Tag: M.W=200-300

Some common heterocyclic compound, 3335-98-6, name is 1-Phenyloxindole, molecular formula is C14H11NO, 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. 3335-98-6

General procedure: To a precooled stirring suspension of NaH (6.0 mmol, 0.144 g) in THF (10 mL) at -78 C was added a solution of N-methyloxindole (5a) (6.0 mmol, 0.883 g) in THF (10 mL) dropwise. Then the cooling bath was removed and stirring continued for 5 min (till the formation of clear solution). Then the reaction mixture was again cooled to -78 C and a solution of methyl 3-hydroxy-2-methylene-3-phenylpropanoate (6a) (2.0 mmol, 0.468 g) in THF (15 mL) was added dropwise over 30 min. After stirring for further 10 min at the same temperature, the cooling bath was removed and the reaction was quenched with saturated NH4Cl solution and extracted with EtOAc (3¡Á30 mL). Combined organic layer was dried over anhydrous Na2SO4.. Solvent was removed and the crude obtained was purified by column chromatography(10-15% EtOAc in hexanes) provided title compound (7a) (0.539 g) as a colorless solid in 84% yield.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3335-98-6, its application will become more common.

Reference:
Article; Basavaiah, Deevi; Lingam, Harathi; Babu, Thelagathoti Hari; Tetrahedron; vol. 74; 19; (2018); p. 2306 – 2313;,
Indoline – Wikipedia,
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Some common heterocyclic compound, 675109-26-9, name is 6-Bromoisoindolin-1-one, molecular formula is C8H6BrNO, 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. 675109-26-9

(6-( 1 – (and 2-)(4-methoxybenzyl)-2H-tetrazol-5 -yl)-4′-methyl-5-sulfamoyl- [ 1 , 1 ‘- biphenyl]-3-yl)boronic acid (40 mg, 0.083 mmol) and 6-bromoisoindolin-l-one (19.47 mg, 0.092 mmol) was suspended in ethanol (835 mu) and potassium phosphate tribasic (250 mu, 0.250 mmol). The reaction mixture was sparged with 2 for 5 min. 1 , l’-bis(di-tert- butylphosphino)ferrocene palladium dichloride (5.44 mg, 8.35 muiotaetaomicron) was added and the reaction mixture micro waved at 1 10C for 90 min. The crude reaction mixture was diluted with EtOAc and water. The aqueous phase was extract with EtOAc (x2), then the combined extracts were washed with brine, dried over Na2S04, filtered, and concentrated. The reaction mixture was purified by reverse phase HPLC on a Cis column and then eluted with 10% to 100% MeCN in water. The major UV active material was lyopholized to provide a white solid that was utilized directly in the deprotection. LC-MS: calculated for C3oH26N604S 566.2; observed m/e: 467.5 (M+H)+. The resulting solid was dissolved in TFA and heated to 45C overnight, then concentrated. The residue was purified by reverse phase HPLC on a Cis column eluted with 0% to 80% MeCN in water. The major UV active material was lyopholized to provide 4′-methyl-5- (l-oxoisoindolin-5-yl)-2-(2H-tetrazol-5-yl)-[l, l’-biphenyl]-3-sulfonamide. LC-MS: calculated for C22H18N603S 446.1 ; observed m/e: 447.4 (M+H)+; 1H NMR delta (ppm) (DMSO): 8.72 (s, 1H), 8.44 (s, 1H), 8.16 (s, 1H), 8.12 (d, 1H), 8.05 (s, 1H), 7.77 (d, 1H), 7.60 (s, 2H), 7.11-7.05 (m, 4H), 4.48 (s, 2H), 2.27 (s, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 675109-26-9, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MANDAL, Mihir; TANG, Haifeng; XIAO, Li; SU, Jing; LI, Guoqing; YANG, Shu-Wei; PAN, Weidong; TANG, Haiqun; DEJESUS, Reynalda; HICKS, Jacqueline; LOMBARDO, Matthew; CHU, Hong; HAGMANN, William; PASTERNAK, Alex; GU, Xin; JIANG, Jinlong; DONG, Shuzhi; DING, Fa-Xiang; LONDON, Clare; BISWAS, Dipshikha; YOUNG, Katherine; HUNTER, David, N.; ZHAO, Zhiqiang; YANG, Dexi; WO2015/112441; (2015); A1;,
Indoline – Wikipedia,
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A common compound: 883-44-3, name is 2-(3-Hydroxypropyl)isoindoline-1,3-dione, belongs to indolines-derivatives compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below. 883-44-3

The reaction was carried out with oven dried glassware. DMSO (85 mul, 1.1 mmol) was added to oxalyl chloride solution (0.35 mL 2 M DCM solution with 5 mL dry DCM) at -78 C. The reaction mixture was stirred at -78 C. for 10 min. 2-(3-Hydroxy-propyl)-isoindole-1,3-dione solution (102 mg, 0.5 mmol, in 2 mL DCM) was added drop wise in 2 min. Then triethylamine (0.35 mL, 2.5 mmol) was added drop wise in 2 min. The mixture was stirred for additional 30 minutes at -78 C. and was warmed up to room temperature. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate, dried over MgSO4, filtered, and the filtrated was concentrated in vacuo. The crude product was purified by flash chromatography to give 3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionaldehyde.

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, 883-44-3, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Boyce, Rustum S.; Guo, Hongyan; Mendenhall, Kris G.; Walter, Annette O.; Wang, Weibo; Xia, Yia; US2006/84687; (2006); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

A common heterocyclic compound, 4702-13-0, name is N-Phthaloylglycine, molecular formula is C10H7NO4, 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. 4702-13-0.

Commercially available N-phthaloylglycine (32, 200mg, 0.975mmol) was dissolved in SOCl2 (2.84mL) and refluxed for 2h. After evaporation of the solvent under reduced pressure, the obtained white solid was solubilized in THF (1.7mL), and treated with tris(trimethylsilyl)phosphite (978muL, 2.92mmol) at 0C for 15min, and then stirred at room temperature for 15min. Methanol (4mL) was added and the solution was stirred for 1hat room temperature. The solvent was evaporated under vacuum and the white solid was washed three times with a toluene/hexane mixture (1:1) (4mL), washed with Et2O and dried under vacuum, obtaining the intermediate 37. Yield: 337mg (98.5%).

The synthetic route of N-Phthaloylglycine has been constantly updated, and we look forward to future research findings.

Reference:
Article; Savino, Salvatore; Toscano, Annamaria; Purgatorio, Rosa; Profilo, Emanuela; Laghezza, Antonio; Tortorella, Paolo; Angelelli, Mariacristina; Cellamarea, Saverio; Scala, Rosa; Tricarico, Domenico; Thomas Marobbio, Carlo Marya; Perna, Filippo; Vitale, Paola; Agamennone, Mariangela; Dimiccoli, Vincenzo; Tolomeo, Anna; Scilimati, Antonio; European Journal of Medicinal Chemistry; vol. 158; (2018); p. 184 – 200;,
Indoline – Wikipedia,
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104618-32-8,Some common heterocyclic compound, 104618-32-8, name is 2-(4-Oxocyclohexyl)isoindoline-1,3-dione, molecular formula is C14H13NO3, 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 4 3-Amino-6-bromo-1,2,3,4-tetrahydrocarbazole hydrochloride Reaction of 4-bromophenylhydrazine hydrochloride (4.0g, 18.1 mmol) with 4-phthalimido-cyclohexanone (4.39g, 18.1 mmol) in refluxing n-butanol for 20 min, followed by cooling, filtration, and evaporation of the filtrate to dryness yielded 3-phthalimido-6-bromo-1,2,3,4-tetrahydrocarbazole as an orange solid (7.45g).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(4-Oxocyclohexyl)isoindoline-1,3-dione, its application will become more common.

Reference:
Patent; SMITHKLINE BEECHAM PLC; EP603432; (1994); A1;; ; Patent; Smithkline Beecham plc; US5827871; (1998); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

3335-98-6, 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 3335-98-6 as follows.

PREPARATION M7 1-Phenyl-3-(hydroxymethylene)-2(1H,2H)-indolone Potassium t-butoxide (1.63 g, 14.5 mmoles) and 5 ml absolute ethanol were heated to 80. 1-Phenyl-2(1H,3H)-indolone (2.09 g, 10 mmoles) was added, followed by ethyl formate (1.09 ml, 13.5 mmoles). The mixture was heated 5 minutes, cooled to 25, and the nearly solid mass diluted with 50 ml H2 O and crushed ice, acidified to pH 3 with 3N HCl and title product recovered by filtration, 2.2 g, m.p. 192-195; m/e 237. cf J. Prakt. Chem. 135:345-360 (1932); J. Med. Chem. 8:637 (1965).

According to the analysis of related databases, 3335-98-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Pfizer Inc.; US4476307; (1984); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

3416-57-7, Adding some certain compound to certain chemical reactions, such as: 3416-57-7, name is 2-(2-Oxopropyl)isoindoline-1,3-dione, 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 3416-57-7.

5.5. Examples 5-13; Similar to Examples 3 and 4,5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-ol was prepared using the following solvent/base combinations for the preparation of the 2-amino-4-methyl-1H-pyrrole-3-carboxamide intermediate:

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 3416-57-7.

Reference:
Patent; Bednarz, Mark S.; Kanamarlapudi, Ramanaiah C.; Wu, Wenxue; US2008/97098; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 15362-40-0 name is 1-(2,6-Dichlorophenyl)-2-indolinone, 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. 15362-40-0

Pyrrole-2-carboxaldehyde (1 mmol) and 4-fluorobenzyl bromide (1.5 mmol) were reacted in the presence of NaH (1.5 mmol) in DMF (solvent) at 0 – 25 C for 30 min. The progress of the reaction was monitored with TLC. After completion, the reaction was quenched by the addition of water and the crude product was isolated by extraction with ethyl acetate (2 x 50 ml). The organic layers were combined, dried over Na2SO4 and distilled in vacuum to give N-(4-flurobenzyl)pyrrole-2-carboxaldehyde (A) which was purified by column chromatography using ethyl acetate: hexane (1:50). A (1 mmol) was reacted with 1-(2,6-dichlorophenyl)-2-indolinone (1.2 mmol) in the presence of piperidine (0.2 mmol) in CHCl3/ DMF under microwave irradiations at 100 C for 1h. The progress of the reaction was monitored with TLC, after completion reaction was worked up by adding water and extraction with chloroform (2 x 50 ml). Combined organic layers were dried over Na2SO4 and distilled in vacuum to give crude product 3b which was purified by column chromatography using ethyl acetate: hexane (3:50) as eluent. Yellow Solid, yield 75 %, mp 130-132 C; IR (KBr): 3077, 2929, 1702, 1600, 1509, 1396; 1H NMR (500 MHz, CDCl3) delta: 1H NMR (500 MHz, CDCl3, 25 C, TMS) delta: 5.38 (s, 2H, CH2), 6.41-6.43 (m, 2H, ArH), 7.05-7.10 (m, 4H, ArH), 7.13-7.16 (m, 3H, ArH), 7.31 (d, 1H, J = 7.55 Hz, ArH), 7.38 (t, 1H, J = 7.95 Hz, ArH), 7.42 (s, 1H, =CH), 7.53 (d, 2H, J = 8.08 Hz, ArH), 8.48 (dd, 1H, J = 3.45 Hz, 1.29 Hz, ArH); 13C NMR (125 MHz, CDCl3, normal/DEPT-135) delta: 50.6 (-ve, CH2), 108.7 (+ve, CH), 110.9, (+ve, CH), 116.0 (+ve, CH), 116.1 (+ve, CH), 117.3 (+ve, CH), 117.7 (+ve, CH), 122.0 (+ve, CH), 122.2 (+ve, CH), 122.6 (+ve, CH), 125.1 (ArC), 127.3 (+ve, CH), 127.9 (+ve, CH), 128.0 (+ve, CH), 128.5 (ArC), 128.8 (+ve, CH), 129.0 (+ve, CH), 130.4 (+ve, CH), 131.1 (ArC), 133.1 (ArC), 135.9 (ArC), 139.3 (ArC), 161.3-161.4 (J = 247 Hz, CF), 164.8 (C=O); HRMS (ESI) m/z for C26H17Cl2FN2O [M+H]+ calcd. 463.0774, found 463.0734.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-(2,6-Dichlorophenyl)-2-indolinone, and friends who are interested can also refer to it.

Reference:
Article; Kaur, Jagroop; Kaur, Baljit; Singh, Palwinder; Bioorganic and Medicinal Chemistry Letters; vol. 28; 2; (2018); p. 129 – 133;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

The chemical industry reduces the impact on the environment during synthesis 2436-29-5, name is 3-(1,3-Dioxoisoindolin-2-yl)propanal, I believe this compound will play a more active role in future production and life. 2436-29-5

Example 27: 2-Fluoro-lambda/-[4-(5-{[3-(4-fluoro-1 -piperidinyl)propyl]amino}-1 ,3,4- oxadiazol-2-yl)phenyl]benzamide; 4-Fluoropiperidine hydrochloride (164 mg, 1.18 mmol) was partitioned between dichloromethane (5 mL) and aqueous sodium hydroxide (2M, 5 mL) and the aqueous phase extracted with further dichloromethane (5 mL). The organic phases were combined and isolated (phase separator). To this solution was added 3-(1 ,3-dioxo-1 ,3-dihydro-2H- isoindol-2-yl)propanal (300 mg, 1.48 mmol) and sodium triacetoxyborohydride (470 mg, 2.22 mmol) and then the reaction was stirred at room temperature overnight. Methanol was added to the reaction mixture which was applied to an SCX cartridge (10 g), washed with methanol and eluted with 2M ammonia in methanol. The solvent was removed in vacuo and the residue was taken up in a solution of methylamine in ethanol (33 %, 2 mL) and the reaction stirred at room temperature overnight. Diethyl ether (7 mL) was then added and the resultant solid removed by filtration. The solvent was removed in vacuo and the crude amine, [3-(4-fluoro-1-piperidinyl)propyl]amine, then taken up in dioxane (3 ml.) and 2-fluoro-lambda/-(4-{5-[(phenylmethyl)sulfonyl]-1 ,3,4-oxadiazol-2-yl}phenyl)benzamide (70 mg, 0.16 mmol) was added. The reaction was heated in the microwave at 100 0C for 15 minutes. The solvent was removed in vacuo and the residue purified by mass directed auto-preparative liquid chromatography. The product was applied to an SCX cartridge, washed with methanol and eluted with 2M ammonia in methanol. The solvent was removed in vacuo to furnish the title product (45 mg) as a white solid. LCMS (ES+ve): [IvHH]+ at m/z 442 (C23H25F2N5O2 requires [M+H]+ at m/z 442.

The chemical industry reduces the impact on the environment during synthesis 2436-29-5. I believe this compound will play a more active role in future production and life.

Reference:
Patent; GLAXO GROUP LIMITED; WO2007/138033; (2007); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding some certain compound to certain chemical reactions, such as: 2058-72-2, name is 5-Bromo-1-methylindoline-2,3-dione, 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 2058-72-2. 2058-72-2

General procedure: A mixture of isatin (1a) (0.3 gm, 2.0 mmol) and enaminone (2a) (0.333 gm,2.4 mmol) in 10 mL of water was heated in an oil bath at 80C for 9 hours. Initially,orange-colored reaction mixture appeared to be homogeneous but with the progress ofthe reaction, yellow color solid precipitated out. After the TLC indicated the completeconsumption of starting materials, the precipitated solid was filtered off. The solid wasthen dried under vacuum and purified by silica gel column chromatography by using EA: hexane (8:2) as an eluent to provide the desired product.

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 5-Bromo-1-methylindoline-2,3-dione.

Reference:
Article; Tiwari, Keshri Nath; Thakar, Snehal Rajendra; Kumar, Vaneet; Prabhakaran; Synthetic Communications; vol. 48; 23; (2018); p. 2965 – 2972;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem