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. 7803-58-9, name is Sulfuric diamide, A new synthetic method of this compound is introduced below., 7803-58-9

The preparation of sulfamide 16.1 is starting with commercially available, literature or readily available diamine. The treatment of diamine 16.1 with sulfamine a under refluxing pyridine affords sulfamine 16.3, which is followed by alkylation of [A-HALO] alkyl ester to give compound 16.4. Basic hydrolysis (LiOH, [H20/THF/MEOH)] of ester gives acid 16.1 as the intermediateds for example 61.

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; SUNESIS PHARMACEUTICALS, INC.; WO2003/106405; (2003); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

57561-39-4, 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. 57561-39-4 name is tert-Butyl (2-hydroxyethyl)(methyl)carbamate, 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.

To a solution of tert-butyl (2-hydroxyethyl)(methyl)carbamate (1.0 g, 5.71 mmol) and triethylamine (1.15 g, 11.41 mmol) in dichloromethane (20 mL) was added dropwise methanesulfonyl chloride (975.86 mg, 8.56 mmol). The mixture was stirred at 0 C. for 1 hour. The resulting solution was washed with water and the organic phase was dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under vacuum to afford 2-[tert-butoxycarbonyl(methyl)amino]ethyl methanesulfonate (1.29 g, 5.08 mmol) as a colorless oil. LCMS (ESI) [M+H]+=254

At the same time, in my other blogs, there are other synthetic methods of this type of compound, tert-Butyl (2-hydroxyethyl)(methyl)carbamate, and friends who are interested can also refer to it.

Reference:
Patent; Genentech, Inc.; Chan, Bryan; Drobnick, Joy; Gazzard, Lewis; Heffron, Timothy; Liang, Jun; Malhotra, Sushant; Mendonca, Rohan; Rajapaksa, Naomi; Stivala, Craig; Tellis, John; Wang, Weiru; Wei, BinQing; Zhou, Aihe; Cartwright, Matthew W.; Lainchbury, Michael; Gancia, Emanuela; Seward, Eileen; Madin, Andrew; Favor, David; Fong, Kin Chiu; Hu, Yonghan; Good, Andrew; US2018/282282; (2018); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

68524-30-1,Some common heterocyclic compound, 68524-30-1, name is 2-[(Diphenylmethyl)thio]acetamide, molecular formula is C15H15NOS, 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; [0289 ] In this Example, the modafinil intermediate compound benzhydrylthioacetamide was oxidized to produce modafinil according to the processes described herein using various ratios of alcohol to organic acid and various reaction mixture temperatures.[0290] First, benzhydrylthioacetamide (10 g; MW = 257.35; 1.0 eq.), methanol, and acetic acid were charged to a 250 ml_ flask. Hydrogen peroxide (4.3 ml 1.05 eq.) was then charged to the resulting mixture over the course of about 5 minutes. The reaction was allowed to proceed for about 24 hours, with samples periodically taken for HLPC analysis. Several different trials using particular ratios of methanol and acetic acid at particular temperatures were performed. Results are illustrated in Tables 1-7, below.Table 1 : 20 ml_ methanol/20 mL acetic acid; 400CTable 2: 30 mL metha?ol/10 mL acetic acid; 400CTable 3: 35 mL methanol/5 mL acetic acid; 400C Table 4: 39 mL methanol/1 mL acetic acid; 400C [0291] As illustrated in Tables 1-7 above, the processes of the present invention are effective in producing modafinil at high yield and with relatively low sulfone impurity content. Specifically, as illustrated in Table 2, a reaction mixture comprising 30 mL of methanol and 10 mL acetic acid (i.e., methanol and acetic acid are present in the reaction mixture at a ratio of about 3:1 ) with the oxidation reaction proceeding at 400C is particularly effective, producing modafinil at about 96% yield with a sulfone impurity content of about 0.22%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-[(Diphenylmethyl)thio]acetamide, its application will become more common.

Reference:
Patent; MALLINCKRODT INC.; WO2007/70238; (2007); A2;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

1103234-56-5, Adding a certain compound to certain chemical reactions, such as: 1103234-56-5, name is 2,6-Difluoro-3-(propylsulfonamido)benzoic acid, 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 1103234-56-5.

EXAMPLE 4 Propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide (1) A suspension of sulfonamide acid (9) (1.2 eq.) in CH2Cl2 was treated at room temperature with cat. amount of DMF (0.11 eq.). Within 30 min a solution of oxalylchloride (1.30 eq.) in CH2Cl2 was added and the reaction mixture was stirred for 2 h, whereby the corresponding acid chloride was formed. A suspension of aluminium chloride (AlCl3, 4 eq.) in CH2Cl2 was treated at 0 C. with a solution of Cl-phenyl azaindole (8) in CH2Cl2. To the reaction mixture was subsequently added at room temperature the freshly prepared (above described) acid chloride. Stirring at room temperature for 3 h, aqueous work-up and crystallization from THF/heptane provided the title compound (1) as off-white powder in 85% yield. MS (Turbo Spry): 509 (48%), 507 (M+NH4+, 100%), 492 (40%), 490 (M+H+, 84%).

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, 2,6-Difluoro-3-(propylsulfonamido)benzoic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Brumsted, Corey James; Moorlag, Hendrik; Radinov, Roumen Nikolaev; Ren, Yi; Waldmeier, Pius; US2012/22258; (2012); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

550-89-0, 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. 550-89-0, name is Phenazine-1-carboxamide, A new synthetic method of this compound is introduced below.

Synthesis of the specific process: phenazine-1-carboxamide hydrolysis under acidic conditions to produce phenazine-1-carboxylic acid;Take 20mmol of phenazine-1-carboxylic acid (0.4577g) and 200ml of thionyl chloride was added to a 500ml round bottom flask, the installation of a reflux reaction device (using anhydrous calcium chloride drying tube), magnetic stirring, reflux reaction 6h, After cooling, the thionyl chloride was removed by rotary evaporation to obtain the intermediate phenazine-1-carbonyl chloride, which was used for the next reaction without purification;The obtained phenazine-1-carboxylic acid chloride was dissolved in 200ml of dry dichloromethane (DCM), added into a 500ml dry round bottom flask, protected by nitrogen, magnetically stirred, placed in an ice-water bath and cooled, and then 11.15 ml triethylamine (80 mmol, 4 equiv.) and2.367 g of 3-methoxy-1-propylamine(20mmol, 1equiv.) After the addition of ice water bath was removed at room temperature for 14h, intermittent sampling,The reaction was monitored by TLC. After DCM was removed by rotary evaporation, the reaction mixture was extracted three times and extracted with 450 ml of liquid (ethyl acetate and H 2 O in a volume ratio of 2: 1) each time. The combined organic phases were dried over anhydrous sodium sulfate for 12 h, filtered, EA washed the solid sodium sulfate, rotary steam, in order to transform the compoundProduct 15-1, 1.4883 g, 22.93% yield.

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; Hunan Agricultural University; Zhang Ya; Liao Xiaolan; Liu Shuangqing; Xiang Yaqin; (7 pag.)CN106922679; (2017); A;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

16066-84-5, 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. 16066-84-5, name is tert-Butyl methylcarbamate, A new synthetic method of this compound is introduced below.

[00724] Step E: To a stirred solution of (1S,2S,5R)-5-(6-chloro-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)-2-phenoxycyclohexan-1-ol (78 mg, 0.18 mmol) and tert-butyl methylcarbamate (121 mg, 0.92 mmol) in 600 muL of dioxane was added Cs2CO3 (120 mg, 0.37 mmol) followed by 2-Dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (34 mg, 0.074 mmol). The reaction mixture was sparged with argon for 5 minutes and then Pd2(dba)3 (34 mg, 0.037 mmol) was added and the vial was capped and heated to 100 C overnight. The reaction mixture was partitioned between dichloromethane (15 mL) and water (15 mL), extracted 3 x 15 mL with dichloromethane, dried over MgSO4, filtered and concentrated. The residue was purified over silica gel (0% to 75% ethyl acetate in hexanes) to afford tert-butyl (1-((1R,3S,4S)-3-hydroxy-4-phenoxycyclohexyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)(methyl)carbamate (30 mg, 31% yield).

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; ARRAY BIOPHARMA INC.; ALLEN, Shelley; BOYS, Mark Laurence; COOK, Adam; GAUDINO, John; HINKLIN, Ronald Jay; LAIRD, Ellen; MCNULTY, Oren T.; METCALF, Andrew T.; NEWHOUSE, Brad; ROBINSON, John E.; (545 pag.)WO2019/113190; (2019); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

A common heterocyclic compound, 2675-89-0, name is 2-Chloro-N,N-dimethylacetamide, molecular formula is C4H8ClNO, 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. 2675-89-0.

Step 3: 2-[2-(3-Butoxyphenyl)-(tert-butoxycarbonyl)ethylamino]-N,N-dimethylacetamide To a suspension of NaH (60%, 2.0 g, 51 mmol) in dry DMF (125 ml) cooled at 0 C., a solution of 2-(3-butoxyphenyl)-(tert-butoxycarbonyl)ethylamine (7.5 g, 25.5 mmol) in dry DMF (125 ml) was added dropwise. After 1 h at room temperature, 2-chloro-N,N-dimethylacetamide (5.2 ml, 51 mmol) was added and the mixture was stirred for 16 h at room temperature. H2O (10 ml) was added and the solvent was evaporated under reduced pressure. The residue was dissolved in H2O (150 ml) and extracted with CH2Cl2 (2*150 ml). The collected organic phases were dried over Na2SO4, filtered and evaporated. The crude was purified by flash chromatography (petroleum ether/EtOAc 4:6) affording the title compound (7.2 g, 75%) as light yellow oil. 1H NMR (300 MHz, DMSO-d6): delta 7.1 (m, 1H), 6.79-6.71 (m, 3H), 3.97 (t, J=6.0 Hz, 2H), 3.96 (s, 2H), 3.40 (dd, J=8.7 Hz, J=7.2 Hz, 2H), 2.88 (s, 6H), 2.76 (dd, J=7.9 Hz, J=6.4 Hz, 2H), 1.76 (m, 2H), 1.46 (m, 2H), 1.37 (s, 9H), 0.95 (t, J=7.3 Hz, 3H). ESI+MS: calcd for C21H34N2O4: 378.52; found: 379.0 (MH+).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Chloro-N,N-dimethylacetamide, its application will become more common.

Reference:
Patent; NEWRON PHARMACEUTICALS S.P.A.; US2010/210631; (2010); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Some common heterocyclic compound, 3984-14-3, name is N,N-Dimethylsulfamide, molecular formula is C2H8N2O2S, 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. 3984-14-3

To a solution of 4-{[4-chloro-3-(trifluoromethyl)phenoxy]methyl}benzoic acid (Preparation 16, 237 mg, 0.72 mmol) in dichloromethane (8 ml_) was added EDCI (344 mg, 1 .79 mmol) followed by addition of N,N-dimethylsulfamide (222 mg, 1 .79Calculation isn’t correct mmol). The reaction was left to stir at room temperature for 3 hours. A solution of KHSO4 (10ml_) was added and the mixture separated using a phase separation cartridge. The organics were dried in vacuo to yield a white solid as the title compound (285 mg, 97%). 1 NMR (400 MHz, CDCI3): delta 2.95 (s, 6H), 5.10 (s, 2H), 7.00 (dd, 1 H), 7.23 (d, 1 H), 7.36 (d, 1 H), 7.49 (d, 2H), 7.89 (d, 2H). LCMS Rt = 1 .74 minutes MS m/z 406 [M35CI-H]”

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3984-14-3, its application will become more common.

Reference:
Patent; PFIZER LIMITED; RAWSON, David James; STORER, Robert Ian; SWAIN, Nigel Alan; WO2013/88315; (2013); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

360-64-5, 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. 360-64-5, name is 2-(Trifluoromethyl)benzamide belongs to amides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

[Step 2] Ethyl 5-({[2-(Trifluoromethyl)phenyl]carbonyl}amino)-2,3-dihydro-1-benzofuran-7-carboxylate 1,4-dioxane (20 ml) was added to ethyl 5-bromo-2,3-dihydro-1-benzofuran-7-carboxylate (600 mg), 2-(trifluoromethyl)benzamide (501 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (96 mg), cesium carbonate (1.01g) and 140 tris(dibenzylideneacetone)dipalladium (114 mg). After degassing, the mixture was stirred at 100C under argon atmosphere for 24 hours. The reaction mixture was filtered off on celite, the solvent was removed under reduced pressure. The resultant residue was purified on silica gel column chromatography to obtain the titled compound (220 mg) as slightly yellow powder.

The synthetic route of 360-64-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Nippon Shinyaku Co., Ltd.; OTSU, Hironori; EP2746265; (2015); B1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Adding some certain compound to certain chemical reactions, such as: 62009-47-6, name is 2-Aminomalonamide, 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 62009-47-6. 62009-47-6

Diethylaminomalonate Aminomalondiamide 2-Carbamido-3-hydroxypynazine To an aqueous solution of diethylaminomalonate (hydrochloride form) was added sodium hydrogenocarbonate (pH> 7). After extraction, the organic phase was evaporated under reduced pressure and treated with an ammoniacal solution of methanol at 80C overnight to give aminomalondiamide quantitatively. This compound was used for next step without purification and dissolved in water. To that solution was added glyoxal sodium bisulfite hemihydrate, this reaction mixture was stirred at 90C for 3h, and then made basic with 58% NH4OH. Then, 30% H2O2 was added dropwise with rapid stirring to the cold solution (0C) [J. Med. Chem. 1983, 26, 283-86, J. Heterocyclic Chem. 1979, 16, 193]. The reaction mixture was allowed to warm at room temperature and the desired 2-hydroxy-3- carboxamidopyrazine precipitated. The solid was collected (63% yield) and part of it recrystallized.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 2-Aminomalonamide.

Reference:
Patent; IDENIX (CAYMAN) LIMITED; CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE; WO2007/144686; (2007); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics