Tag: M.W=300-400

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. 88150-75-8, name is Ethyl 4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Safety of Ethyl 4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate

Preparation of ETHYL 2-(2-CHLOROBENZYLIDINE)-4-[2-(PHTHALIMIDE) ETHOXY] ACETOACETATE (XV : A 250 mL two-necked flask, equipped with a magnetic stirring bar and thermometer was charged with 10 g of ethyl 4- [2- (phthalimido) ethoxy] acetoacetate and 3.96 g 2- chlorobenzaldehyde and 100 mL isopropanol under nitrogen atmosphere. To the resulting mixture was added 0.188 ML of acetic acid and 0.223 ML pyrolidine. The reaction mixture was heated to 37 C and stirred at this temperature for 5 hours. The solvent was removed in vacuo and the residue was dissolved in 100 ML of methylene chloride. The resulting solution was washed with 100 mL of sat. NAHCO3 and 100 mL of water, dried over 5 G OF MGS04. MGS04 was filtered off, the filtrate was concentrated in vacuo. The residue was purified by flash chromatography using ethyl acetate/hexane (20/80) as an eluent to give 7.72 g of ethyl 2- (2-CHLOROBENZYLIDINE)-4- [2- (PHTHALIMIDE) ethoxy] acetoacetate as an light brown oil (yield 56%, rel. compound purity > 98%). 1H-NMR (CDCL3) No. 7.89 (s, 1H), 7.78 (dd, 2H), 7.69 (dd, 2H), 7.35 (M, 1H), 7.28 (M, 2H), 7.17 (M, 1H), 4.44 (s, 2H), 4.05 (Q, 2H), 3.76 (T, 2H), 3.64 (t, 2H), 1.20 (t, 3H). 13C-NMR (CDCI3) 6 203. 2,168. 4,164. 0,140. 0,134. 0,133. 9,132. 3,131. 5, 130.4, 129.8, 127.3, 126.8, 123.4, 77.7, 68.5, 62.0, 37.4, 14.3.

The synthetic route of 88150-75-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; EOS ECZACIBASI OZGUN KIMYASAL URUNLER SANAYI VE TICARET A.S.; WO2004/58711; (2004); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 356068-93-4, 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. 356068-93-4 name is (Z)-5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid, 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.

To a stirred solution of compound 1 (0.5 g, 1.67 mmol) in DMF (35 rnL) at room temperature was added etaOBt (1.02 g, 7.52 mmol), triethylamine (2.12 mL, 15.03 mmol), ECDIetaC1 (1.44 g, 1.52 mmol) and methyl 6-aminohexanate hydrochloride(0.91 g, 5.0 mmol) successively. The mixture was stirred for 24 h at room temperature and then was diluted with water (20 mL), brine (20 mL) and saturated bicarbonate solution (20 mL) and the peta of solution was adjusted to 11-12 with 10 M NaOH. The mixture was filtrated and the resulting solid was washed with water and dried to obtain crude yellow solid product 110-4 (0.47 g, 65.8%). LCMS: m/z 428(M+1), 1H NMR(DMSO-J6) deltal.33 (m, 2eta), 1.54 (m, 4H), 2.32 (t, 2H), 2.42(s, 3H), 2.50(s, 3H), 3.20( t, 2H), 3.59 (s, 3H), 6.85 (m, 2H), 7.60 (t, IH), 7.69 (s, IH), 7.71 (m, IH), 10.88 (s, IH), 13.67 (s, IH).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, (Z)-5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; CURIS, INC.; WO2008/33747; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 17702-83-9, name is 2-(8-Bromooctyl)isoindoline-1,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. category: indolines-derivatives

General procedure: Procedure M2. A mixture of the appropriate 2-(bromoalkyl)-isoindoline-1,3-dione (1 equiv)with 1,2,3,4-tetrahydoisoquinoline (1 equiv) in the presence of K2CO3 (2.5-3 equiv) was stirred inacetonitrile under reflux for 20 h. Subsequently, the solvent was evaporated under vacuum, producinga residue which was further dissolved in 40 mL of sodium bicarbonate and extracted with ethyl acetate(3 x 30 mL). The organic layer was acidified 2 M HCl and extracted with distilled water (3 x 30 mL).Then, the combined aqueous extracts were alkalized using 4M NaOH, extracted with DCM and driedwith anhydrous Na2SO4. The solvent was then evaporated and the residue was purified by silica gelcolumn chromatography (S4) yielding a yellow oil. The final product was obtained in the form ofhydrochloride salt. The following compounds were obtained.

The synthetic route of 17702-83-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Hebda, Michalina; Bajda, Marek; Wieckowska, Anna; Szal?aj, Natalia; Pasieka, Anna; Panek, Dawid; Gody?, Justyna; Wichur, Tomasz; Knez, Damijan; Gobec, Stanislav; Malawska, Barbara; Molecules; vol. 21; 4; (2016);,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 1168150-46-6,Some common heterocyclic compound, 1168150-46-6, name is (E)-Methyl 3-(methoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate, molecular formula is C18H15NO4, 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: A mixture of intermediate (3a, 3b, 6a, 6b, 10a, 10b, 11a-d, and14a-g, 1.5 mmol) and methyl (E)-3-(methoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate (1.5 mmol) in methanol (10 mL) wasstirred under reflux for 5-10 h. When TLC showed the completionof the reaction, the solution was cooled to room temperature. Theprecipitate was filtered off to give a crude product, which wasrecrystallized from methanol to provide the target compounds.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (E)-Methyl 3-(methoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate, its application will become more common.

Reference:
Article; Qin, Mingze; Tian, Ye; Sun, Xiaoqing; Yu, Simiao; Xia, Juanjuan; Gong, Ping; Zhang, Haotian; Zhao, Yanfang; European Journal of Medicinal Chemistry; vol. 139; (2017); p. 492 – 502;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 88150-75-8, name is Ethyl 4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate, 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 88150-75-8, Formula: C16H17NO6

To a solution of ethyl 4-(2-phthalimidoethoxy)acetoacetate in toluene was added 3000 ml of isopropyl alcohol, 564 g of 2-chlorobenzaldehyde was added with stirring, 17 5g acetic acid, 24.8g piperidine; 20 ~ 30 C, stirring 9 ~ 10h, adding 589g beta-aminocrotonic acid methyl ester, heating to 55 ~ 58 C, and stirring at 55 ~ 58 C reaction, stirring 7h sampling, TLC plate to confirm the end of the reaction, cooling to below 25 C, adding 3200ml acetic acid; then seeded to 0 ~ 5 C, the same temperature for 5h, crystallization; filtration crystallization, with 800ml isopropyl alcohol washing, the wash was run twice (400 ml each) and dried under reduced pressure to give 1611 g of phthaloyl amlodipine in a yield of 76.1%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate, and friends who are interested can also refer to it.

Reference:
Patent; Qianhui Pharmaceutical (Anhui) Co., Ltd.; Yang Huilai; Mao Jie; Sun Xuexi; (7 pag.)CN106749187; (2017); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 446292-07-5,Some common heterocyclic compound, 446292-07-5, name is (R)-2-(2-Hydroxy-3-((4-(3-oxomorpholino)phenyl)amino)propyl)isoindoline-1,3-dione, molecular formula is C21H21N3O5, 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 1 : Preparation of 2-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-l,3-oxazolidin- 5-yl}methyl)-lH-isoindol-l,3(2H)-dione, the compound of formula I(2R)-2-Hydro y-3-[4-(3-oxo-4-mophiholinyl)phenyl]amino-propyl-lH-isoindol-l ,3(2H)- dione (10.0 g; 25 mmol), the compound of formula III, containing 1.0 % of the (2S)-isomer was charged into a flask and tetrahydrofuran (200 ml) was added. NN-carbonyldiimidazole (4.1 g; 25 mmol) was added to the stirred mixture. The mixture was heated up to boil and refluxed for 5 hours.The white suspension was cooled to the temperature of 20C, stirred for 1.5 hours, aspirated and washed with tetrahydrofuran (50 ml). The product was poured into a flask with 2- methoxyethanol (175 ml). The mixture was heated up to boil and stirred until dissolution. Active carbon (0.5 g) was added to the solution and filtered off while hot after 10 minutes and washed with 2-methoxyethanol (10 ml). The solution was cooled to the laboratory temperature and stirred for 1 hour. The resulting crystals were aspirated and washed with methanol (100 ml). The aspirated product was dried in a vacuum drier at a temperature up to 60C. 9 g (85 % of theory) of 2-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-l ,3-oxazolidin-5-yl} methyl)- lH-isoindol- l ,3(2H)-dione with the isomeric purity of 99.98% were obtained, HPLC purity 99.7%, m. p. = 221 – 223 C. The polymorphous structure of the compound (I) was also characterized with the X-ray powder diffraction (Fig. 1) with the characteristic 2 theta angles 4.63; 12.00; 13.9; 15.3; 15.87 and 24.55.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (R)-2-(2-Hydroxy-3-((4-(3-oxomorpholino)phenyl)amino)propyl)isoindoline-1,3-dione, its application will become more common.

Reference:
Patent; FARMAK, A.S.; URBASEK, Miroslav; HRADIL, Pavel; GREPL, Martin; FIALOVA, Petra; OREMUS, Vladimir; SLEZAR, Petr; WO2012/41263; (2012); 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. 35197-64-9, name is 2-Bromo-4-(1,3-dioxoisoindolin-2-yl)butanoic acid, A new synthetic method of this compound is introduced below., Application In Synthesis of 2-Bromo-4-(1,3-dioxoisoindolin-2-yl)butanoic acid

General procedure: In this work, previously reported N-benzyl-2-bromo-4-(1,3-dioxoisoindolin-2-yl)butanamide derivatives (25a-e) [44] were obtained by activating the carboxylic acid group of 24 (1 eqv) by using n-propanephosphonic acid anhydride (T3P, 50% in EtOAc, 1 eqv). The reaction was carried out under argon atmosphere for 2hat 0C in dry methylene chloride. Then, distilled triethylamine (1.2 eqv) and the appropriate N-benzylamine (1.1 eqv) were added to the reaction mixture [57]. The reaction was continued at room temperature for 12h. The products were purified by column chromatography over silica gel (DCM/acetone=9:1) to yield 25a-e as a white solid.

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; ?mudzki, Pawe?; Fija?kowski, ?ukasz; Furga?a, Anna; Gryz?o, Beata; Hoefner, Georg C.; Kulig, Katarzyna; Malawska, Barbara; Malawska, Katarzyna; Nowaczyk, Alicja; Podkowa, Adrian; Rapacz, Anna; Sa?at, Kinga; Wanner, Klaus T.; Zar?ba, Paula; European Journal of Medicinal Chemistry; vol. 188; (2020);,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 356068-93-4, A common heterocyclic compound, 356068-93-4, name is (Z)-5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid, molecular formula is C16H13FN2O3, 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 stirred solution of compound 109 (500 mg, 1.67 mmol) in DMF (40 mL) at room temperature was added etaOBt (337.8 mg, 2.5 mmol), triethylamine (0.94 mL, 6.68 mmol), ECDI etaC1 (477.8 mg, 2.5 mmol) and methyl 8- aminooctanoate hydrochloride (385.3 mg, 1.84 mmol) successively. The mixture was stirred for 24 h at room temperature and diluted with water (20 mL), brine (20 mL) and saturated sodium bicarbonate solution (20 mL). The peta of solution was adjusted to 11-12 with IO N NaOH. The mixture was filtered and the solid was washed with water, dried to obtain a crude product 110-16 as a yellow solid (0.62 g, 86.1%). LCMS: 456 [M+l]+; 1H NMR (DMSO-J6): delta 1.28 (m, 6eta), 1.50 (m, 4H), 2.28 (t, J= 7.35 Hz, 2H), 2.38 ( s, 3H), 2.40 (s,3H), 3.20 (m, 2H), 3.56 (s, 3H), 6.84 (m, 2H), 7.69 (m,3H), 10.87 (s, IH), 13.65 (s, IH).

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; CURIS, INC.; WO2008/33747; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 24566-79-8, 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 24566-79-8 as follows.

2-[6-(4-PHENYL-1-PIPERIDINYL)HEXYL]-1H-ISOINDOLE-1,3(2H)-DIONE: To the 500 ml RB-flask was added 4-phenylpiperidine hydrochloride (5 g, 25 mmol), N-(6-bromohexyl)phthalimide (15.5 g, 50 mmol), N,N-diisopropylethylamine (21.8 ml, 125 mmol), tetrabutylammonium iodide (0.2 g), and dioxane (250 ml) at room temperature. The reaction mixture was stirred at 100 C. for 72 h. The solvent was removed in vacuo and the crude product was purified by flash chromatography (98:2=Chloroform: 2N ammonia in methanol) to afford 7.67 g of the desired product (77% yield): 1H NMR (400 MHz, CDCl3) delta 7.78-7.79 (m, 2H), 7.74-7.65 (m, 2H), 7.32-7.14 (m, 5H), 3.69 (t, 2H, J=7.35 Hz), 3.06 (d, 2H, J=11.0 Hz), 2.49 (quintet, 1H, J=7.6 Hz), 2.36 (t, 2H, J=7.6 Hz), 2.02 (t, 2H, J=12.5 Hz), 1.82 (br s, 4H), 1.69 (t, 2H, J=6.3 Hz), 1.54 (br s, 2H), 1.37 (br s, 4H); ESMS m/e: 391.3 (M+H)+; Anal. Calc. for C25H30N2O2+0.2H2O: C, 76.19; H, 7.77; N, 7.11. Found: C, 76.14; H, 7.38; N, 7.13.

According to the analysis of related databases, 24566-79-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Salon, John A.; Laz, Thomas M.; Nagorny, Raisa; Wilson, Amy E.; Craig, Douglas A.; US2004/38855; (2004); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 17702-83-9, name is 2-(8-Bromooctyl)isoindoline-1,3-dione, 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 17702-83-9, Recommanded Product: 2-(8-Bromooctyl)isoindoline-1,3-dione

a) Preparation of 8-(cis/trans-2,6-dimethyl)morpholinyloctyl phthalimide 8-Bromooctylphthalimide (9 g; 26.60 mmoles) and 2,6-dimethyl morpholine (cis-trans isomers mix) (9.8 ml; 79.5 mmoles) were dissolved in anhydrous acetonitrile (50 ml). The mixture was allowed to stir at room temperature for 18 hours approx. The reaction was discontinued by solvent evaporation under reduced pressure. The collected residue was purified by chromatography on silica gel (CH2Cl2/MeOH 95:5). The first product isolated (Rf = 0.7) is a light yellow oil (A trans) (2.04 g), the second (Rf = 0.4) is a yellow oil (B cis) (3.4 g). Total yield 54.8percent.

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, 2-(8-Bromooctyl)isoindoline-1,3-dione, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MEDIOLANUM FARMACEUTICI S.P.A.; EP575954; (1993); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem