Category: chlorides-buliding-blocks

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. 90390-33-3, name is 3-Chloro-5-fluorobenzylamine, A new synthetic method of this compound is introduced below., Formula: C7H7ClFN

A solution of ethyl 2-oxopyrrolidine-3-carboxylate (180.00 g, 929.61 mmol) and (3-chloro-5-fluoro-phenyl) methanamine (148.36 g, 929.61 mmol) in xylene (4.00 L) is heated to 130 for 16 hours. The reaction mixture is cooled to 10 and a solid precipitates after 30 minutes. The suspension is filtered and the filter cake is washed with xylene (3×500 mL) , petroleum ether (2×500 mL) and dried in vacuum to give the title product (81 g) . The filtrates are concentrated under reduced pressure and the residue in xylene (3 L) is heated to 130 for 40 hours. The reaction mixture is cooled to 10 and solid precipitates after 30 minutes. The suspension is filtered and the filter cake is washed with xylene (2×500 mL) , petroleum ether (2×500 mL) , and dried in vacuum to give the title product (81.38 g) . The combined product (164.38 g, 607.26 mmol, 65.32) is obtained as a white solid. ES/MS m/z 270.9 (M+H) .

The synthetic route of 90390-33-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELI LILLY AND COMPANY; LILLY CHINA RESEARCH AND DEVELOPMENT CO., LTD.; HO, Koc Kan; QUAN, Weiguo; ZHOU, Jingye; (38 pag.)WO2017/5069; (2017); A1;,
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Application of 69411-05-8,Some common heterocyclic compound, 69411-05-8, name is 3-Chloro-5-trifluoromethylaniline, molecular formula is C7H5ClF3N, 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: To a solution of 3-chloroaniline 5a (37mg, 0.33mmol) in H2O (10mL cooled to-5C) was added 0.2mL of 2N HCl (aq.). To the resulting acidic aniline solution, 1N solution of sodium nitrite (0.33mL, 0.33mmol) was added dropwise to generate the aryldiazonium salt solution 6a. To the aryldiazonium salt solution was added sodium acetate (54mg, 0.66mmol), followed by 1mL solution of crude 3-oxo-3-(3-phenylisoxazol-5-yl)propanenitrile 4a (88mg, 0.33mmol) in ethanol. The reaction mixture was stirred at 0C for 5min, and then poured onto H2O (10mL) and extracted with ethyl acetate (20mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by short column chromatography on silica gel, eluting with hexane/ethyl acetate (2/1) to provide the desired product 7 (67mg, 50% for two steps from 3a) as a yellow solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Chloro-5-trifluoromethylaniline, its application will become more common.

Reference:
Article; Ye, Na; Zhu, Yingmin; Liu, Zhiqing; Mei, Fang C.; Chen, Haiying; Wang, Pingyuan; Cheng, Xiaodong; Zhou, Jia; European Journal of Medicinal Chemistry; vol. 134; (2017); p. 62 – 71;,
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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. 129482-45-7, name is 4-Benzyl-2-(chloromethyl)homomorpholine, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C13H18ClNO

EXAMPLE 54 (4-Benzyl-1,4-oxazepan-2-ylmethyl)-phenyl amine 80 Aniline (2.59 mL, 28.4 mmol) and NaI (4.06 g, 27.1 mmol) were added to a solution of 4-benzyl-2-chloromethyl-1,4-oxazepane (79) (6.49 g, 27.1 mmol) in n-butanol (68 mL, 0.4 M), and the reaction was heated to 110 C. until the reaction was judged complete by TLC (4 h). The reaction was cooled to room temperature, and water and CH2Cl2 were added. The organic layer was removed, and the aqueous layer was extracted with CH2Cl2 (2*). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo to achieve (4-benzyl-1,4-oxazepan-2-ylmethyl)-phenyl amine 80, which was used without purification in the next reaction. 1H NMR (partial, CDCl3) 4.08-3.86 (3H, m), 3.80 (1H, d, J=13.3 Hz), 3.73 (1H, d, J=13.3 Hz), 3.22-3.05 (2H, m), 2.95-2.70 (3H, m), 2.64 (1H, dd, J=13.6, 7.6 Hz), 2.1-1.9 (2H, m) ppm. 13C NMR (CDCl3) 148.33, 139.38, 129.28, 129.11, 128.46, 127.23, 117.44, 113.13, 76.70, 67.49, 62.92, 59.35, 54.76, 46.93, 30.75 ppm. LRMS: 296.68.

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 129482-45-7.

Reference:
Patent; Sepracor Inc.; US6635661; (2003); B2;,
Chloride – Wikipedia,
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Adding a certain compound to certain chemical reactions, such as: 202865-57-4, name is 1-Bromo-2,5-dichloro-3-fluorobenzene, 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 202865-57-4, HPLC of Formula: C6H2BrCl2F

A mixture of 1-bromo-2,5-dichloro-3-fluorobenzene (0.50 g, 2.050 mmol), tert-butyl (0564) hydrazinecarboxylate (0.325 g, 2.460 mmol), palladium(II) acetate (9.21 mg, 0.041 mmol), xantphos (0.024 g, 0.041 mmol) and sodium tert-butoxide (0.296 g, 3.08 mmol) in toluene (4 mL) was degassed and then heated under microwave irridiation at 110 C for 1 h. The reaction mixture was loaded onto a silica gel flash column via a solid cartridge, eluting with 0-30% EtOAc in hexane to afford tert-butyl 2-(2,5-dichloro-3- fluorophenyl)hydrazine-1-carboxylate (118 mg, 0.400 mmol, 19.50 % yield) as a tan solid. MS (ESI) m/z: 238.8 [M-C4H9+H]+; 1H NMR (400 MHz, chloroform-d) delta 6.74-6.78 (m, 1H), 6.70 (dd, J=2.31, 8.47 Hz, 1H), 6.42 (br s, 1H), 6.30 (s, 1H), 1.48 (br s, 9H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Bromo-2,5-dichloro-3-fluorobenzene, and friends who are interested can also refer to it.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; JALAGAM, Prasada Rao; NAIR, Satheesh Kesavan; PANDA, Manoranjan; FENG, Jianxin; WANG, Wei; LIU, Chunjian; ELLSWORTH, Bruce A.; SARABU, Ramakanth; SWIDORSKI, Jacob; HARTZ, Richard, A.; XU, Li; YOON, David S.; BENO, Brett R.; REGUEIRO-REN, Alicia; (457 pag.)WO2019/67702; (2019); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 179897-90-6, A common heterocyclic compound, 179897-90-6, name is 1,3-Dibromo-2-chloro-5-fluorobenzene, molecular formula is C6H2Br2ClF, 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.

EXAMPLE 185 6-(3-Bromo-2-chloro-5-fluorophenyl)-1,2-dihydro-2,2,4-trimethylquinoline (Compound 285, structure 4 of Scheme II, where R1 =3-bromo-2-chloro-5-fluorophenyl) This compound was prepared according to General Method 2 (EXAMPLE 9) from Compound 9 (143.3 mg, 0.45 mmol) and 1-chloro-2,6-dibromo-4-fluorobenzene (129.9 mg, 0.45 mmol). The crude material was purified by flash column chromatography (50 mL silica, hexane) followed by reverse phase preparatory TLC (1000 mL ODS, 80% methanol/water) to afford 4.3 mg (3%) of Compound 285. Data for Compound 285: 1 H NMR (400 MHz, acetone-d6) 7.50 (dd, J=7.8, 3.0, 1H), 7.19 (dd, J=9.2, 3.0, 1H), 7.10 (d, J=2.0, 1H), 7.03 (dd, J=8.1, 2.0, 1H), 6.55 (d, J=8.3, 1H), 5.61 (s, 1H), 5.37 (s, 1H), 1.97 (s, 3H), 1.29 (s, 6H).

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; Ligand Pharmaceuticals Incorporated; US5688810; (1997); A;; ; Patent; Ligand Pharmaceuticals Incorporated; US5696127; (1997); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 67330-62-5, 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 67330-62-5 as follows.

Example 4Synthesis of M-MIPACDEAIn a 5 litre flanged reaction vessel were placed a mixture of 137 ml of sulphuric acid, 580 ml water and 313 ml propan-2-ol. To this were added 250 grams of 3-chloro-2,6-diethylaniline and 203 grams of 2-methyl-6-isopropylaniline. The flask was provided with a stirrer, dropping funnel and condenser and the temperature was raised to 60 C.Formalin solution (35% w/w), 120 ml, was added over a period of 1 hour and heating was subsequently continued for 5 hours. The vessel contents were cooled and neutralised with ammonia solution.The product was extracted into ethyl acetate, washed with water, dried over sodium sulphate, filtered and rotary evaporated to give 467 grams of an amber liquid.Analysis by HPLC showed that the desired hybrid methylene bis-aniline M-MIPACDEA is present at 63% of the total, together with 15% of M-MIPA and 21% of M-CDEA.The liquid showed no sign of crystallisation over 3 months.

According to the analysis of related databases, 67330-62-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; HEXCEL COMPOSITES LIMITED; US2012/316262; (2012); A1;,
Chloride – Wikipedia,
Chlorides – 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. 17601-75-1, name is 2,4-Dichloro-5-methylaniline, A new synthetic method of this compound is introduced below., Quality Control of 2,4-Dichloro-5-methylaniline

Comparative Example 2-11-(2′,2′,2′-Trichloroethyl)-2,4-dichloro-5-methylbenzene; At room temperature, 7.04 g [0.04 mol] of 2,4-dichloro-5-methylaniline are introduced into 28 ml of conc. hydrochloric acid, the mixture is cooled to -5 to 0 C. and a solution, cooled to 0 C., of 3.31 g [0.048 mol] of NaNO2 in 80 ml of water is added dropwise within 60 minutes. Subsequently, the mixture is stirred at -5 to 0 C. for 15 minutes. Subsequently, 3.23 g [0.024 mol] of copper(II) chloride are added. To this mixture is added dropwise, at 0 C. within 30 minutes, a solution of 38.8 g [0.4 mol=10 molar equivalents] of vinylidene chloride in 130 ml of acetone. The mixture is allowed to come to room temperature with good stirring and left to react for another 3 hours. The reaction mixture is diluted with 100 ml of water and extracted twice with 70 ml each time of MTBE. The combined organic phases are washed with 30 ml of water, dried over sodium sulphate and concentrated under reduced pressure. This gives 12.3 g of oil which, according to GC-MS, contains 64.05 area % of 1-(2′,2′,2′-trichloroethyl)-2,4-dichloro-5-methylbenzene. This corresponds to a yield of 67.4% of theory.The GC-MS shows, as by-products, 5.7 area % of Sandmeyer product and 23.8 area % of 1,5-dichloro-2-methyl-4-(2′,2′,4′,4′,4′-pentachlorobutyl)benzene.

The synthetic route of 17601-75-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Bayer CropScience AG; US2010/234651; (2010); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 2770-01-6, 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. 2770-01-6, name is 4-Chloro-1H-imidazo[4,5-c]pyridine belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

The chiral cyclopentenyl moiety 5 (below) was prepared from D-ribose in 8 steps following a previously reported synthetic method via a chiral induction, a regioselective protection of hydroxy group and ring-closing metathesis with 0.1 mole% of the 2nd generation Grubbs catalyst as key steps. 10; The other key intermediate 7 was synthesized according to the previously reported procedure11 from commercially available 4-amino-2-chloropyridine (6) in 4 steps (overall 54% yield) as shown in Scheme 1. Mitsunobu reaction of 7 with 5 provided a mixture of the N9- and N7-regioisomers (8:9 = 2:1) in 94% yield. The separation of the desired product (8) from the reaction mixture was difficult by silica gel column [isolated yields: 20% (8) and 20% (9), respectively]. The ratio of the two isomers was determined by 1H-NMR, and their configuration was identified by Nuclear Overhouser Effect (ID-NOE), which indicated the interaction between the C1 ‘-H and the aromatic C3-H of compound 8, whereas the same effect was not present in compound 9.

The synthetic route of 4-Chloro-1H-imidazo[4,5-c]pyridine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.; WO2007/47793; (2007); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 1009102-44-6, A common heterocyclic compound, 1009102-44-6, name is 1-(4-Chlorophenyl)cyclopropanamine hydrochloride, molecular formula is C9H11Cl2N, 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.

l-(4-chlorophenyl)cyclopropanamine hydrochloride (25 mg, 0.123 mmol) was added to a stirring solution of HATU (59 mg, 0.154 mmol), DIEA (54 mu, 0.308 mmol), and 3-(2-(4-fluorophenyl)-3- (methylcarbamoyl)benzofuran-5-yl)benzoic acid (40 mg, 0.103 mmol) in DMF (1 mL) at rt. It was allowed to stir for 1 hour. The mixture was diluted with EtOAc and washed with sat NaHC03, and sat NaCl. The organic phase was dried over Na2S04, filtered and concentrated and was purified by preparative reverse phase HPLC on a C18 column using a suitably buffered H20/CH3CN gradient, and concentrated to give the titled compound (8 mg, 14%). 1H NMR (500 MHz, DMSO-d6) d ppm 9.37 (1 H, s), 8.46 – 8.55 (1 H, m), 8.22 (1 H, s), 7.95 – 8.05 (2 H, m), 7.86 – 7.95 (3 H, m), 7.74 – 7.83 (2 H, m), 7.59 (1 H, t, J=7.63 Hz), 7.38 – 7.44 (2 H, m), 7.30 – 7.36 (2 H, m), 7.20 – 7.28 (2 H, m), 2.86 (3 H, d, J=4.58 Hz), 1.26 – 1.36 (4 H, m). LC-MS retention time: 1.92 min; m/z (MH+): 539. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna lOu CI 8 3.0x50mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220nM. The elution conditions employed a flow rate of 5 ml/min , a gradient of 100% solvent A / 0% solvent B to 0% solvent A / 100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% MeOH / 90% H20 / 0.1% trifluoroacetic acid and solvent B was 10% H20 / 90% MeOH / 0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode. Additional HPLC method: Solvent A = 5% CH3CN/95%H2O/0.1% TFA, Solvent B = 95% CH3CN/5% H2O/0.1% TFA, Start %B = 10, Final %B = 100, Gradient time = 15 min, Stop time = 18 min, Flow Rate = 1 ml/min. Column: Waters Sunfire C-18, 4.6 x 150 mm, 3.5 mm, Rt = 14.56 min, purity = 99%; Column: Waters Xbridge Phenyl column 4.6 x 150 mm, 3.5 mm, Rt = 13.20 min, purity = 97%.

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; BRISTOL-MYERS SQUIBB COMPANY; YEUNG, Kap-Sun; PARCELLA, Kyle, E.; BENDER, John, A.; BENO, Brett, R.; GRANT-YOUNG, Katharine, A.; HAN, Ying; HEWAWASAM, Piyasena; KADOW, John, F.; NICKEL, Andrew; WO2011/112191; (2011); A1;,
Chloride – Wikipedia,
Chlorides – 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. 18112-31-7, name is 3-Bromo-6-chloro-2-methylimidazo[1,2-b]pyridazine belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. category: chlorides-buliding-blocks

To a solution of 3-bromo-6-chloro-2-methylimidazo[1,2-b]pyridazine (865 mg, 5.16 mmol, 1.0 equiv) in acetonitrile (15 mL) was added boronic acid (5.16 mmol, 1.0 equiv), bis(triphenylphosphine)palladium(II)dichloride (0.516 mmol, 0.1 equiv), then sodium carbonate (1.0 M aqueous solution, 10 equiv). The reaction mixture was irradiated in the microwave at 150 C. for 10 min. Purification by column chromatography gave of the product.

The synthetic route of 18112-31-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Califia Bio, Inc.; GOODFELLOW, VAL S.; NGUYEN, THONG X.; RAVULA, SATHEESH B.; GELBARD, HARRIS A.; US2014/256733; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics