Month: July 2021

Synthetic Route of 821-10-3, 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. 821-10-3, name is 1,4-Dichlorobut-2-yne belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

1,4-Dichloro-2-butyne (6 mmol, 0.58 mL) was added to the stirred suspension of potassium phthalimide (3 mmol, 0.556 g) in DMF (5 mL), and heated to 100 C for 5 h. After cooling, the reaction mixture was extracted with dichloromethane and water. The organic layers were pooled, dried, and concentrated in vacuo. The residue was purified by column chromatography (hexane/ethyl acetate 1:19) to furnish 0.35 g of 2-(4-chlorobut-2-ynyl)isoindoline-1,3-dione (28) (white solid, yield 50%). 1H NMR (300 MHz, CDCl3) 4.11 (s, 2H), 4.51 (s, 2H), 7.75 (dd, J1 = 3.1, J2 = 5.5, 2H), 7.89 (dd, J1 = 3.1, J2 = 5.4, 2H).13C NMR (75 MHz, CDCl3) delta 27.1, 45.7, 46.9, 51.7 (2C), 54.7 (2C), 78.1, 78.4, 123.4 (2C), 131.9 (2C), 134.0 (2C), 166.9 (2C). 28 was reacted with 1-methylpiperazine following the method described in Section 6.6. to give 2-(4-(4-methylpiperazin-1-yl)but-2-ynyl)isoindoline-1,3-dione (29): A solution of 29 (0.72 mmol, 0.213 g) and hydrazine (0.72 mmol, 0.03 mL) in 1 mL of ethanol was heated at reflux for 2 h. After cooling to 0 C, phthalhydrazide was removed by filtration. Evaporation of the filtrate gave 30 as a free base.

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, 1,4-Dichlorobut-2-yne, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Nguyen, Thuy; Sakasegawa, Yuji; Doh-Ura, Katsumi; Go, Mei-Lin; European Journal of Medicinal Chemistry; vol. 46; 7; (2011); p. 2917 – 2929;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 1008361-80-5, 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. 1008361-80-5, name is 4-Bromo-3-chlorobenzene-1,2-diamine belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 4-bromo-3-chloro-benzene-1,2-diamine (500 mg, 2.26 mmol) in EtOH (20.0 mL), 1,4- dioxane-2,3-diol (380 mg, 3.16 mmol) was added at r.t.. The mixture was stirred at r.t. for 18 h. The reaction mixture was then vacuum-concentrated, and the residue was purified by column chromatography on silica gel (gradient elution, 20 – 40% EtOAc/hexane) to give 6-bromo-5-chloroquinoxaline (269 mg). MS: [M+H] + = 243, 245.

The synthetic route of 4-Bromo-3-chlorobenzene-1,2-diamine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TAIHO PHARMACEUTICAL CO., LTD.; OTSUKA PHARMACEUTICAL CO., LTD.; SHIMAMURA, Tadashi; KATO, Ryo; MIURA, Risako; MITA, Takashi; OGAWA, Takahiro; SAGARA, Yufu; JOHNSON, Christopher Norbert; HOWARD, Steven; DAY, James Edward Harvey; ST. DENIS, Jeffrey David; LIEBESCHUETZ, John Walter; (345 pag.)WO2020/22323; (2020); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 13078-79-0, name is 2-(3-Chlorophenyl)ethanamine, 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. Quality Control of 2-(3-Chlorophenyl)ethanamine

2-(1-isopropyl-6-oxo-3-(pyridin-2-yl)piperidin-3-yl)acetaldehyde44B (0.15 g, 0.58 mmol) was dissolved in dichloromethane (10 mL).(3-chlorobenzyl)methylamine is sequentially added thereto(0.098g, 0.69mmol), triethylamine(0.070 g, 0.69 mmol), anhydrous sodium sulfate (0.56 g).After reacting at room temperature overnight, sodium borohydride (0.035 g, 0.86 mmol) was added.Stirring was continued for 2 h, water (20 mL) was added andEtOAc was appliedThe organic phases were combined and washed with a saturated aqueous solution of brine (30 mL×1).Dry over anhydrous sodium sulfate, filter, and concentrate the filtrate.Column chromatography (dichloromethane/methanol = 30:1)Light yellow oily product 5-(2-((3-chlorobenzyl)amino)ethyl)-1-isopropyl-5-(pyridin-2-yl)piperidin-2-one (45A)(0.085 g, 45%).

The synthetic route of 2-(3-Chlorophenyl)ethanamine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sichuan Hai Sike Pharmaceutical Co., Ltd.; Fan Jiang; Zhu Fengfei; Chen Qingping; Wang Chengtao; (251 pag.)CN109206417; (2019); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 104-11-0, name is 1-(4-Chlorophenyl)-N-methylmethanamine, belongs to chlorides-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 104-11-0, Recommanded Product: 1-(4-Chlorophenyl)-N-methylmethanamine

In a 25 mL single neck round-bottomed flask, the intermediate 4 (1 g, 3.35 mmol) from Example 1 and N-(4-chlorobenzyl)-N-methylamine (2.6 g, 16.7 mmol) were added and the mixture was heated to 120 C for 24 h. Reaction was monitored by TLC to completion and was added 10 mL water followed by acidification with dil. HCl to pH 3-4. The mixture was extracted with EtOAc (3 X 50 mL) and the combined organic layer was dried over Na2S04. The sovent was evaporated under reduced pressure to obtain the crude product which was purified by column chromatography (silica gel) to provide the desired product, 7-((4-chlorobenzyl)(methyl)amino)-6-fluoro-l-isobutyl-4-oxo-l ,4-dihydroquinoline-3- carboxylic acid (5), 50 mg; Yield (3.5 %); H NMR (400 MHz, OMSO-de) : delta 15.44 (s, 1H), 6.84-8.70 (m, 7H), 4.66 (s, 2H), 4.24-4.25 (d, 2H), 3.14 (s, 3H), 1.81-1.87 (m, 1H), 0.75-0.77 (d, 6H); MS (ESI): 417.2(M+H); HPLC: 96.35 %.

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

Reference:
Patent; NIROGYONE THERAPEUTICS, INC.; SANDANAYAKA, Vincent; WU, Qiong; (80 pag.)WO2016/81464; (2016); A1;,
Chloride – Wikipedia,
Chlorides – 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 13918-92-8 as follows. Recommanded Product: 13918-92-8

General procedure: To 5-(5-(5-Aminopyridin-3-yl)thiophen-2-yl)-2-methyl- isoindolin-1-one (49) (225 mg, 0.79 mmol) in dry pyridine (23 mL) under N2 at RT,was added dropwise, 2,4-difluorobenzenesulphonyl chloride (336 mg, 1.58 mmol) in CH2Cl2(3 mL) over 5 min. The suspension was heated to 45 C under N2 for 4 h., at which pointanother portion of 2,4-difluorobenzenesulphonyl chloride (169 mg, 0.79 mmol) in CH2Cl2 (2mL) was added. The whole mixture was left to stir for at 45 C under N2 for 16 h., then thesolvent removed under reduced pressure. The resulting residue was suspended in acetone (10mL), 1 M HCl (20 mL) added, and the entire mixture stirred for 10 minutes. The solid wasthen collected by filtration, washed well with 1 M HCl and water, dried, and purified bychromatography as described below. In cases where the bis-sulphonamide was also formed, a second step was introduced wherethe crude product above was treated with a 1:1 mixture of 1,4-dioxane and 2 M NaOH. Thecrude sulphonamide resulting from subsequent acidification of the reaction mixture wasisolated by filtration, washed well with water, and dried. Purification was carried out by flashcolumn chromatography (2% MeOH/CH2Cl2 as eluant), giving the title compound as a paleyellow solid (211 mg, 545).

According to the analysis of related databases, 13918-92-8, the application of this compound in the production field has become more and more popular.

Reference:
Article; Spicer, Julie A.; Miller, Christian K.; O’Connor, Patrick D.; Jose, Jiney; Huttunen, Kristiina M.; Jaiswal, Jagdish K.; Denny, William A.; Akhlaghi, Hedieh; Browne, Kylie A.; Trapani, Joseph A.; Bioorganic and Medicinal Chemistry Letters; vol. 27; 4; (2017); p. 1050 – 1054;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

39226-96-5, name is (2-Chloro-3-(trifluoromethyl)phenyl)methanamine, belongs to chlorides-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. Recommanded Product: 39226-96-5

Example 12 lambda/-{[2-Chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-1-(3- pyridinyl)-4-imidazolidinecarboxamide (E12); A mixture of crude 3-methyl-2-oxo-1-(3-pyridinyl)-4-imidazolidinecarboxylic acid (0.8 mmol), 1-hydroxybenzotriazole hydrate (147 mg, 0.96 mmol), 1-ethyl-3-(3- dimethylaminopropyl)carbodiimide hydrochloride (184 mg, 0.96 mmol), and N-ethyl morpholine (0.307 ml, 2.4 mmol) in dichloromethane (15 ml) was stirred at room temperature for 10 minutes. A solution of {[2-chloro-3-(trifluoromethyl)phenyl]methyl}amine (168 mg, 0.8 mmol) in dichloromethane (1 ml) was added and the reaction stirred at room temperature for 4 hours. The mixture was partitioned between dichloromethane and saturated sodium hydrogen carbonate solution. The organic phase was separated, washed with water and brine, dried and evaporated. The residue was purified by mass-directed automated HPLC. The solid was dissolved in methanol (5 ml) and anhydrous HCI in ether (1 M, 0.5 ml) was added and the solution was evaporated. The resulting solid was collected, washed with ether and dried to give a pale yellow solid. The solid was dissolved in methanol and applied to a SCX ion exchange cartridge and washed with methanol and then 2M ammonia in methanol. The basic fractions were combined and evaporated and the resulting residue was triturated with ether, collected and dried to give lambda/-{[2-Chloro-3- (trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-1-(3-pyridinyl)-4- imidazolidinecarboxamide (27 mg, 8%). LC/MS [M+H]+ = 413, retention time = 1.96 minutes.

The synthetic route of 39226-96-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXO GROUP LIMITED; WO2008/119825; (2008); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 1005-56-7,Some common heterocyclic compound, 1005-56-7, name is O-Phenyl carbonochloridothioate, molecular formula is C7H5ClOS, 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.

95) 8-Bromo-2′-phenoxythiocarbonyladenosine-3′,5′-cyclic boranophosphate, Sp- isomer (Sp-8-Br-2′-PTC-cAMPB. No. 306)A solution of 5 muiotatauiotaomicronIota of Sp-8-Br-cAMPB (example 2) in 2 ml of dry dichloromethane was treated with 2.5 mg of dimethylaminopyridine (Aldrich) and 1 .4 muIota of phenoxythiocarbonyl chloride (Fluka) for 16 h at RT under argon. The decrease of the starting material at 1 :62 min was followed by HPLC (RP-18, 20 Vol.-% acetonitrile, 20 mM triethylammonium formate buffer, 1 .5 ml/min., pH 7 at 259 nm).The peak for Sp-8-Br-2′-PTC-cAMPB at 2:69 min was isolated by semipreparative column chromatography on reversed phase silica (RP-18, 40 Vol.-% acetonitrile, 20 mM triethylammonium formate buffer, 1 .5 ml/min., pH 7), yield 87.6%.C17H18BBrN506PS; MW 542.1 1 UV: max: 259 nm HPLC: 2:69 min.ESI-MS (+): m/z 643/645 [M + 2TEA + H] +^ 629 [M + 2TEA – BH3 + H] + ESI-MS (-): m/z 540/542 [M – H]? 526 [M – BH3 – H] ~ ^ 212 [8-Br-A – H] +

The synthetic route of 1005-56-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BIOLOG LIFE SCIENCE INSTITUTE FORSCHUNGSLABOR UND BIOCHEMICA-VERTRIEB GMBH; GENIESER, Hans-Gottfried; WO2012/130829; (2012); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 108-37-2, 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. 108-37-2, name is 1-Bromo-3-chlorobenzene, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of diisopropylamine (76 mL, 0.4 mol) in anhydrous THF (664 mL) and n-hexane (220 mL) was added 2.5 M n-BuLi (160 mL, 0.4 mol) dropwise at -78 0C over 1 h. The mixture was stirred for 1 h at -78 0C and a solution of 1-bromo- 3-chlorobenzene (76 g, 0.4 mol) in anhydrous THF (300 mL) was added dropwise at – 78 0C. After stirring for an additional 1 h at the same temperature, a solution of iodine (101 g, 0.4 mol) in anhydrous THF (400 mL) was added dropwise at -78 0C. The temperature was raised from -78 0C to rt during 2 h. After stirring for 18 h at rt, the mixture was concentrated in vacuo to give the crude product (120 g) which was distilled under reduced pressure to give l-bromo-3-fluoro-2-iodobenzene (115 g, 91%). 1H NMR (400MHz, CDCl3): 7.12-7.18 (t, IH), 7.35-7.41 (dd, IH), 7.49-7.54 (dd, IH); MS (E/Z): 317 (M+H+)

The chemical industry reduces the impact on the environment during synthesis 1-Bromo-3-chlorobenzene. I believe this compound will play a more active role in future production and life.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; VITAE PHARMACEUTICALS, INC.; WO2008/124575; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 53531-69-4, 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. 53531-69-4 name is (4-Bromophenyl)methanesulfonyl chloride, 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 stirred solution of (4-bromophenyl)methanesulfonyl chloride (DC; 500 mg, 1.85 mmol) in pyridine (10 mL) under inert atmosphere was added morpholine (712 mg, 2.22 mmol) at RT and stirred for 16 h. The reaction was monitored by TLC. After complete consumption of the starting material, the reaction mixture was diluted with water (30 mL) and was extracted with EtOAc (2×20 mL). The combined organic extracts were washed with water (15 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified by silica gel column chromatography (20-30% EtOAc/hexanes) to afford DD (360 mg, 61%) as a white solid. *H NMR (400 MHz, CDC13): delta 7.53 (d, J = 8.8 Hz, 2H), 7.29 (d, / = 8.8 Hz, 2H), 4.16 (s, 2H), 3.65 (t, / = 4.8 Hz, 4H), 3.13 (t, 7 = 4.8 Hz, 4H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, (4-Bromophenyl)methanesulfonyl chloride, and friends who are interested can also refer to it.

Reference:
Patent; VIAMET PHARMACEUTICALS, INC.; HOEKSTRA, William, J.; YATES, Christopher, M.; RAFFERTY, Stephen, W.; WO2014/117090; (2014); A1;,
Chloride – Wikipedia,
Chlorides – 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 1939-99-7 as follows. Recommanded Product: 1939-99-7

Example 95 Preparation of t-Butyl (3-Benzylsufonylamino-6-methyl-2-oxo-1,2-dihydro-1-pyridyl)acetate STR115 Collidine (0.59 mL, 4.5 mmole) was added in one portion to a stirred solution of the compound of Example 94 (0.89 g, 3.7 mmole) and benzylsulfonyl chloride (0.86 g, 4.5 mmole) in acetonitrile (20 ml) cooled in an ice bath. The solution was stirred for 5 minutes at 0 C., followed by 45 min at room temperature. The reaction mixture was quenched with water, then diluted with ethyl acetate (100 mL), washed with 3% HCl (until aqueous layer is pH 1), and brine, dried over magnesium sulfate, and the solvent was removed. The residue was dissolved in methanol, concentrated to a volume of approximately 3 mL, and the product was precipitated with the addition of diethyl ether. The precipitate was filtered to give 0.67 g of the title compound. The filtrate was concentrated and chromatographed on flash silica gel using 20-67% ethyl acetate hexanes as eluent. An additional 0.20 g of the title compound was recovered. A total of 0.87 g of the title compound (59% yield) was recovered. Rf=0.29 (silica gel, 33% ethyl acetate/hexanes).

According to the analysis of related databases, 1939-99-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Corvas International, Inc.; US5658930; (1997); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics