Author: tianli

Some common heterocyclic compound, 774-47-0, name is 5,6-Difluoroindoline-2,3-dione, molecular formula is C8H3F2NO2, 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. 774-47-0

Weigh rapamycin (0.05mmol), isatin 3n (0.10mmol) and rhodium octanoate (0.0005mmo),They were placed in a reaction flask, 2.0 mL of dry dichloromethane was added, and after stirring at room temperature for 5 minutes,Phenyldiazo 2a (0.10 mmol) was weighed and dissolved in dry dichloromethane (1.0 mL), and slowly added dropwise to the reaction system (about 1 hour), and stirring was continued for half an hour.The solvent was removed by rotary evaporation to give a crude product. The rapamycin analog I-n was obtained by column chromatography (eluent: petroleum ether: ethyl acetate = 1:10 to 1:4).The yield was 90%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 774-47-0, its application will become more common.

Reference:
Patent; Ha Yao Cihang Pharmaceutical Co., Ltd.; Changsha Tianci Bio-pharmaceutical Technology Co., Ltd.; Changsha Cihang Pharmaceutical Institute Co., Ltd.; Duan Yanwen; Huang Yong; Qiu Lin; Wen Zhongqing; Su Meng; (38 pag.)CN109776571; (2019); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 1074-82-4, name is Potassium 1,3-dioxoisoindolin-2-ide, 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. 1074-82-4

To a solution of phtalamide potassium salt (6 g, 32.4 mmol) in DMF (40 mL), was added allyl bromide (2.78 mL, 32.4 mmol). The solution was heated to 7O0C and stirred for 16h. The DMF was removed by rotary evaporation and aqueous extraction was performed with ethyl acetate and water and the organic layer was separated, dried with NaSO4 and concentrated. The residue was purified by silica gel column chromatography with a gradient of ethyl acetate (20-80percent) in hexanes to afford 241 (3.4 g, 57percent) as a white solid.(DMSO-croe) delta(ppm): 7.89 – 7.80 (m, 4H)1 5.90 – 5.80 (m, 1H), 5.12 (t, J=1.6 Hz, 1H), 5.10 -5.06 (m, 1 H), 4.16 (dt, J=5.1 , 1.8 Hz, 2H)

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 1074-82-4.

Reference:
Patent; METHYLGENE INC.; WO2006/102760; (2006); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

1074-82-4,Some common heterocyclic compound, 1074-82-4, name is Potassium 1,3-dioxoisoindolin-2-ide, molecular formula is C8H4KNO2, 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 a solution of l-(bromomethyl)-4-methylbenzene (5 g, 27 mmol) in DMF (30 mL) was added potassium l,3-dioxoisoindolin-2-ide (7.51 g, 40.5 mmol) .The mixture was stirred at 100C for 14 hours. The reaction mixture was concentrated under reduced pressure to remove DMF. The residue was purified by column chromatography (S1O2, petroleum ethenethyl acetate = 0 to 20%) to give 2- (4-methylbenzyl)isoindoline-l,3-dione (5.50 g, 81% yield). XH NMR (chloroform-d 400 MHz) d 7.85 (d, J = 3.2 Hz, 2H), 7.84 (d, J = 3.2 Hz, 2H), 7.34 (d, J = 7.6 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 4.82 (s, 2H), 2.32 (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 Potassium 1,3-dioxoisoindolin-2-ide, its application will become more common.

Reference:
Patent; H. LUNDBECK A/S; KEHLER, Jan; JUHL, Karsten; MARIGO, Mauro; VITAL, Paulo, Jorge, Vieira; JESSING, Mikkel; LANGGARD, Morten; RASMUSSEN, Lars, Kyhn; CLEMENTSON, Carl, Martin, Sebastian; (278 pag.)WO2019/115567; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

3335-98-6, 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. 3335-98-6 name is 1-Phenyloxindole, 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.

General procedure: A mixture of t-BuOK (1.63 g, 14.5 mmol) in EtOH (5.0 mL) was heated at 80 oC. Oxindole (10.0 mmol) was added, followed immediately by ethyl formate (1.09 mL, 13.5 mmol). Then, the reaction mixture was heated at 80 C for 5 min, and was cooled to 25 C. Crushed ice and H2O were added, then the mixture was acidified with 3 N HCl to pH = 3. The crude product was filtered and washed with water. Recrystallization from MeOH gave the pure product.

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

Reference:
Article; Liu, Yin-Li; Xu, Xiu-Hua; Qing, Feng-Ling; Tetrahedron; vol. 74; 40; (2018); p. 5827 – 5832;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

1914-02-9, A common heterocyclic compound, 1914-02-9, name is 3,3-Dimethylindoline, molecular formula is C10H13N, 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 a solution of 3- (chlorosulfonyl) benzoic acid (456 mg, 2.07 mmol, Aldrich) in CH2Cl2 (15 [ML)] was added DMF (15 [UL)] followed by oxalyl chloride (270 [; J, L,] 3.10 mmol). After stirring for 1.5 hours, the solvent and excess oxalyl chloride were removed by rotary evaporation. The residue was dissolved in toluene (15 mL), and [METHYL 2-AMINO-5-CYANOBENZOATE (370 MG,] 2.10 mmol) was added. The mixture was heated in a [105 C] oil bath for 2 hours, and the toluene was then removed by rotary evaporation. The residue was dissolved in [CH2CLZ] (6 mL), and a mixture of 3,3- [DIMETHYLINDOLINE,] descrinbed by Kucerovy et al. in Synth. Commun. 1992, 22 (5), 729- 733, (342 mg, 2.32 mmol) and triethylamine (600 [-LL,] 4.31 mmol) in [CH2C12] (6 [ML)] was added. This mixture was stirred overnight and then added to a separatory funnel with 100 mL of [CH2C12.] This solution was washed with 2 X 100 [ML] of 1 M aqueous HC1 and 100 [ML] of brine. The [CH2CK WAS] evaporated in the presence of silica gel, and the product was purified by chromatography using a Biotage Flash 40 M silica cartridge with a gradient from [CHUCK] to [1 % ETOAC] in [CH2C12 AS] eluent. Yield was 728 mg of white solid as the methyl ester. The methyl ester was hydrolyzed according to method D yielding 292 mg of white [SOLID. 1H] NMR (400 MHz, DMSO-d6) [8 12.] 57 (s, [1] H), 8. [80] (d, [J=] 8.7 Hz, [1 H),] 8.41-8. 44 (m, 2 H), 8.24 (d, [J=] 7.9 Hz, 1 H), 8.09- 8.14 (m, 2 H), 7.83 (t, J= 7.9 Hz, [1] H), 7.55 (d, J= 8.1 Hz, 1 [H),] 7.24 (t, J= 7.7 Hz, 1 H), 7.18 (d, [J=] 7.7 Hz, [1] H), 7.02 (t, [J=] 7.5 Hz, [1 H),] 3.73 (s, 2 H), 1. [08] (s, 6 H).

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

Reference:
Patent; PHARMACIA & UPJOHN COMPANY; WO2004/18414; (2004); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

3335-98-6, A common compound: 3335-98-6, name is 1-Phenyloxindole, 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.

General procedure: A mixture of isatins (1, 1.0 mmol), indolin-2-ones (2, 1.0 mmol) and ZrCl4 (23 mg, 0.1 mmol) was heated in anhydrous ethanol (5 mL) under reflux. After the disappearance of the reactants (8-12 h, monitored by TLC), the mixture was slowly cooled to room temperature. The red solids precipitated and were collected by filtration, then washed by a small amount of anhydrous ethanol to deliver pure compounds 3.

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-Phenyloxindole, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Liu, Meilin; Qiu, Shaozhong; Ye, Yu; Yin, Guodong; Tetrahedron Letters; vol. 57; 52; (2016); p. 5856 – 5858;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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

A solution of isoindolin-1-one (1.00 g, 7.51 mmol) in freshly-distilled THF (25 mL) was added slowly to a suspension of sodium hydride (450 mg, 11.26 mmol, freshly washed with hexane) in THF (25 mL) under N2 at 0 C and stirring was continued (30 min). To the reaction mixture was slowly added ethyl bromoacetate (1.24 mL, 11.26 mmol) and the resulting reaction mixture was allowed to stir at room temperature (16 h). The reaction mixture was quenched with methanol and concentrated. The obtained crude residue was further purified by gravity column chromatography (hexane/ethyl acetate, 2:1) provided pure 1 as an off-white solid (1.39 g, 78%); mp = 77-79C (Lit. mp = 78-80 C)1. 1H NMR (400 MHz, CDCl3) delta 7.87-7.85 (d, J = 7.6 Hz, 1H), 7.57-7.53 (m, 1H), 7.48-7.44 (m, 2H), 4.518 (s, 2H), 4.39 (s, 2H), 4.22 (q, J = 6.8 Hz, 2H), 1.28 (t, J = 6.8 Hz, 3H) ppm. The spectroscopic data was consistent with that previously reported.1

The synthetic route of 480-91-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Patil, Pravin C.; Luzzio, Frederick A.; Ronnebaum, Jarrid M.; Tetrahedron Letters; vol. 58; 38; (2017); p. 3730 – 3733;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

A common heterocyclic compound, 222036-66-0, name is 5-Aminoisoindolin-1-one, molecular formula is C8H8N2O, 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. 222036-66-0.

Intermediate 8 (50 mg, 0.162 mmol), 5-amino-2,3-dihydro-isoindol-l-one (72 mg, 0.485 mmol), glacial acetic acid (9 mul, 0.162 mmol) and n-butanol (1.5 ml) were combined and irradiated at 150 0C for 60 minutes in a Biotage 1-60 microwave reactor. The reaction was evaporated, purified by LCMS (low pH buffer) triturated with methanol and dried to give the title compound as a white solid (6 mg, 7percent). 1H NMR (400 MHz, DMSOd6) delta ppm 0.55 – 0.61 (m, 2 H), 0.87 – 0.93 (m, 2 H), 1.50 – 1.57 (m, 1 H), 1.64 – 1.77 (m, 3 H), 1.78 – 1.90 (m, 1 H), 1.91 – 2.00 (m, 2 H), 2.02 – 2.13 (m,2 H), 2.88 – 2.98 (m, 1 H), 3.09 – 3.16 (m, 2 H), 3.28 – 3.56 (m, 2 H), 4.38 (s, 2 H), 7.61 – 7.69 (m,3 H), 7.71 – 7.77 (m, 1 H), 7.86 – 7.91 (m, 1 H), 8.37 – 8.53 (m, 2 H), 10.39 (br. s, 1 H); m/z (ES+APCI)+: 421 [M+H]+.

The synthetic route of 5-Aminoisoindolin-1-one has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MEDICAL RESEARCH COUNCIL; WO2009/122180; (2009); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

1074-82-4, Adding some certain compound to certain chemical reactions, such as: 1074-82-4, name is Potassium 1,3-dioxoisoindolin-2-ide, 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 1074-82-4.

General procedure: To a solution of potassium 1,3-dioxoisoindolin-2-ide (1.85 g, 10.0 mmol), potassium iodide (0.08 g, 0.5 mmol) in acetone (25.0 mL), 1,2-dibromoethane dissolved in acetone (5.0 mL) was added by dropping funnel (3.72 g, 20.0 mmol), refluxed for 10 h. Monitored by TLC, and then filtered, concentrated by vacuum. The crude compound was purified by column chromatography on silica gel to give the desired intermediate 4 2-(2-bromoethyl) isoindoline-1,3-dione (1.83 g, 72.5% yield) 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 1074-82-4.

Reference:
Article; Xie, Ruliang; Mei, Xiangdong; Ning, Jun; Chemical and Pharmaceutical Bulletin; vol. 67; 4; (2019); p. 345 – 350;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding some certain compound to certain chemical reactions, such as: 104618-32-8, name is 2-(4-Oxocyclohexyl)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 104618-32-8. 104618-32-8

A. 2-[4-(4-Benzyl-1-piperazinyl)cyclohexyl]-1H-isoindole-1,3(2H)-dione To a solution of 2-(4-oxocyclohexyl)-1H-isoindole-1,3(2H)dione (3.78 g, 15.5 mmol), which was prepared according to the literature (J. Med. Chem., 1993, 1918), 1-benzylpiperazine (2.99 g/17.1 mmol) and AcOH (1.00 ml/17.1 mmol) in dichloroethane (50 ml) was added sodium triacetoxyborohydride (6.57 g/31.0 mmol) and the mixture was stirred for 2 days. The reaction mixture was poured into water (50 ml) and the mixture was extracted with dichloromethane (100 ml). The extract was washed with brine (50 ml), dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (NH2 gel/dichloromethane) to give a colorless oil (5.00 g/89%). 1H NMR (CDCl13) delta 7.86-7.65 (m, 4H), 7.35-7.28 (m, 5H), 4.25-4.10 (m, 1H), 3.52 (s, 2H), 2.73-2.40 (m, 8H), 2.20-2.08 (m, 1H), 1.80-1.35 (m, 8H) ppm.

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 2-(4-Oxocyclohexyl)isoindoline-1,3-dione.

Reference:
Patent; Ikeda, Takafumi; Kawamura, Mitsuhiro; Murase, Noriaki; Nukui, Seiji; Shishido, Yuji; Kawai, Makato; Okumura, Yoshiyuki; US2001/46993; (2001); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem