Author: Jessica.F

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. 169037-23-4, name is 5-(Trifluoromethoxy)indoline-2,3-dione, A new synthetic method of this compound is introduced below., Quality Control of 5-(Trifluoromethoxy)indoline-2,3-dione

General procedure: A mixture of bisarylidenepiperidin-4-one (1.36 mmoL), isatin (2.72 mmoL) and L-phenylalanine (2.72 mmoL) were heated with stirring in [bmim]Br medium (3 mL) for 1 h at 100 C. After completion of the reaction (TLC), ethyl acetate (2 x 5 mL) was added and the reaction mixture was stirred for 10 min. The organic layer was removed under reduced pressure and the crude product was purified by column chromatography (ethyl acetate:hexane v/v 3:7). 5′-Benzyl-4′-phenyl-5-(trifluoromethoxy)spiro[3,2′]oxindolopyrrolidino-4′-phenyl-1?-styryl-5-benzylidenespiro[3′.3?]piperidin-4?-one (5a): Melting point 210-212 C; white solid, 94%; 1H-NMR (CDCl3, 400 MHz): delta/ppm 5.00 (d, J = 14.64 Hz, 1H), 4.68-4.72 (m, 1H), 4.34 (d, J = 10.24 Hz, 1H), 3.80 (d, J = 13.92 Hz, 1H), 3.68 (d, J = 16.92 Hz, 1H), 3.47 (d, J = 5.4 Hz, 1H), 3.02 (d, J = 11.72 Hz, 1H), 2.72-2.77 (dd, J = 13.96, 8.08 Hz, 1H), 2.54 (d, J = 13.92 Hz, 1H), 6.56-6.63 (m, 2H), 6.92-7.42 (m, 23H, Ar); 13C-NMR (CDCl3, 100 MHz): delta/ppm 39.6, 47.3, 52.8, 53.1, 61.0, 67.3, 70.8, 100.9, 109.7, 121.1, 122.5, 124.1, 124.4, 126.4, 127.3, 128.5, 128.6, 128.7, 128.8, 129.3, 129.6, 130.1, 130.4, 134.5, 136.9, 138.3, 138.4, 138.7, 139.7, 139.8, 144.4, 179.8, 197.1. EI-MS: m/z 711 (M+). Anal. Calcd for C44H36F3N3O3: C, 74.25; H, 5.10; N, 5.90. Found: C, 74.38; H, 5.17; N, 5.81.

The synthetic route of 169037-23-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Arumugam, Natarajan; Almansour, Abdulrahman I.; Kumar, Raju Suresh; Govindasami, Periyasami; Al-thamili, Dhaifallah M.; Krishnamoorthy, Rajapandian; Periasamy, Vaiyapuri Subbarayan; Alshatwi, Ali A.; Mahalingam; Thangamani, Shankar; Menendez, J. Carlos; Molecules; vol. 23; 5; (2018);,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

102359-00-2, name is 2-Oxoindoline-5-carboxylic Acid, belongs to indolines-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Computed Properties of C9H7NO3

General procedure: A solution of 9a-d (2 mmol), EDCI (3 mmol) and HOBt (3 mmol) in dry DCM (20 mL) was stirred at 0C for 3.5 h. Then different substituted amines (2.2 mmol) and DIPEA (4 mmol) were added and the reaction was stirred at r.t. for another 1.5 h. The organic layer was washed with water and brine and dried over Na2SO4. Removal of the solvent gave a residue that was purified by column chromatography (silica gel, CH2Cl2-MeOH 100: 1 as an eluent) to furnish 10a-n as white solids.

The synthetic route of 102359-00-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Guo, Jing; Zhu, Mingyue; Wu, Tianxiao; Hao, Chenzhou; Wang, Kai; Yan, Zizheng; Huang, Wanxu; Wang, Jian; Zhao, Dongmei; Cheng, Maosheng; Bioorganic and Medicinal Chemistry; vol. 25; 13; (2017); p. 3500 – 3511;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 496-12-8,Some common heterocyclic compound, 496-12-8, name is Isoindoline, molecular formula is C8H9N, 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 stirred solution of Boc-2,4-dichloro-d-phenylalanine (0.280 g, 0.84 mmol), EDC¡¤HCl (0.161 g, 0.84 mmol), HOBt (0.170 g, 1.26 mmol) and DIPEA (1.12 mL, 6.29 mmol) in DMF (2.0 mL), isoindoline (0. 10 g, 0.84 mmol) was added. The reaction was stirred at room temperature for 24 h. Upon completion, solvent was removed under reduced pressure and the crude was purified using column chromatography to provide desired coupled product in 78% yield. To the purified compound (0.21 g, 0.48 mmol) was added 1 M HCl (9.5 mL, 1 M in Et2O). After 4 h of stirring, the solvent was removed under reduced pressure to afford target compound 4 as a white solid. 1H NMR (400 MHz, CD3OD): delta 3.42 (d, 2H, 8.0 Hz), 4.24 (d, 1H, 12 Hz), 4.63 (t, 1H, 8.0 Hz), 4.72 (d, 1H, 16 Hz), 4.89 (d, 1H, 16 Hz), 5.00 (d, 1H, 12 Hz), 7.26 (m, 1H), 7.35 (m, 4H), 7.44 (d, 1H, 8.0 Hz), 7.54 (d, 1H, 4.0 Hz) 13C NMR (100.6 MHz, CD3OD): delta 35.3, 52.1, 53.2, 53.6, 123.7, 123.9, 128.9, 129.1, 129.2, 130.7, 132.1, 132.4, 136.0, 136.3, 136.4, 136.6, 168.1 HRMS (TOF-MS) Exact mass calcd for C17H16Cl2N2O [M+H]+: 335.0718, found: 335.0712.

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

Reference:
Article; Whitehead, Lewis; Dobler, Markus R.; Radetich, Branko; Zhu, Yanyi; Atadja, Peter W.; Claiborne, Tavina; Grob, Jonathan E.; McRiner, Andrew; Pancost, Margaret R.; Patnaik, Anup; Shao, Wenlin; Shultz, Michael; Tichkule, Ritesh; Tommasi, Ruben A.; Vash, Brian; Wang, Ping; Stams, Travis; Bioorganic and Medicinal Chemistry; vol. 19; 15; (2011); p. 4626 – 4634;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

337536-15-9, name is 4-Bromoisoindolin-1-one, belongs to indolines-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. name: 4-Bromoisoindolin-1-one

General procedure: Example 1 4-[1-(3-chloro-4-fluorophenyl)-5-(3-chloro-5-fluorophenyl)-1H-pyrazole-3-yl]-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-1-one Step 4 [0522] 100 mg (0.25 mmol) of the product from step 3 is dissolved in 5 ml of dioxane and mixed with 75 mg (0.30 mmol) bis-pinakolato-diboron, 73 mg (0.74 mmol) potassium acetate and 12 mg (0.02 mmol) [1,1-bis-(diphenylphosphino)ferrocene]-dichloropalladium dichlormethane complex. The reaction mixture is stirred for 1 hour in the microwave at 120 C., cooled down to RT, mixed with 63 mg (0.37 mmol) of the compound from example 22A, 0.25 ml sodium carbonate solution (2 N in water, 0.50 mmol) and 10 mg (0.01 mmol) [1,1-bis-(diphenylphosphino)ferrocene]-dichloropalladium-dichlormethane complex and mixed for 2 hours at 120 C. The reaction mixture is filtered through a Millipore syringe filter, mixed with DMSO, and separated twice using preparative HPLC (solvent: acetonitrile/water gradient). This produces 42 mg (37% of theoretical yield) of the title compound. Example 3 4-[1-(3-chloro-4-fluorophenyl)-5-(3-chloro-5-fluorophenyl)-1H-pyrazole-3-yl]-2,3-dihydro-1H-isoindole-1-one [0533] [0534] The synthesis of the title compound is performed starting from 100 mg (0.25 mmol) of the product from step 3 of example 1 in a manner analogous to the synthesis of the compound from example 1. In step 4, instead of the compound from example 22A, 4-bromo-2,3-dihydroisoindol-1-on (63 mg, 0.30 mmol) is used. The result is 74 mg (65% of theoretical yield) of the title compound. [0535] 1H-NMR (400 MHz, DMSO-d6): delta=4.72 (s, 2H), 7.21 (dt, 1H), 7.32-7.41 (m, 2H), 7.49 (s, 1H), 7.51-7.58 (m, 2H), 7.62 (t, 1H), 7.71 (d, 1H), 7.83 (dd, 1H). [0536] LC-MS (Method 1): Rt=1.28 min; MS (ESIpos): m/z=456 [M+H]+.

The synthetic route of 337536-15-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AICURIS GMBH & CO. KG; Wildum, Steffen; Klenke, Burkhard; Wendt, Astrid; US2015/203500; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 446292-08-6, These common heterocyclic compound, 446292-08-6, name is (S)-2-((2-Oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-yl)methyl)isoindoline-1,3-dione, 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.

100 g (S)-2-((2-oxo-3-(4-(3-oxo-morpholino)phenyl)oxazolidin-5-yl)methyl)isoindoline-1,3-dione of Formula (I), 1000 ml methanol and 119 g methyl amine were added to RBF at 25 C. to 35 C. The reaction was heated to 60 C. to 65 C. for 1-2 hours. To the reaction mass succinic acid (15 g) was added till to pH 5.5 to 6.0 and maintained for 30 minutes. The reaction mass was cooled to 45 to 50 C. and maintained for 30 minutes. The reaction mass was cooled to 25 to 35 C. and maintained for 30 minutes. The product was filtered and washed with methanol (50 ml*2) afforded succinate salt of (S)-4-(4-(5-(aminomethyl)-2-oxo-oxazolidin-3-yl)phenyl)morpholin-3-one of Formula (JS).

The synthetic route of 446292-08-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CADILA HEALTHCARE LIMITED; Dwivedi, Shriprakash Dhar; Prasad, Ashok; Pal, Daya Ram; Sharma, Mukul Hari Prasad; Jain, Kuldeep Natwarlal; Patel, Naitik Bharatbhai; US2014/378682; (2014); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 239463-85-5, name is (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate, 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 239463-85-5, Recommanded Product: (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate

3- {5 – [(2R) -2-aminopropyl] -7-cyano-2,3-dihydro -1H- indol-1-yl} propyl benzoate (2R, 3R) – mono tartrate 50g(97.5mmol, 1eq ) was poured into methanol 500ml, potassium hydroxide 12g (214mmol, 2.2eq)was reflux for 2 hours stirring was charged. After completion of the reaction, after cooling to room temperature filtered, the filtrate was concentrated (R)-5-(2-aminopropyl) -1- (3-hydroxypropyl) indoline-7-carbonitrile 25 g (100%) It was obtained.

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, (R)-3-(5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate (2R,3R)-2,3-dihydroxysuccinate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Kyongbo Pharm Company Limited; Son, Feju; Ban, Sonfun; Kwon, Hyok Bom; Yoon, Ik Hwan; Choi, Min-sik; Yang, Jiwon; (15 pag.)JP2016/23186; (2016); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 1677-48-1, These common heterocyclic compound, 1677-48-1, name is 5,6-Dichloroindoline-2,3-dione, 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.

5,6-Dichloro-7-nitroisatin (13i) was obtained in 51% yield from 5,6-dichloroisatin (13g) by using a similar procedure as that for 13h. Mp 200-201 C.; IR: 1784, 1759, 1743, 1626, 1547, 1442, 1332 cm-1; 1 H NMR delta 11.934 (s, 1H), 8.125 (s, 1H); HRMS Calcd for C8 H2 Cl2 N2 O4: 259.9391; Found: 259.9384.

The synthetic route of 1677-48-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; State of Oregon, Acting by and through the Oregon State Board of Higher Education, Acting for and on Behalf of the Oregon Health Sciences University and the University of Oregon; Acea Pharmaceuticals, Inc.; The Regents of the University of California; US5597922; (1997); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-2-one, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 118289-55-7

EXAMPLE 3; 5-(2-(4-Benzo[d]isothiazol-3-yl)piperazin-1-yl)ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one hydrochloride. (I); A reactor is loaded with 131 g (0.57 mol) of 6-chloro-5-(2-chloro-ethyl)-1,3-dihydro-indol-2-one, 125 g (0.57 mol) of piperazinyl benzoisothiazole, 260 ml of dimethylsulfoxide, 26 ml of water and 4.3 g (0.0285 mols) of Nal. The reaction mixture is added with 103 g (0.969 mol) of Na2CO3, with stirring under nitrogen atmosphere. The resulting mixture is heated to about 115-125 C. in 1 h and kept at said temperature under stirring for approx. 1 hr 45 min, then cooled and slowly added in about 25 min with isopropyl alcohol (650 ml), at a temperature of about 110 C., then slowly cooled at 25 C. The filtrate and the precipitate are washed with isopropyl alcohol (2¡Á130 ml) to obtain 310 g of 5-(2-(4-benzo[d]isothiazol-3-yl) piperazin- 1-yl)ethyl)-6-chloro- 1,3-dihydro-2H-indol-2-one free base, as a crystalline solid. The resulting product is placed in a 3 L beaker with 1500 ml of purified water, and 150 ml of 32% HCl are dropped therein with stirring. The reaction mixture is kept under stirring for 10 min, filtered, washed with purified water (2¡Á500), dried to give 260 g of 5-(2-(4-benzo[d]isothiazol-3-yl) piperazin- 1-yl)ethyl)-6-chloro- 1,3-dihydro-2H-indol-2-one hydrochloride, as a crystalline solid.

According to the analysis of related databases, 118289-55-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; DIPHARMA S. P. A.; LUNDBECK PHARMACEUTICALS ITALY S. P. A.; US2007/117810; (2007); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 85342-65-0, 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. 85342-65-0, name is 4,5,6,7-Tetrachloro-2-hydroxyisoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: A screw-capped culture tube with a stir bar was charged with alkyl carboxylic acid (0.2 mmol), /V-hydroxyphthalimide or tetrachloro-/V-hydroxyphthalimide (0.2 mmol, 1 .0 equiv) and Lambda/,Lambda/’-dicyclohexylcarbodiimide (0.2 mmol, 1 .0 equiv). The tube was then evacuated and backfilled with argon for three times. CH2CI2 (2.0 mL) was added and the resulting mixture was stirred at room temperature for 2 h before the volatiles were removed in vacuo. MgBr2 – OEt2 (77 mg, 0.3 mmol, 1 .5 equiv) was added. The tube was evacuated and backfilled with argon for three times. Suspension A (0.8 mL, NiCI2 – 6H20 (10 mol%)/L1 (13 mol%) in THF) or suspension C (0.8 mL, NiCI2 – 6H20 (10 mol%)/L2 (13 mol%) was added. The mixture was stirred vigorously at room temperature for 15 min (or until no granular MgBr2 OEt2 was observed) and was subsequently cooled to 0 C before a suspension of [B2pin2Me]Li in THF (1 .1 mL) was added in one portion (note: do not add it dropwise). After being strred for 1 h, the reaction was warmed to room temperature and stirred for another 1 h. The reaction mixture was then quenched with 0.1 N HCI (10 mL) and extracted with Et20 (5 mLx2). The combined organic layers were dried over Na2S04, concentrated in vacuo and purified by column chromatography to give the desired product.

The chemical industry reduces the impact on the environment during synthesis 4,5,6,7-Tetrachloro-2-hydroxyisoindoline-1,3-dione. I believe this compound will play a more active role in future production and life.

Reference:
Patent; THE SCRIPPS RESEARCH INSTITUTE; BARAN, Phil; LI, Chao; WANG, Jie; CHATTERJEE, Arnab, Kumar; KUMAR, Manoj; YU, Shan; JOHNSON, Kristen, Ann; QIN, Tian; SHANG, Ming; (167 pag.)WO2018/175173; (2018); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 3676-85-5, 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. 3676-85-5 name is 5-Aminoisoindoline-1,3-dione, 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 76 N-Cyclohexylmethyl-N’-(1,3-dioxo-2,3-dihydro-1H-5-isoindolyl)urea Diphenylphosphoryl azide (232 mg, 0.85 mmol, 1.2 eq) and triethylamine (85 mg, 0.85 mmol, 1.2 eq) were added to a solution of cyclohexylacetic acid (100 mg, 0.70 mmol) in toluene, and the mixture was stirred at 110C for 60 min. Thereafter, 4-aminophthalimide (114 mg, 0.70 mmol, 1.0 eq) and a minor amount of DMF were added thereto, and the mixture was stirred at 110C for 150 min. After the completion of the reaction, the reaction solution was poured into water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine and was dried over sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The residue was purified by a preparative TLC [chloroform-acetone] to give the title compound as a crystal (46 mg, 21.7%). MS m/z: 301 1H-NMR delta: 0.85 – 0.96 (2H, m), 1.07 – 1.26 (3H, m), 1.35 – 1.47 (1H, m), 1.58 – 1.73 (5H, m), 2.97 (2H, t, J = 6.22 Hz), 6.42 (1H, t, J = 5.73 Hz), 7.56 (1H, dd, J = 1.95, 8.29 Hz), 7.66 (1H, d, J = 8.30 Hz), 8.01 (1H, d, J = 1.71 Hz), 9.11 (1H, s), 11.06 (1H, s)

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Aminoisoindoline-1,3-dione, and friends who are interested can also refer to it.

Reference:
Patent; KIRIN BEER KABUSHIKI KAISHA; EP1256574; (2002); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem