Author: Jessica.F

Some common heterocyclic compound, 15205-11-5, name is 2-Chloro-4-fluorobenzylamine, molecular formula is C7H7ClFN, 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. name: 2-Chloro-4-fluorobenzylamine

Example 82; /V-[(2-chloro-4-fluorophenyl)methyl]-2-[3,5-dimethyl-1-(2-phenylethyl)- 1H-pyrazol-4-yl]acetamide (E82)[3,5-dimethyl-1-(2-phenylethyl)-1 H-pyrazol-4-yl]acetic acid (0.63 mmol) was dissolved in dimethylformamide (2 ml) and to this was added O-(7-Azabenzotriazol- 1-yl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate (HATU, 0.63 mmol) and diisopropylethylamine (DIPEA, 1.26 mmol). The mixture was left to stand at room temperature for 15-20 minutes and then [(2-chloro-4-fluorophenyl)methyl]amine (0.63 mmol) in dimethylformamide (1 ml) was added. The mixture was left to stand overnight at room temperature and then the solvents were evaporated in-vacuo. The residue was partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate. The mixture was then filtered through a phase separator and the organic phase was evaporated to give the crude product. The crude material was purified by mass-directed automated HPLC to give the title compound as product after lyophilisation of the combined product fractions. LC/MS [M+H]+ = 399, retention time = 3.16 minutes.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 15205-11-5, its application will become more common.

Reference:
Patent; GLAXO GROUP LIMITED; WO2008/138876; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 13726-14-2, A common heterocyclic compound, 13726-14-2, name is 4-Chloro-3-methoxyaniline, molecular formula is C7H8ClNO, 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.

General procedure: Procedure B: A mixture of substituted 2,4-dichloropyrimidine (1.0 equiv.), and substituted aniline (1.0-1.05 equiv.), and DIPEA (1.2 equiv.) in isopropanol (0.1 M) was stirred and heated at reflux. The reaction time, work-up, and product isolation procedure are described below.

The synthetic route of 13726-14-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.; SCHOeNBRUNN, Ernst; LAWRENCE, Nicholas, J.; LAWRENCE, Harshani, R.; (257 pag.)WO2016/22460; (2016); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 2106-02-7, name is 2-Chloro-4-fluoroaniline, 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. Product Details of 2106-02-7

Into a 20-L 4-neck round flask was placed a solution of 2-chloro-4- fluorobenzenamine (1300 g, 8.82 mol, 1.00 equiv, 99%) in toluene (10 L), 4- methylbenzenesulfonic acid (3.1 g, 17.84 mmol, 99%), and hexane-2,5-dione (1222.5 g, 10.62 mol, 1.20 equiv, 99%). The resulting solution was heated to reflux for 1 h in an oil bath and cooled. The pH value of the solution was adjusted to 8 with sodium carbonate (1 mol/L). The resulting mixture was washed with 1×5000 mL of water and concentrated under vacuum. The crude product was purified by distillation and the fraction was collected at 140 0C to afford l-(2- chloro-4-fluorophenyl)-2,5-dimethyl-lH-pyrrole (1700 g, yield: 85%).

The synthetic route of 2-Chloro-4-fluoroaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ARRAY BIOPHARMA INC.; GENENTECH, INC.; ALIAGAS, Ignacio; GRADL, Stefan; GUNZNER, Janet; MATHIEU, Simon; RUDOLPH, Joachim; WEN, Zhaoyang; WENGLOWSKY, Steven Mark; WO2011/25947; (2011); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 50594-82-6,Some common heterocyclic compound, 50594-82-6, name is 3,4,5-Trichlorobenzotrifluoride, molecular formula is C7H2Cl3F3, 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.

PRODUCTION EXAMPLE 3 (Production of Compound No. (3)) After 44 mg (1.1 mmol) of 60% sodium hydride was added to a solution of 0.14 g (1 mmol) of 5-(1-methylcyclopropyl)-1,3,4-oxadiazolin-2-one in 5 ml of N,N-dimethylformamide at room temperature, the mixture was stirred at the same temperature for 15 minutes. To the mixture was added 0.25 g (1 mmol) of 3,4,5-trichlorobenzotrifluoride followed by heating a 80 C. for 6 hours. After cooling, the mixture was poured into water and extracted with ethyl acetate. After drying over magnesium sulfate, the extract was concentrated under reduced pressure to give the crude product. The crude product was subjected to silica gel column chromatography to give 35 mg of 5-(1-methylcyclopropyl)-3-(2,6-dichloro-4-trifluoromethylphenyl)-1,3,4-oxadiazoline-2-one. m.p. 107.1 C.

The synthetic route of 50594-82-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sumitomo Chemical Company, Limited; US5124341; (1992); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 6276-54-6, A common heterocyclic compound, 6276-54-6, name is 3-Chloropropan-1-amine hydrochloride, molecular formula is C3H9Cl2N, 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 the 3 mL of dichloromethane was added the compound of Example 5 (65 mg, 0.12 mmol)After dissolving 3-chloropropylamine hydrochloride (33 mg, 0.24 mmol) and triethylamine (0.05 mL, 0.37 mmol)And the mixture was stirred at room temperature under a nitrogen atmosphere for 5 hours.After completion of the reaction, Dichloromethane and purified water were added and stirred,The organic layer and the water layer were separated,The water layer was extracted three times with dichloromethane to collect all organic layers.After the water remaining in the organic was removed with magnesium sulfate, Concentrated and purified by silica gel column chromatography (eluent: 5% MeOH-CH2Cl2) to obtain the desired compound as a white solid. (49 mg, 78.6%).

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; BioActs Co., Ltd.; Park, Jin Woo; Choi, Jae-Ho; Kim, Ki Won; Kim, Jinju; (29 pag.)KR2017/60859; (2017); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 93-50-5, 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. 93-50-5, name is 4-Chloro-2-methoxyaniline, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of 6,8-dichloro-4-oxo-chromene-2-carboxylic acid (Int-2, 1.3 g, 5.02 mmol) in DCM (20 mL) was added 4-chloro-2-methoxyaniline (949 mg, 6.02 mmol), DIPEA (1.15 g, 8.9 mmol) and HATU (3.3 g, 8.9 mmol) at room temperature and the resulting mixture was then stirred at room temperature for 18 hours. After the reaction was completed, the mixture was diluted with water (30 mL) and extracted with EtOAc (50 mL) three times. The combined organic layer was washed with brine, dried over anhydrous Na2S04 and concentrated in vacuo. The residue was purified by silica gel flash chromatography (elution with PE/EtOAc=lO: 1-1:4) to give 6,8-dichloro-N-(4-chloro-2-methoxyphenyl)-4-oxo-chromene-2-carboxamide (1.6 g, 80 %) as a yellow solid. MS obsd. (ESP) [(M+H)+]: 398.1.

The chemical industry reduces the impact on the environment during synthesis 4-Chloro-2-methoxyaniline. I believe this compound will play a more active role in future production and life.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; FENG, Song; LIANG, Chungen; LIU, Yongfu; TAN, Xuefei; WU, Jun; WANG, Jianping; (134 pag.)WO2020/79106; (2020); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 1435-48-9, A common heterocyclic compound, 1435-48-9, name is 2,4-Dichloro-1-fluorobenzene, molecular formula is C6H3Cl2F, 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.

Reference Example 2-44 2,4-Dichloro-5-fluorobenzoic acid Following the procedure described in Reference Example 2-25, the title compound was prepared from 2,4-dichloro-1-fluorobenzene (66% yield). NMR (CDCl3) delta: 7.59 (1H, d, J=6.2 Hz), 7.85 (1H, d, J=8.8 Hz), 8.28 (1H, br s).

The synthetic route of 1435-48-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Uchikawa, Osamu; Mitsui, Keita; Asakawa, Akiko; Morimoto, Shigeru; Yamamoto, Masataka; Kimura, Hiroyuki; Moriya, Takeo; Mizuno, Masahiro; US2003/187014; (2003); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 118-69-4, name is 2,6-Dichlorotoluene, 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 118-69-4, Computed Properties of C7H6Cl2

EXAMPLE 1-1 Preparation of 2,4-dichloro-3-methylbromobenzene To a solution of 48.8 g (0.3 mol) of 2,6-dichlorotoluene in 60 ml of carbon tetrachloride, 0.7 g of iron powder and 0.1 g of iodine were added. Then, 52.8 g (0.33 mol) of bromine was dropwise added thereto at room temperature while maintaining the reaction temperature at a level of from 22 to 25 C. After completion of the dropwise addition, the reaction was continued at the same temperature until generation of hydrogen bromide ceased. After the reaction, the reaction solution was added to 300 ml of ice water and extracted with 300 ml of 1,2-dichloroethane. The organic layer was separated and washed sequentially with water, a saturated sodium hydrogen sulfite aqueous solution, water and a saturated sodium chloride aqueous solution. Then, the solvent was distilled off under reduced pressure to obtain 71.9 g (yield: 99.5%) of desired 2,4-dichloro-3-methylbromobenzene. Melting point: 32-33 C.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2,6-Dichlorotoluene, and friends who are interested can also refer to it.

Reference:
Patent; Nissan Chemical Industries Ltd.; US4942246; (1990); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 67279-24-7, 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. 67279-24-7 name is 1,4-Dichloro-5,6,7,8-tetrahydrophthalazine, 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 1,4-dichloro-5,6,7,8-tetrahydro-phthalazine (compound 25, 100 mg, 0.492 mmol) in NMP (3 mL) is added 1-[5-trifluoromethyl)-pyrid-2-yl)-piperazine (114 mg, 0.492 mmol) followed by triethyl amine (218 muL, 1.57 mmol). The mixture was heated in a microwave reactor for 140 C. for 60 min. Water was added to the reaction mixture and extracted with EtOAc. The combined arganic extracts were washed with water, brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel (EtOAc/heptane 10% to 70%) to yield 96 mg (49%) of the title compound.1H NMR (400 MHz, CD2Cl2) delta=8.41 (s, 1H), 7.73 (dd, J=9.0 Hz, 2.5 Hz, 1H), 6.79 (d, J=9.0 Hz, 1H), 3.85 (m, 4H), 3.40 (m, 4H), 2.76-2.68 (m, 4H), 1.93 (m, 2H), 1.80 (m, 2H).HR MS (m/z, MH+) meas. 398.1359.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1,4-Dichloro-5,6,7,8-tetrahydrophthalazine, and friends who are interested can also refer to it.

Reference:
Patent; Novartis AG; US2010/41663; (2010); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Some common heterocyclic compound, 50594-82-6, name is 3,4,5-Trichlorobenzotrifluoride, molecular formula is C7H2Cl3F3, 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. Formula: C7H2Cl3F3

Comparative Example 1 : Preparation of 2,6-dichloro-4-(trifluoromethyl) phenylhydrazine of the formula 1-1 from 3,4,5-trichloro- benzotrifluoride in tetrahydrofurane; 10 g (40 mmole) of 3,4,5-trichlorobenzotrifluoride (99.7% purity) were dissolved in 30 g (417 mmole) of tetrahydrofurane. To this solution were added 8 g (160 mmole) of hydrazine hydrate (100%). The resulting mixture was stirred at 500C for 24 hours. Thereafter, an organic phase of 40.7 g was separated. The solution obtained by this separation contained the product 2,6-dichloro-4-(trifluoromethyl)phenylhydrazine in an amount of 0.9 wt-% and the starting material 3,4,5-trichlorobenzotrifluoride in an amount of 27.1 wt-%, meaning that a product yield not higher than 3.7 % was obtained.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 50594-82-6, its application will become more common.

Reference:
Patent; BASF SE; WO2008/113661; (2008); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics