Author: Jessica.F

3339-73-9, name is 3-(1,3-Dioxoisoindolin-2-yl)propanoic 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. Application In Synthesis of 3-(1,3-Dioxoisoindolin-2-yl)propanoic acid

A mixture of phthalic anhydride and beta-alanine were heated to 190-200C in a sealed tube. Stirred for additional 30min at 190-200C after the solids totally melted. The reaction mixture was cooled to room temperature and 50% EtOH/water was added. The resulted suspension was filtered and the white precipitate was further washed with 50% EtOH/water, and then dried under vacuum overnight to give the N- phthaloyl-beta-alanine. Phosphoryl chloride was added to a suspension of N-phthaloyl- beta-alanine and phenylethylamine in acetionitrile. The suspension was stirred for 6h under reflux. Acetonitrile and phosphoryl chloride was removed by vacuum. The reaction mixture was then diluted with DCM and washed with sat NaHCC>3 solution, water and brine, then dried over anhydrous Na2S04. The filtrate was concentrated and the residue was purified by column chromatography using acetonitrile (0 to 20 %) in DCM as eluent to afford the imine compound. Acetic acid and sodium triacetoxyborohydride were added to a solution of imine compound in DCM and stirred for lh at room temperature. The reaction mixture was then washed with sat NaHCC>3 solution, water and brine, then dried over anhydrous Na2S04. The filtration was concentrated and the residue was purified by column chromatography using acetonitrile (0 to 50%) in DCM as eluent to give the amine compound. Cis-l ,2-Cyclohexanedicarboxylic anhydride was added to a solution of amine compound in p-xylene at 50C and stirred for 3h. The reaction mixture was concentrated under vacuum and the residue was purified by column chromatography using acetonitrile (0 to 20% with 1% AcOH) in DCM as eluent to give the designed product. Two diastereomers were separated by HPLC using water plus 0.1 %TFA and acetonitrile plus 0.1 %TFA as solvents.

The synthetic route of 3339-73-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY; THE BROAD INSTITUTE, INC.; HU, Longqin; MAGESH, Sadagopan; CHEN, Lin; LEWIS, Timothy; MUNOZ, Ben; WANG, Lili; WO2013/67036; (2013); A1;,
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Related Products of 132898-96-5,Some common heterocyclic compound, 132898-96-5, name is 2,3-Dioxoindoline-5-sulfonyl chloride, molecular formula is C8H4ClNO4S, 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.

Step 1: N-Benzyl-N-methyl-2,3-dioxoindoline-5-sulfonamide To a black solution of 2,3-Dioxo-2,3-dihydro-1H-indole-5-sulfonylchloride (4.00 g, 16.3 mmol) in 1:1 THF:CHCl3 was added, drop-wise via syringe pump, a solution of N-benzylmethylamine (2.73 mL, 21.2 mmol, 1.3 eq) and N,N-diisopropylethylamine (5.68 mL, 32.6 mmol, 2 eq) in CHCl3 (32 mL) over a period of 1.25 hr. with cooling in an ice bath. After stirring for 50 min. the reaction was allowed to warm to room temperature and stirred for 30 minutes. The reaction was concentrated. The crude product was purified on Biotage KP silica gel eluding with 98/2 CHCl2/CH3OH to give the analytically pure sample of the title compound as a bright yellow solid (0.18 g, 15% yield). Anal. Calc’d for C16H14N2O4S: C, 58.17; H, 4.27; N, 8.48; Found: C, 57.88; H, 4.36; N, 8.40; MS: (API-ES-) m/z 329 [M-H]. m.p.: 183-185 C.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2,3-Dioxoindoline-5-sulfonyl chloride, its application will become more common.

Reference:
Patent; Wyeth; US2005/250798; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 118289-55-7, name is 6-Chloro-5-(2-chloroethyl)indolin-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 118289-55-7, Recommanded Product: 6-Chloro-5-(2-chloroethyl)indolin-2-one

5-(2-(4-(1,2-benzisothiazol-3-yl)-piperazinyl)ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one A clean and dry 20-gallon glass lined tank was charged with 19 L of water and 4.44 Kg of sodium carbonate, after the carbonate had dissolved 4.29 Kg (17.5 moles) of 5-(2-chloroethyl)-6-chloro-oxindole and 3.62 Kg (1 6.5 moles) of 1-(1,2-benzisothiazol-3-yl) piperazine were added. The aqueous slurry was heated to reflux and the temperature maintained for 14 hours. When the reaction was complete the solution was cooled to 20 C. and filtered. The wet product was reslurried in 23 L of isopropyl alcohol at room temperature for 2 hours. The product was collected by filtration on 2 large Buchner funnels, each was washed with 3.4 L of fresh isopropyl alcohol. The product was vacuum dried at 30 to 40 C. until no isopropyl alcohol remained, giving 5.89 Kg (86.4% yield) of the desired free base which matched a standard sample by high performance liquid chromatography (HPLC).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Chloro-5-(2-chloroethyl)indolin-2-one, and friends who are interested can also refer to it.

Reference:
Patent; Pfizer Inc.; US5312925; (1994); A;,
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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. 611-09-6, name is 5-Nitroindoline-2,3-dione, A new synthetic method of this compound is introduced below., Computed Properties of C8H4N2O4

General procedure: A mixture of indole (2 mmol), isatin (1 mmol), SAMSNs (0.06 g), and water (3 ml) was stirred at 60 C for different periods of time as indicated in Table 4. After completion of the reaction (as monitored by TLC), the mixture was cooled to room temperature. The precipitated solid and the SAMSNs were filtered off and dissolved in acetone. After dissolution of the product, the solid catalyst was removed by filtration, and the resulting solution was evaporated under reduced pressure. The pure product was obtained by recrystallization from ethanol.

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:
Article; Mehrasbi, Ebrahim; Sarrafi, Yaghoub; Tajbakhsh, Mahmood; Research on Chemical Intermediates; vol. 41; 9; (2015); p. 6777 – 6787;,
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Electric Literature of 6872-06-6, 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. 6872-06-6 name is 2-Methylindoline, 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.

2-methylindoline (3.26 g, 24.5 mmol) and hexane (0.536 M, 45.7 ml) were placed in a 100 ml Schlenk flask. N-BuLi (1.1 eq, 10.8 ml) was added at -20 & lt; 0 & gt; C and allowed to stand at room temperature overnight. Filtered through glass frit (G4) and vacuum dried to obtain phosphine-amine lithium. The phosphine-amine lithium (3.37 g, 24.2 mmol) was added to diethyl ether (0.423 M, 57.3 ml) in a 250 ml Schlenk flask and CO 2 bubbling was performed at -78 C for 1 hour. THF (1.1 eq, 2.16 ml) and t-BuLi (1.1 eq, 15.7 ml) were added at -20 C and kept at this temperature for 2 hours. IPr2PCl (0.85 eq, 3.14 g) and diethyl ether (0.359 M, 57.3 ml) were added at the same temperature and maintained at the same temperature for 1 hour. After slowly reacting at room temperature overnight, 50 ml of distilled water was added at 0 C, followed by stirring at room temperature for 30 minutes. Work-up with diethyl ether, drying over MgSO4, and then red oil was obtained in 2.23 g, 37% yield via hexane, diethyl ether 50: 1 column.

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

Reference:
Patent; LG CHEM, LTD.; JANG, Jae Kwon; PARK, In Sung; KIM, Seul Ki; LEE, Eun Jung; LEE, Chong Hoon; HAN, Ki Won; HAN, Hyo Jung; (18 pag.)KR2017/68331; (2017); A;,
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Related Products of 2436-29-5,Some common heterocyclic compound, 2436-29-5, name is 3-(1,3-Dioxoisoindolin-2-yl)propanal, molecular formula is C11H9NO3, 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 mixture of (R)-(l-amino-but-3-ynyl)-7-chloro-3-phenylamino-3H-quinazolin-4-one (4.60 g, 12.2 mmol) and diisopropylethylamine (DIPEA) (5.5 ml) in dichloromethane (60 ml) was added a solution of 3-(l,3-dioxo-l,3-dihydro-isoindol-2-yl)-propionaldehyde (2.45 g, 12.1 mmol) in dichloroethane (10 ml), followed by a solution of sodium triacetoxy borohydride (NaBH(OAc)3) (0.25M in dichloroethane, 100 ml). The reaction mixture was stirred at room temperature and the reaction progress was monitored by HPLC/MS. Upon completion, a saturated sodium carbonate solution (100 ml) was added. The resulted organic layer was collected and washed with brine solution. The solvent was removed and residue was purified by flash column to afford 2- {3-[(R)- 1 -(7-chloro-4-oxo-3-phenylamino-3,4-dihydro-quinazolin-2-yl)-but-3- ynylamino]-propyl}-isoindole-l,3-dione (6.1 g, 95%) as off-white solid. M.p. 78-80 0C. LCMS: m/e 526 [M+H]. 1H NMR (DMSO-d6): delta 9.09 (s, br, IH), 8.07 (d, J= 8.8 Hz, IH), 7.74 (m, IH), 7.83-7.76 (m, 5H), 7.58 (dd, J= 8.8 and 2.0 Hz, IH), 7.17 (t, J= 7.6 Hz, 2H), 6.83 (brm, IH), 6.65 (m, 2H), 4.1 and 4.0 (s,s, br, IH, rotomers), 3.6 (t, J= 6.8Hz, 2H), 2.75 (s, br, 1 H), 2.67- 2.52 (brm, 2H), 2.35 (brm, 2H), 1.67 (brm, 2H).

The synthetic route of 2436-29-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ARQULE, INC.; WO2009/2808; (2008); A2;,
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. 603-62-3, name is 3-Nitrophthalimide, A new synthetic method of this compound is introduced below., Computed Properties of C8H4N2O4

a) Preparation of 6-nitrophthalamic acid:; A suspension of 57.6 g of 3-nitro-phthalimide (0.3 mol) in 672 g of water is cooled to 5C. 80 g of 30% sodium hydroxide solution (0.6 mol, 2 equivalents) are added in the shortest possible time. After 2 hours at 5C, the reaction mixture is added at 5C to 65 g of 32% hydrochloric acid solution (0.57 mol, 1.9 equivalents), which is diluted beforehand with 72 ml of water. The pH value is adjusted to 2-2.5 and the crude product which crystallises out is filtered off and washed twice with water. 6-Nitrophthalamic acid is obtained in a yield of 73%.

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; SYNGENTA PARTICIPATIONS AG.; SYNGENTA LIMITED.; WO2007/31323; (2007); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 20870-79-5,Some common heterocyclic compound, 20870-79-5, name is 5-Nitroindolin-2-one, molecular formula is C8H6N2O3, 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 suspension of 5-nitroindolin-2-one (5 g, 1 eq.) in EtOH(50 mL), activated carbon (1 g) and FeCl3 (1 g) were added.The mixture was heated to 78 C, and stirred for 10 min.Then 80% aqueous solution of hydrazine hydrate (8 eq.)was added dropwise into the reaction mixture in 5 min, theresulting mixture was stirred at 78 C for 8-10 h, thencooled to room temperature. The mixture was filtered to remove residue of activated carbon; the filtrate was concentratedunder vacuum to afford crude product, which waspurified by recrystallization from EtOH (about 15 mL) togive 5-aminoindolin-2-one as a pale yellow solid (yield91.9%).

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

Reference:
Article; Zhou, Yuanzheng; Ju, Yuan; Yang, Yang; Sang, Zitai; Wang, Zhenling; He, Gu; Yang, Tao; Luo, Youfu; Journal of Antibiotics; vol. 71; 10; (2018); p. 887 – 897;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 35197-64-9, name is 2-Bromo-4-(1,3-dioxoisoindolin-2-yl)butanoic acid, molecular formula is C12H10BrNO4, 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. Product Details of 35197-64-9

Example 373 (BVT056664); 2-{2-[2-(bicyclo [2.2. 1] hept-5-en-2-ylamino)-4-oxo-4, 5-dihydro-1, 3-thiazol-5-yl] ethyl}- I H-isoindole-1, 3 (2H)-dione; 2-bromo-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butanoic acid (0.204 g, 0.654 mmol) and N-bicyclo [2.2. 1] hept-5-en-2-ylthiourea (0.112 g, 0.666 mmol) were dissolved in acetone (15 ml) and heated to reflux for 8h. The reaction mixture was allowed to cool to room temperature. NaHCO3 (sat. solution) was added and extraction with DCM was performed. The organic phase was concentrated in vacuum to give the crude product (0.269 g) of which 10 mg was purified using preparative LC-MS (System C, 20-80% MeCN). 7mg, yield ‘H NMR (270 MHz, CHLOROFORM-D) 1.65-1. 84 (m, 4 H) 2.16-2. 37 (m, 1 H) 2.57-2. 73 (m, 1 H) 2.99-3. 11 (m, 2 H) 3.37 (t, J=4. 58 Hz, 1 H) 3.73-3. 88 (m, 1 H) 3.96-4. 12 (m, 1 H) 4.20 (dd, J=10. 27,3. 59 Hz, 1 H) 6.03-6. 10 (m, 1 H) 6.29 (dd, J=5. 69,2. 97 Hz, 1 H) 7.73- 7.81 (m, 2 H) 7.81-7. 91 (m, 2 H) MS (ESI+) for C2oHi9N303S/ 382 (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 35197-64-9, its application will become more common.

Reference:
Patent; BIOVITRUM AB; WO2005/75471; (2005); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 41910-64-9, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 41910-64-9, name is 4-Chloroindoline belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Step 2d: 2 ml of toluene, 90 mg of ethyl (1-cyclopropyl-4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate and, finally, dropwise, 0.55 ml of a 2M solution of trimethylaluminum in toluene are successively added to a solution of 113 mg of 4-chloroindoline in 4 ml of tetrahydrofuran. The reaction mixture is heated at 90 C. for 4 hours, and then cooled to ambient temperature, and 5 ml of methanol are added. After the addition of 10 g of silica, the reaction mixture is concentrated under reduced pressure. After purification by silica column chromatography (solid deposit), elution being carried out with a mixture of dichloromethane and methanol (100/0 then 98/02 V/V), 39 mg of 2-[2-(4-chloro-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-cyclopropyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one are obtained in the form of a white solid, the characteristics of which are the following:1H NMR spectrum (400 MHz): 0.83 (m, 2H); 1.07 (m, 2H); 2.69 (m, 1H); 3.18 (t, J=8.6 Hz, 2H); 3.36 (m, 4H); 3.55 (m, 4H); 4.18 (s, 2H); 4.23 (t, J=8.6 Hz, 2H); 5.27 (s, 1H); 7.09 (d, J=8.1 Hz, 1H); 7.21 (t, J=8.1 Hz, 1H); 7.98 (d, J=7.9 Hz, 1H)Mass spectrometry: method ARetention time Tr (min)=0.85;[M+H]+: m/z 415; [M-H]-: m/z 413

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

Reference:
Patent; SANOFI; Brollo, Maurice; Carry, Jean-Christophe; Certal, Victor; Didier, Eric; Doerflinger, Gilles; EL Ahmad, Youssef; Filoche-Romme, Bruno; Halley, Frank; Karlsson, Karl Andreas; Schio, Laurent; Thompson, Fabienne; US2013/274253; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem