Tag: M.W=200-300

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. 1193-72-2 name is 1-Bromo-2,4-dichlorobenzene, 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. 1193-72-2

Part C. tert-butyl (7bR,11aS)-6-(2,4-dichloroanilino)-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate. An oven dried three-necked round bottom flask was fitted with septa, condenser, and a stopper. The flask was charged with tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate (134 mg, 0.36 mmol), 1-bromo-2,4-dichlorobenzene (70 mg, 0.31 mmol), NaOtBu (60 mg, 0.62 mmol), and anhydrous toluene (5 mL). The solution was purged with argon at 80 C. for 25 min then cooled to room temperature. While maintaining a blanket of argon, Pd2(dba)3 (3.4 mg, 3.7 mumol), and BINAP (7 mg, 11.2 mumol) were added quickly. The resulting mixture was heated to 80 C. for 20 hours under argon while monitoring the consumption of starting material by TLC (50% ethyl acetate/hexanes). After cooling to room temperature, the dark solution was diluted with ethyl ether (10 mL) and filtered through a pad of silica, washing with ether and ethyl acetate. The resulting solution was concentrated and chromatographed (Combiflash, 95:5 to 75:25 hexanes/ethyl acetate gradient) yielding the title compound (78 mg, 48%) as a tan solid. 1H NMR (CDCl3, 300 MHz) delta 1.41 (s, 9H), 1.79-1.97 (m, 2H), 2.85-3.18 (m, 6H), 3.46-3.61 (m, 4H), 3.68 (s, 2H), 5.84 (s, 1H), 6.71 (d, 1H, J=1.9 Hz), 6.79 (d, 1H, J=1.8 Hz), 6.89 (d, 1H, J=8.8 Hz), 7.01 (dd, 1H, J=2.3, 8.8 Hz), 7.29 (d, 1H, J=2.3 Hz) ppm.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Bromo-2,4-dichlorobenzene, and friends who are interested can also refer to it.

Reference:
Patent; Robichaud, Albert J.; Fevig, John M.; Mitchell, Ian S.; Lee, Taekyu; Chen, Wenting; Cacciola, Joseph; US2004/186094; (2004); A1;,
Chloride – Wikipedia,
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Some common heterocyclic compound, 823-57-4, name is 2-Bromo-5-chloroaniline, molecular formula is C6H5BrClN, 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. 823-57-4

The corresponding imidazopyridine (0.2 mmol) was added sequentially to a 25 ml Schlenk tube filled with oxygen and equipped with a magnetic stirrer at room temperature.Cuprous bromide (0.02 mmol), 2-bromo-5-chloroaniline (0.4 mmol),1,10-azaphenanthroline (0.04 mmol), pyridine (0.4 mmol),Carbon disulfide (0.4 mmol), NMP (2.0 mL), was added with a syringe under oxygen.The reaction tube was placed in a 130 C oil bath for 10 hours.The resulting solution was cooled to room temperature, and 2 mL of deionized water was added to the reaction solution.Mix well, each time with 3mL of ethyl acetate as extractant through liquid separation extraction operation,The crude product is extracted from the reaction solution, and the extract is combined.And removing the solvent by a rotary evaporator;The residue was purified on a silica gel column (silica gel size 200 mesh to 300 mesh,The eluent is petroleum ether/ethyl acetate (15:1 v/v),The target product was obtained in 69.1 mg, yield 82%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 823-57-4, its application will become more common.

Reference:
Patent; Qingdao University of Science and Technology; Yang Daoshan; Yan Qiuli; (17 pag.)CN110294757; (2019); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 1996-30-1, name is 3-Bromo-4-fluorochlorobenzene, This compound has unique chemical properties. The synthetic route is as follows., 1996-30-1

2-fluoro-5-chlorobromobenzene 18a (11.0g, 52.8mmol), ethynyltrimethyl Silane (7.7 g, 79 mmol) and triethylamine (60 mL) were mixed, and then cuprous iodide (100 mg, 0.53 mmol) and ditriphenylphosphine palladium chloride (1.86 g, 2.65 mmol) were added.The reaction mixture was heated to 80 C under a nitrogen atmosphere and stirring was continued for 4 hours.After the reaction was completed, the solution was desolvated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 100/1) to obtain the target product ((2-fluoro-5-chlorophenyl) ethynyl) trimethyl. Silane 18b (11.0 g, yellow oil), yield: 90%.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; BEIJING TIANCHENG PHARMA CO., LTD.; CHEN, XIANGYANG; GAO, YINGXIANG; KONG, NORMAN XIANGLONG; (118 pag.)TW2019/38538; (2019); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

The chemical industry reduces the impact on the environment during synthesis 823-57-4, name is 2-Bromo-5-chloroaniline, I believe this compound will play a more active role in future production and life. 823-57-4

Compound 37b (4.2 g, 20.3 mmol) is melted at 500C in a 100 mL round-bottomed flask containing a stirring bar and immersed in an oil bath. A solution of zinc chloride (700 mg, 5.03 mmol) and ferric chloride (540 mg, 3.25 mmol) in 3.3 mL of water is added in one portion followed by 20 m L of absolute EtOH. The flask is stoppered with a rubber septa and a needle is inserted to avoid any pressure build-up. The mixture is warmed to 800C and acrolein (1.68 mL, 24.4 mmol) is added via a syringe pump over a 2 h period. After the addition, the mixture is stirred at 800C for 1 h and an additional amount of solid ferric chloride is added (4.1 g, 25.3 mmol). The mixture is stirred at 8O0C for about an extra 24 h and then concentrated under vacuum to give a semi-solid residue. 200 mL of water is added followed by a 10 N aqueous solution of NaOH (20 mL) and 200 mL of CH2CI2. After shaking the mixture for a few minutes, the solid is filtered over a pad of Celite.(R). and the filtrate is transferred into a separatory funnel. The organic layer is separated and the aqueous layer is extracted with CH2CI2. The combined organic extracts are washed with brine, dried (Na2SO4), filtered and concentrated under vacuum to give 3.69 g of a brown solid. This solid is triturated in hot CH3CN and filtered. The solid is discarded and the filtrate is concentrated under vacuum to give 2.3 g of a brown semi-solid. This material is purified on a CombiFlash.(R). Companion apparatus on 40 g silica gel column eluted with EtOAc/hexanes gradient. After evaporation of the solvent 13-152under vacuum, the desired compound 37c is isolated as a yellow solid (390 mg, 8percent yield).

The chemical industry reduces the impact on the environment during synthesis 823-57-4. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GmbH; WO2009/62308; (2009); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

19393-92-1, A common heterocyclic compound, 19393-92-1, name is 2-Bromo-1,3-dichlorobenzene, molecular formula is C6H3BrCl2, 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 148 (7bR,11aS)-N-(2,6-dichlorophenyl)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indol-6-amine An oven-dried three-necked round bottom flask was fitted with a septa, condenser, and a stopper. The flask was charged with tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate from EXAMPLE 33, Part B (107 mg, 0.297 mmol), 2,6-dichlorobromobenzene (56 mg, 0.25 mmol), NaOt-Bu (71 mg, 0.74 mmol), and anhydrous toluene (6 mL). The solution was purged with argon at 80¡ã C. for 25 min then cooled to room temperature. While maintaining a blanket of argon, Pd2(dba)3 (5 mg, 6 mumol), and BINAP (7 mg, 12 mumol) were added quickly. The resulting mixture was heated to 80¡ã C. for 20 h under argon. After cooling to room temperature, the dark solution was diluted with ethyl ether (10 mL) and filtered through a pad of silica, washing with ether. The resulting solution was concentrated and the residue was chromatographed (10-12percent ethyl acetate in hexanes gradient) yielding an N-BOC intermediate (90 mg, 72percent) as a yellow foam: 1H NMR (300 MHz, CDCl3) delta 1.40 (s, 9H), 1.71-1.92 (m, 2H), 2.79-3.13 (m, 3H), 3.15-3.96 (m, 9H), 5.71 (s, 1H), 6.29-6.50 (m, 2H), 6.91-7.00 (s, 1H), 7.32 (d, 2H, J=8 Hz). This intermediate (90 mg, 0.18 mmol) was dissolved in dichloromethane (8 mL) and chilled in an ice bath. Trifluoroacetic acid (2 mL) was then added and the solution was stirred at room temperature for 2 h. The solution was made basic with 3 N NaOH, and extracted with dichloromethane. The organic layers were combined, dried over NaSO4 and concentrated to a yellow oil. An off-white solid was obtained upon trituration with ethyl acetate/hexanes yielding 58 mg (81percent) of the title compound of EXAMPLE 148. 1H NMR (300 MHz, CDCl3) delta 1.72-1.85 (m, 2H), 2.51-2.65 (m, 1H), 2.76-3.09 (m, 6H), 3.10-3.21 (m, 1H), 3.36-3.42 (m, 1H), 3.47-3.79 (m, 4H), 5.71 (s, 1H), 6.34 (s, 1H), 6.42 (s, 1H), 6.95 (t, 1H, J=8 Hz), 7.32 (d, 2H, J=8 Hz). LRMS (ES)+: 406 (M+H)+.

The synthetic route of 19393-92-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Robichaud, Albert; Fevig, John M.; Mitchell, Ian S.; Lee, Taekyu; Chen, Wenting; Cacciola, Joseph; US2002/173503; (2002); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

96558-78-0, These common heterocyclic compound, 96558-78-0, name is 3-Bromo-5-chlorophenylamine, 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.

3-chloro-5-bromoaniline (1 g, 4.84 mmol) was dissolv ed in 75% I LSO ( 10 mL). Then glycerol (1.1 1 g, 12.1 mmol ) and nitrobenzene (0.59 g. 4.84 mmol ) were added. The reaction mixture was stirred at 150C for 3 hours under N2. EtOAc (50 ml ) was added and the mixture was adjusted to pH to 6-7 with a 30% solution of NaOH in water. The solid was filtered off over celite and the organic layer was separated and ev aporated. The residue was purified by flash column chromatograph over silica gel (gradient eiuent: petroleum ether EtOAc from 20/ 1 to 5/1). The desired fractions were collected and the solvent was evaporated to give a mixture of intermediate 457 and intermediate 458 (750 mg) as a white solid.

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 96558-78-0.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; WU, Tongfei; BREHMER, Dirk; BEKE, Lijs; BOECKX, An; DIELS, Gaston, Stanislas, Marcella; GILISSEN, Ronaldus, Arnodus, Hendrika, Joseph; LAWSON, Edward, Charles; PANDE, Vineet; PARADE, Marcus, Cornelis, Bernardus, Catharina; SCHEPENS, Wim, Bert, Griet; THURING, Johannes, Wilhelmus, John, F; VIELLEVOYE, Marcel; SUN, Weimei; MEERPOEL, Lieven; (375 pag.)WO2017/32840; (2017); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

1996-29-8, Adding a certain compound to certain chemical reactions, such as: 1996-29-8, name is 1-Bromo-4-chloro-2-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 1996-29-8.

A 2 L round bottom flask was charged with 1-bromo-4-chloro-2-fluorobenzene(1-bromo-4-chloro-2-fluorobenzene, 50 g, 238.7 mmol)And anhydrous tetrahydrofuran 900 ml was added and the mixture was cooled to -78C with stirring.N-butyl lithium (2.5 M hexane solution; 100 ml, 250 mmol)And the mixture was stirred for 1 hour.Trimethylborate (31.9 ml, 286 mmol) was slowly added thereto,After 30 minutes, 600 ml of a 1N hydrogen chloride aqueous solution was addedThe temperature was raised to room temperature while stirring.The organic layer was separated, dried over anhydrous magnesium sulfate, and filtered. The mixture was distilled under reduced pressure, concentrated, and extracted with chloroform and hexaneAnd recrystallized to obtain Compound 1 (33.7 g, 193.3 mmol) in a yield of 81%.

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-Bromo-4-chloro-2-fluorobenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; LG Chemical Co., Ltd.; Hong, Sung Gil; Kim, Yeon Hwan; Kim, Sung So; Ho, Jung Oh; Cho, Sung Mi; Kim, Hyung Suk; (37 pag.)KR101680413; (2016); B1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

823-57-4, 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 823-57-4 as follows.

A 10 L round-bottom flask was charged with 200 g (1.64 mol, 1.05 eq.) of Phenylboronic acid, 322 g (1.56 mol, 1 eq.) of 2-bromo-5-chloroaniline, 90 g (78.10 mmol, 0.05 eq.) of Pd(PPh3)4, and 646 g (4.69 mol, 3 eq.) of K2CO3, after which toluene/EtOH/H2O was added thereto, and the mixture was stirred under reflux. After completion of the reaction, the mixture was extracted with MC/H2O and the MC layer was dried over MgSO4. Purification was performed using a silica-gel column to obtain 254 g of Core 1-1 at a yield of 80percent.

According to the analysis of related databases, 2-Bromo-5-chloroaniline, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SOULBRAIN CO., LTD.; HA, Jong Jin; YOO, Hyun Young; KIM, Sung Soo; LEE, Seok Jong; (103 pag.)US2019/161485; (2019); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

96558-78-0,Some common heterocyclic compound, 96558-78-0, name is 3-Bromo-5-chlorophenylamine, molecular formula is C6H5BrClN, 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.

(S)-tert-Butyl l-(3-bromo-5-chlorophenylamino)-l-oxo-3-phenylpropan-2-ylcarbamate (46.D). 3-bromo-5-chlorobenzenamine (3.73 g, 18 mmol) and (S)-2-(tert- butoxycarbonyl)-3-phenylpropanoic acid (4.8g, 18 mmol) were dissolved in DMF (100 mL, 1291 mmol) then triethylmine (5 mL, 36 mmol) and HBTU (14 g, 36 mmol) were added and the mixture was stirred for 14 h. After 14 hours the reaction was diluted with 500 mL EtOAc and the organic was washed with IN HCl and saturated bicarbonate solution. The extract was concentrated under reduced pressure on a rotary evaporator to afford a residue. The residue was purified on silica eluting with EtO Ac/Hex in a linear gradient.

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

Reference:
Patent; AMGEN INC.; DU, Xiaohui; FU, Zice; HOUZE, Jonathan, B.; JIAO, Xianyun; KIM, Yong-jae; LI, Leping; LIU, Jinqian; LIZARZABURU, Mike; MEDINA, Julio; SHEN, Wang; TURCOTTE, Simon; YU, Ming; WO2010/93849; (2010); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

13526-66-4, Adding some certain compound to certain chemical reactions, such as: 13526-66-4, name is 3-Bromo-6-chloroimidazo[1,2-b]pyridazine, 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 13526-66-4.

13.9 g (59.8 mmol) 3-bromo-6-chloro-imidazo[1 ,2-b]pyridazine were suspended in 508 mL 1 ,4-dioxane. 10.1 g (62.8 mmol) 2-benzofuranylboronic acid, 2.76 g (2.29 mmol) tetrakis(triphenylphosphino)palladium-(0) and 19.0 g (179 mmol) sodium carbonate were added. The obtained mixture was heated to 100C for 24 h. 400 mL of a saturated aqueous ammonium chloride solution were added. The obtained mixture was extracted with ethyl acetate. The combined organic layers were washed with brine and dried over magnesium sulfate. After evaporation of the solvent, the obtained solid material was digested in 40 mL of a mixture of dichloromethane and methanol (8:2), filtered off and dried in vacuo to yield 5.42 g (44%) of the title compound as solid material. 1H-NMR (300 MHz, DMSO-d6): delta [ppm]= 7.23 – 7.40 (m, 2H), 7.51 (d, 1 H), 7.59 – 7.67 (m, 2H), 7.77 (d, 1 H), 8.33 – 8.40 (m, 2H). LCMS (Method 1 ): Rt = 1 .35 min; MS (ESIpos) m/z = 270 [M+H]+.

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 13526-66-4.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; ZORN, Ludwig; EIS, Knut; SCHULZE, Volker; SUeLZLE, Detlev; PUeHLER, Florian; LIENAU, Philip; BOeMER, Ulf; PETERSEN, Kirstin; HAeGEBARTH, Andrea; WO2014/118135; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics