Author: tianli

480-91-1,Some common heterocyclic compound, 480-91-1, name is Isoindolin-1-one, molecular formula is C8H7NO, 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.

A mixture of 84B (225 mg, 1.0 mmol), 197 isoindolin-1-one (133.1 mg, 1.0 mmol), 51 Pd2(dba)3 (28 mg, 0.03 mmol), Xantphos (29 mg, 0.05 mmol) and 50 Cs2CO3 (391 mg, 1.2 mmol) in 52 dioxane (45 mL) was heated to 100 C. overnight. After cooling to room temperature, the reaction mixture was filtered. The filtrate was concentrated under vacuum and the residue was purified by column chromatography on silica gel (1%-30% 32 EtOAc in 60 pet. ether) to provide 233 compound 84 (170 mg, 61% yield) as a white solid: 1H NMR (400 MHz, CDCl3) delta 8.72 (dd, J=7.6 Hz, 6.4 Hz, 1H), 8.57 (d, J=1.2 Hz, 1H), 8.01-7.94 (m, 3H), 7.86 (d, J=0.8 Hz, 1H), 7.69-7.65 (m, 1H), 7.59-7.52 (m, 2H), 5.14 (s, 2H) ; ESI m/z 278.0 [M+H]+ .

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Isoindolin-1-one, its application will become more common.

Reference:
Patent; Seal Rock Therapeutics, Inc.; BROWN, Samuel David; US2018/291002; (2018); A1;,
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

20876-36-2, Adding a certain compound to certain chemical reactions, such as: 20876-36-2, name is 5-Aminoindolin-2-one, belongs to indolines-derivatives 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 20876-36-2.

5-(4-Methoxycarbonylbenzamido)-2-oxindole A mixture of 82.0 mg 5-amino-2-oxindole and 131.0 mg 4-methoxycarbonylbenzoyl chloride in pyridine was stirred at room temperature for 3 hr and poured into ice water. The precipitate was filtered, washed with water and dried in a vacuum oven to give 138.0 mg of 5-(4-methoxycarbonylbenzamido)-2-oxindole (81percent yield).

According to the analysis of related databases, 20876-36-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SUGEN, Inc.; US2003/69421; (2003); A1;; ; Patent; Sugen, Inc.; US6051593; (2000); A;,
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

Some common heterocyclic compound, 59-48-3, name is Indolin-2-one, molecular formula is C8H7NO, 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. 59-48-3

2. 5-Amino-3-(3,5-diethyl-1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one 2-Oxindole (6.5 g) was dissolved in 25 mL of concentrated sulfuric acid and the mixture maintained at -10-15 C. while 2.1 mL of fuming nitric acid was added dropwise. After the addition of the nitric acid, the reaction mixture was stirred at 0 C. for 0.5 hr and poured into ice-water. The precipitate was collected by filtration, washed with water and crystallized from 50% acetic acid. The final crystalline product was then filtered, washed with water and dried under vacuum to give 6.3 g (70%) of 5-nitro-1,3-dihydro-indol-2-one.

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

Reference:
Patent; Sugen, Inc.; US6846839; (2005); B1;,
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

324-03-8,Some common heterocyclic compound, 324-03-8, name is 6-Fluoroindoline-2,3-dione, molecular formula is C8H4FNO2, 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.

In a RB flask charge under stirring at 2530 C, 336 gr of crude compound of formula lila (0,0203 mole) and dissolve in 336 mL tetrahydrofuran. To the clear solution add 1.902 gr cyanoacetic acid (0.0224 mole) and 2.7 mL triethylamine (0.0194 mole). Warm up reaction mass to reflux and continue stirring overnight.When reaction is completed, allow reaction mass to cool down (2530 C). Concentrate solvent till total dryness. To the oily residue add 168 mL D.M. water and extract three times with 336 mL ethyl acetate (each time). Combine organic layers, dry over sodium sulfate, filter and evaporate solvent till total dryness, to provide 4.116 gr of crude compound of formula ha,IH NMR (300 MHz, DMSOd6) 7,47 (dd, J1 = 82 Hz, J2 = 56 Hz, 1H), 689 682(m, 1H), 67 (dd, Ji = 9,2 Hz, J2 = 24 Hz, 1H), 664 (s, 1H), 336 (s, IH), 309 294(m, 2H). 13C NMR (75 MHz, DMSOd6) 177,4, 1636, 1439, 1438, 126,2, 1 17A, 1085, 987, 720, 26,4.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 324-03-8, its application will become more common.

Reference:
Patent; PHARMATHEN S.A.; KOFTIS, V. Theocharis; NEOKOSMIDIS, Efstratios; RAPTIS, Christos; TRAKOSSAS, Sakellarios; ANDREOU, Thanos; VARVOGLI, Anastasia – Aikaterini; (30 pag.)WO2017/67670; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

The chemical industry reduces the impact on the environment during synthesis 15362-40-0, name is 1-(2,6-Dichlorophenyl)-2-indolinone, I believe this compound will play a more active role in future production and life. 15362-40-0

Pyrrole-2-carboxaldehyde (1 mmol) and 4-chlorobenzyl chloride (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 the completion, reaction was quenched by adding water and worked up 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-chlorobenzyl)pyrrole-2-carboxaldehyde (A) which was further 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, the 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 3c which was purified by column chromatography using ethyl acetate: hexane (3:50) as eluent. Yellow Solid, yield 70 %, mp 122-124 C; IR (KBr): 3054, 2928, 1698, 1600, 1485, 1367; 1H NMR (500 MHz, CDCl3) delta: 1H NMR (500 MHz, CDCl3, 25 C, TMS ) delta: 5.29 (s, 2H, CH2), 6.44-6.46 (m, 2H, ArH), 6.97-6.98 (m, 1H, ArH), 7.08-7.10 (m, 3H, ArH), 7.21 (t, 1H, J = 6.74 Hz, ArH), 7.31 (d, 2H, J = 8.48 Hz, ArH), 7.37-7.41 (m, 2H, ArH), 7.53 (d, 2H, J = 8.52 Hz, ArH), 7.71 (s, 1H, =CH), 8.25 (d, 1H, J = 7.4 Hz, ArH), 8.23 (dd, 1H, J = 4.37 Hz, 1.29 Hz, ArH) ; 13C NMR (125 MHz, CDCl3, normal/DEPT-135) delta: 50.4 (-ve, CH2), 109.0 (+ve, CH), 110.5 (+ve, CH), 116.5 (+ve CH), 117.4 (ArC), 117.8 (+ve, CH), 121.9 (ArC), 122.0 (+ve, CH), 122.4 (+ve, CH), 122.5 (+ve, CH), 124.8 (+ve CH), 127.1 (+ve, CH), 127.5 (+ve, CH), 128.1 (+ve, CH), 128.9 (ArC), 129.1 (+ve, CH), 129.3 (+ve, CH), 130.5 (+ve, CH), 133.8 (ArC), 135.5 (ArC), 135.8 (ArC), 141.3 (ArC), 164.8 (CF), 167.8 (C=O); HRMS (ESI) m/z for C26H17Cl3N2O [M+H]+ calcd. 479.0479, found 479.0421.

The chemical industry reduces the impact on the environment during synthesis 15362-40-0. I believe this compound will play a more active role in future production and life.

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