Tag: M.W=200-300

Electric Literature of 193354-13-1,Some common heterocyclic compound, 193354-13-1, name is 5-Iodoindolin-2-one, molecular formula is C8H6INO, 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-[5-(5-Iodo-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrol-3-yl]-propionic acid 3-(2-Carboxyethyl)-2,4-dimethyl-5-formylpyrrole (97.5 mg), 130 mg 5-iodo-2-oxindole, and 75 muL piperidine in 3 mL of ethanol were heated at 95 C. for 5 hours. The reaction mixture was cooled and concentrated. The residue was suspended in 6 N aqueous hydrochloric acid. The precipitate was filtered, washed with water to pH 6 and dried in a vacuum oven overnight to give 155 mg (71%) of the title compound as an orange solid. 1H-NMR (360 MHz, DMSO-d6): delta 13.41 (s, br, 1H, NH-1′), 12.03 (s, br, 1H, COOH), 10.79 (s, br, 1H, NH-1), 8.12 (d, J=1.70 Hz, 1H, H-4), 7.65 (s, 1H, H-vinyl), 7.36 (dd, J=1.70, 7.93 Hz, 1H, H-6), 6.79 (d, J=7.93 Hz, 1H, H-7), 2.64 (t, J=7.76 Hz, 2H, CH2CH2COOH), 2.34 (t, J=7.76 Hz, 2H, CH2CH2COOH), 2.29 (s, 3H, CH3), 2.27 (s, 3H, CH3); MS m/z (relative intensity, %) 437 ([M+1]+, 100).

The synthetic route of 193354-13-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sugen, Inc.; US6395734; (2002); B1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 959235-95-1, name is 6-(Trifluoromethoxy)indoline, 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. Safety of 6-(Trifluoromethoxy)indoline

HATU (2.10 g, 5.52 mmol) was added to a mixture of 6-(trifluoromethoxy)indoline [CAS 953906-76-8] (747 mg, 3.68 mmol), 2-((3-(2-(terf-butoxy)ethoxy)-5-methoxy- phenyl)amino)-2-(4-chlorophenyl)acetic acid 3c (1 .5 g, 3.68 mmol) and diisopropylethylamine (1 .82 mL, 1 1 .03 mmol) in DMF (30 mL). The resulting mixture was stirred at room temperature for 12 h. The mixture was diluted with water and extracted with EtOAc. The organic layer was separated, dried over MgSO4, filtered and the solvent was evaporated under reduced pressure. Purification was carried out by flash chromatography on silica gel (15-40 muiotatauiota, 40 g, heptane/EtOAc 85/15). The pure fractions were combined and evaporated to dryness to give 2-((3-(2-(fe/t-butoxy)ethoxy)-5-methoxyphenyl)amino)-2-(4-chloro- phenyl)-1 -(6-(trifluoromethoxy)indolin-1 -yl)ethanone 3d (1 .33 g).

The synthetic route of 6-(Trifluoromethoxy)indoline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN PHARMACEUTICALS, INC.; KATHOLIEKE UNIVERSITEIT LEUVEN; BARDIOT, Dorothee Alice Marie-Eve; BONFANTI, Jean-Francois; KESTELEYN, Bart Rudolf Romanie; MARCHAND, Arnaud Didier M; RABOISSON, Pierre Jean-Marie Bernard; (76 pag.)WO2017/167953; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 675109-26-9,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.

General procedure: 5-Bromo-2-methylisoindolin-1-one (520 mg, 2.30 mmol) and thiophene-2-boronic acid (442mg, 3.45 mmol) were dissolved in a mixure of toluene (12 mL) and EtOH (6 mL). A solutionof 2 M Na2CO3 (3 mL) and Pd(dppf)Cl2 (94 mg, 0.12 mmol) were added and the entiremixture heated at reflux under N2 for 2 h. Additional thiophene-2-boronic acid (294 mg, 2.30mmol) was added and reflux continued under N2 overnight. Upon cooling, the mixture wasdiluted with water (100 mL) and extracted with CH2Cl2 (6×50 mL). The combined organicfractions were dried (Na2SO4), filtered, and the solvent removed under reduced pressure togive a crude solid which was purified by flash column chromatography on silica gel (EtOAcas eluant). The title compound was isolated as a light-brown solid (510 mg, 97%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6-Bromoisoindolin-1-one, its application will become more common.

Reference:
Article; Spicer, Julie A.; Miller, Christian K.; O’Connor, Patrick D.; Jose, Jiney; Huttunen, Kristiina M.; Jaiswal, Jagdish K.; Denny, William A.; Akhlaghi, Hedieh; Browne, Kylie A.; Trapani, Joseph A.; Bioorganic and Medicinal Chemistry Letters; vol. 27; 4; (2017); p. 1050 – 1054;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 118289-55-7,Some common heterocyclic compound, 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, molecular formula is C10H9Cl2NO, 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: Equimolar mixture of 6-chloro-5-(2-chloroethyl)-1,3-dihydro-2H-indol-2-one 1 (1.00mol) and the carbonyl compound (4i-x) (1.00mol) was stirred at RT in methanol (10mL) for 2h in presence of potassium carbonate (1.20mol). After completion, the reaction mass was filtered to remove inorganic salt, added methanol (10-20mL) and activated charcoal to the filtrate and stirred for 1hr. The crude product was filtered to remove charcoal, methanol was evaporated and cooled to 0-5C to get crude solid. Recrystallized using aqueous ethanol or methanol (Yield 60-70%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6-Chloro-5-(2-chloroethyl)indolin-2-one, its application will become more common.

Reference:
Article; Meti, Gangadhar Y.; Kamble, Atulkumar A.; Kamble, Ravindra R.; Somagond, Shilpa M.; Devarajegowda; Kumari, Sandhya; Kalthur, Guruprasad; Adiga, Satish K.; European Journal of Medicinal Chemistry; vol. 121; (2016); p. 221 – 231;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 205383-87-5, 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. 205383-87-5 name is tert-Butyl 2-oxospiro[indoline-3,3′-pyrrolidine]-1′-carboxylate, 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.

Step A: tert-butyl 5 -chloro-2-oxospiro [indoline-3 ,3 ?-pyrrolidinel- 1 ?-carboxylateTo a stirred solution tert-butyl 2-oxospiro[indoline-3,3?-pyrrolidine]-i?-carboxylate (800 mg,2.77 mmol) in dichioromethane (40 mL) and DMF (4 mL) was added N-chlorosuccinimide and the mixture was allowed to stir at room temperature overnight. Aqueous NaHCO3 was added and the mixture was extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by ISCO (40g, EtOAc/Hex= 1 / 1) to give tert-butyl 5 -chloro-2-oxospiro [indoline-3 ,3 ?-pyrrolidine]- 1 ?-carboxylate. [M+ 1] =324.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, tert-Butyl 2-oxospiro[indoline-3,3′-pyrrolidine]-1′-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LIM, Yeon-Hee; GUO, Zhuyan; ALI, Amjad; EDMONDSON, Scott, D.; LIU, Weiguo; GALLO-ETIENNE, Gioconda, V.; WU, Heping; GAO, Ying-Duo; STAMFORD, Andrew, M.; YU, Younong; KEVIN, Nancy, J.; ANAND, Rajan; SHA, Deyou; NEELAMKAVIL, Santhosh, F.; HUSSAIN, Zahid; KUMAR, Puneet; MONINGKA, Remond; DUFFY, Joseph, L.; XU, Jiayi; JIANG, Yu; SONE, Hiroki; CHAKRABARTI, Anjan; (183 pag.)WO2015/164308; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 552330-86-6, These common heterocyclic compound, 552330-86-6, name is 5-Bromoisoindolin-1-one, 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.

5-Bromo-2,3-dihydro-lH-isoindol-l-one (100 mg, 0.47 mmol) was dissolved in DMF (4.7 mL) and stirred at 0C. NaH (38 mg, 0.94 mmol, 60 wt.% dispersion in oil) was carefully added in two portions, and the resulting mixture was allowed to stir at 0C for 15 minutes before 2,2,2-trifluoroethyl trifluoromethanesulfonate (110 mg, 0.47 mmol) was added. The mixture was allowed to stir at 0C for 30 minutes before saturated aqueous NaHC03 (10 mL) was carefully added, and the mixture was extracted with EtOAc. The organic layer was washed with water, brine, dried over anhydrous MgS04, filtered, and concentrated in vacuo. The residue was purified by silica chromatography, eluting with a 0-20% EtOAc/hexanes gradient. LRMS (ESI) calc’d for Ci0H8BrF3NO [M+H]+: 294, found: 294.

Statistics shows that 5-Bromoisoindolin-1-one is playing an increasingly important role. we look forward to future research findings about 552330-86-6.

Reference:
Patent; MERCK SHARP & DOHME CORP.; DINSMORE, Christopher; FULLER, Peter; GUERIN, David; THOMPSON, Christopher F.; PU, Qinglin; SCOTT, Mark E.; KATZ, Jason David; KURUKLASURIYA, Ravi; CLOSE, Joshua T.; FALCONE, Danielle; BRUBAKER, Jason; ZENG, Hongbo; BAI, Yunfeng; FU, Jianmin; KONG, Norman; LIU, Yumei; ZHENG, Zhixiang; WO2014/146492; (2014); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 1035235-27-8, 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. 1035235-27-8 name is tert-Butyl 4-bromoisoindoline-2-carboxylate, 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.

Example 136 r(S)-1-(2.4-Difluoro-3-phenoxy-phenyl)-propy|1-(2,3-dihydro-1 H-isoindol-4-yl)-am hydrochlorideStep 1 A solution of Key Intermediate 1 (50 mg, 0.19 mmol), fe -butyl 4- bromoisoindoline-2-carboxylate (57 mg, 0.19 mmol) and sodium fe -butoxide (26 mg, 0.27 mmol) in dioxane (1 ml) was degassed by bubbling through nitrogen for 5 mins. Tris(dibenzylideneacetone)dipalladium (0) (5 mg) and 2,2′-bis(diphenylphosphino)-1 ,1 ‘- binapthyl (5 mg) were added and the reaction mixture was heated to 120 C for 20 mins under microwave irradiation. The mixture was partitioned between sat. sodium hydrogen carbonate and ethyl acetate. The organic fractions were washed with brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by preparative hplc to give 4-[(S)-1-(2,4-difluoro-3-phenoxy-phenyl)-propylamino]-1 ,3-dihydro-isoindole-2- carboxylic acid tert-butyl ester (23 mg) as a solid.

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

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; WOODHEAD, Andrew, James; CHESSARI, Gianni; BESONG, Gilbert, Ebai; CARR, Maria, Grazia; HISCOCK, Steven, Douglas; O’BRIEN, Michael, Alistair; REES, David, Charles; SAALAU-BETHELL, Susanne, Maria; WILLEMS, Hendrika, Maria, Gerarda; THOMPSON, Neil, Thomas; WO2013/64538; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 3416-57-7, name is 2-(2-Oxopropyl)isoindoline-1,3-dione, A new synthetic method of this compound is introduced below., Recommanded Product: 2-(2-Oxopropyl)isoindoline-1,3-dione

N-acetonylphthalimide (1 g, 4.9 mmol) was dissolved in DMF-DMA (20 mL),Add some 4A molecular sieves.The reaction mixture was stirred at 100C under nitrogen atmosphere for 15 hours.Cooled to room temperature and filtered to give crude solid (E)-2-(4-(dimethylamino)-2-oxo-3-butenyl)isoindoline-1,3-dione (600 mg) 47.5%).

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; BEIGENE, LTD; WANG, ZHIWEI; GUO, YUNHANG; (300 pag.)TWI602818; (2017); B;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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 5332-26-3 as follows. COA of Formula: C9H6BrNO2

General procedure: S-alkylation of the products was achieved by following a modified method [38]. The oxadiazoles (6a, 6b, 13) (0.02, mol) and K2CO3 (0.022, mol) were stirred in 10mL of acetone for 20 mints followed by the addition of alkyl bromides 7a-c and 7d-m (0.022, mol). The reaction mixture was stirred for 4-6h at room temperature. The reaction mixture was concentrated under vacuum and crude solid gained was recrystallized from methanol to get pure products. 8a: Colorless solid; 55% yield; Rf: 0.55 (chloroform: acetone, 9:1), m.p.; 224-226C; 1H NMR (300MHz, DMSO-d6): delta ppm 10.71 (s, 1H, NH), 7.91-7.84 (m, 4H, Ar-H), 7.64 (dd, 4H, J=18, 9Hz, Ar-H), 7.28 (d, 2H, J=9Hz, Ar-H), 7.06 (d, 2H, J=9Hz, Ar-H), 5.28 (s, 2H, SCH2N), 2.31 (s, 3H, Ar-CH3); 13C NMR (75MHz, DMSO-d6): delta ppm 167.02, 166.74, 160.01, 144.00, 142.03, 140.01, 135.44, 131.76, 129.72, 127.89, 126.94, 124.06, 119.95, 118.11, 43.00, 21.37; IR (cm-1) 3260 (N-H), 3025 (C-H, aromatic), 2948 (C-H, aliphatic), 1716 (C=O), 1602 (C=N), 1308, 1176 (O=S=O); Anal. Calcd for C24H18N4O5S2: C, 56.91; H, 3.58; N, 11.06; O, 15.79; S, 12.66 Found: C, 56.98; H, 3.61; N, 11.11; O, 15.79; S, 12.72.

According to the analysis of related databases, 5332-26-3, the application of this compound in the production field has become more and more popular.

Reference:
Article; Batool, Farwa; Hamdani, Syeda Shamila; Hameed, Shahid; Khan, Bilal Ahmad; Mughal, Ehsan Ullah; Saeed, Muhammad; Saleem, Hafiza Nosheen; Bioorganic Chemistry; vol. 96; (2020);,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 5332-26-3,Some common heterocyclic compound, 5332-26-3, name is 2-(Bromomethyl)isoindoline-1,3-dione, molecular formula is C9H6BrNO2, 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 8: 6-((R)-5-{[((RS)-2-methoxy-8,9-dihydro-furo[2,3-Lambda]quinolin-9-ylmethyl)- amino] -methyl}-2-oxo-oxazolidin-3-yl)-4H-benzo [ 1 ,4] thiazin-3-one:; 8.i. rac-3-( 1 ,3-dioxo- 1 ,3-dihydro-isoindol-2-yl)-2-(7-fluoro-2-methoxy-quinolin-8-yl)- propionic acid methyl ester:; To a solution of LiEtaMDS (IM in TEtaF, 9.6 niL) was added at -78C a solution of (7-fluoro-2-methoxy-quinolin-8-yl)-acetic acid methyl ester (2.0 g, 8.0 mmol; prepared as in WO 2007/081597) in TEtaF (16 mL) over lO min. After stirring the resulting orange mixture for 1 h at -78C, a solution of Lambda/-(bromomethyl)phthalimide (1.2 eq.) in TEtaF (16 mL) was added dropwise over 10 min. The mixture was stirred 1 h at -78C and then at it overnight. The yellow solution was quenched with 17V EtaC1 (80 mL) and then extracted with DCM. The combined org layers were washed with water, dried over MgSO4, concentrated and purified by CC (Etaept/EA 1 : 1) to give 1.89 g of a yellow solid which was recrystallized from EA/MeOEta/NEta4OEta (90:10:1) to afford the title intermediate as a colourless solid (924 mg, 28% yield). MS (ESI, m/z): 409.3 [IVB-H+].

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

Reference:
Patent; ACTELION PHARMACEUTICALS LTD; HUBSCHWERLEN, Christian; RUEEDI, Georg; SURIVET, Jean-Philippe; ZUMBRUNN ACKLIN, Cornelia; WO2010/15985; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem