Month: May 2021

Reference of 3484-35-3,Some common heterocyclic compound, 3484-35-3, name is 5-Methylindolin-2-one, molecular formula is C9H9NO, 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: To a one-neck round-bottom flask equipped with magnetic stirringwas added 6-chloro-2-indolinone (2a, 1.00 g, 6.0 mmol),vinamidinium salt 324 (2.02 g, 12.0 mmol), Et3N (1.82 g, 18.0mmol), and DMF (10 mL). The mixture was stirred for 20 h atr.t., after the reaction was complete (monitored by TLC,EtOAc/MeOH = 20:1), 30 mL EtOAc and 30 mL water was added,then the aqueous layer was extracted with 30 mL EtOAc. Thecombined EtOAc layer was washed with sat. NaCl solution (15mL) and water (15 mL) then dried over Na2SO4. After filteringthe desiccant, the solvent was concentrated under vacuum to avolume of about 5 mL. The mixture was titrated with 15 mL nhexaneto give a yellow precipitant, the solid was filtered, anddried under vacuum to give 4a (1.34 g, yield 88%), a yellowpowder, which was used in the next step without further purification;mp > 250 C.

The synthetic route of 3484-35-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Tian, Shaixiao; Mao, Yu; Jiang, Yongjun; Xu, Guangyu; Synlett; vol. 29; 7; (2018); p. 949 – 953;,
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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. 769965-95-9, name is 5′-Fluorospiro[cyclopropane-1,3′-indolin]-2′-one, A new synthetic method of this compound is introduced below., SDS of cas: 769965-95-9

Example 2.5Trans-2-chloro-N-{-4-((5′-fluoro-2′-oxospiro[cyclopropane-1 ,3′-indoline]-1 yl)methyl)cyctohexyl}-5-(trifluoromethyl)benzamide 5′-Fluorospiro[cyclopropane-1 ,3′-indolin]-2′-one (Intermediate H) {67 mg, 0.378 mmol) in dry D F (3 ml) was treated with NaH {60% in mineral oil) (15.12 mg, 0.378 mmol) under N2 and the contents left stirring for ~10 mins. After this time, trans- methanesulfonic acid 4-{2-chloro-5-trifluoromethyl-benzoylamino)-cyclohexyl methyl ester (Intermediate C) (105 mg, 0.253 mmol) was added and the solution heated to 70C for 2.5 h. After cooling to RT overnight, the mixture was diluted with EtOAc/H20 (40 ml) and transferred to a separating funnel. The organic layer was separated and washed with brine, dried (MgS04), and concentrated in vacuo to give a light brown oil. The crude oil was chromatographed on silica eluting with a gradient of 0%-30% EtOAc/iso-hexane follwed by an isocratic gradient of 30% EtOAc/iso-hexane to afford the title compound as a white solid; LC-MS Rt= 1.36 mins; [M+H]+ 495.3; Method = 2minl_C_30_v002. 1H NMR (400 MHz, CDCI3). delta 7.90 (1H, s), 7.55 (1 H, d), 7.50 (1H, d), 6.95 (1H, m), 6.80 (1 H, m), 6.60 (1H, m), 5.95 (1 H, d), 4.0 (1H, m), 3.65 (2H, d), 2.20 (2H, m), 1.85 (5H, m), 1.55 (2H, m), 1.25 (4H, m).

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; ATKINSON Benjamin; BEATTIE David; CULSHAW Andrew James; DEVEREUX Nicholas James; MCKENNA Jeffrey; DALE James; WO2011/92293; (2011); A1;,
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Electric Literature of 1504-06-9,Some common heterocyclic compound, 1504-06-9, name is 3-Methyloxindole, molecular formula is C9H9NO, 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 2: Preparation of 3-methyl-3-(pyrimidin-5-ylmethyl)-l,3-dihydro-2H-indol-2-onePyrimidin-5-ylmethanol (510 mg, 4.63 mmol) in tetrahydrofuran (8 mL) at room temperature was treated with sodium hydride (185 mg, 4.63 mmol) and stirred for 5 minutes, p-Toluenesulfonyl chloride (883 mg, 4.63 mmol) was added, and the resulting mixture stirred for one hour to form pyrimidin-5-ylmethyl 4-methylbenzenesulfonate. In a separate flask 3- methyloxindole (682 mg, 4.63 mmol) and JV,iV-dimethylethylenediamine (1.538 mL, 10.19 mmol) in tetrahydrofuran (16 mL) were cooled to -78 0C and treated dropwise with n-butyllithium (2.5M in hexanes, 4.08 mL, 10.2 mmol). The mixture was allowed to warm to 0 0C and stirred for 15 minutes. The mixture was recooled to -78 C. To this mixture was added the tetrahydrofuran solution of pyrimidin-5-ylmethyl 4-methylbenzenesulfonate via cannula; the resulting reaction mixture was allowed to warm to room temperature and was stirred for 18 hours. Water (50 mL) was added, and the mixture extracted with ethyl acetate (2 x 50 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel Biotage 25S, eluting with 0-100% ethyl acetate/hexane to afford 3-methyl-3-(pyrimidin-5-ylmethyl)-l,3-dihydro-2H- indol-2-one as a white solid.1H NMR (CDCl3): delta 8.97 (s, 1 H), 8.29 (s, 2 H), 7.88 (br s, 1 H), 7.25 (d, 1 H, J = 7.3 Hz), 7.20 (m, 1 H), 7.1 1 (m, 1 H), 6.74 (d, 1 H, J = 7.8 Hz), 3.20 (d, 1 H, J – 13.5 Hz), 3.0 (d, 1 H, J – 13.5 Hz), 1.57 (s, 3H) MS: m/e 240.19 (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 3-Methyloxindole, its application will become more common.

Reference:
Patent; MERCK & CO., INC.; WO2009/45386; (2009); A1;,
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897957-06-1, name is 6-Bromo-1-methylindolin-2-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. Computed Properties of C9H8BrNO

Step 3: Synthesis of Intermediate R7 [0295] To I-4.2 (32.0 g, 142 mmol) in anhydrous dioxane (400 mL) is added R3 (54.4 g, 241 mmol) and potassium acetate (41.6 g, 424 mmol). The mixture is purged with Argon, [1,1?-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) as a comple× with dichloromethane (11.2 g, 14 mmol) is added and the mixture is heated to 90 C. for 2 h. The reaction mixture is diluted with ethyl acetate and water, the organic layer is washed with water, dried over MgSO4 and concentrated. The residue is purified via flash chromatography (cyclohexane/EA=70:30). Yield 72%, m/z 274 [M+H]+, rt 0.67 min, LC-MS Method V011_S01

The synthetic route of 897957-06-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; ANDERSKEWITZ, Ralf; GRUNDL, Marc; MORSCHHAEUSER, Gerd; OOST, Thorsten; PAUTSCH, Alexander; US2014/275114; (2014); A1;,
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Reference of 5181-35-1, 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 5181-35-1 as follows.

To a solution of 2-(2-bromoethoxy)isoindoline- l,3-dione (20 g, 7.4 mmol prepared according to the procedure described in step 1 of preparation 10) and 5-methyl- lH-tetrazole (6.22 g, 7.4 mmol) in dimethylformamide (100 ml) was added cesium carbonate (24.13 g, 7.4 mmol) in a lot wise under stirring at 25-30 C. After 16 hours, completion of the reaction was confirmed by performing the thin layer chromatography using mixture of chloroform and methanol as solvent. The resulted reaction mixture was filtered and the filtrate was slowly poured into chilled water (700 ml) under stirring. After 30 minutes of stirring, the reaction mixture was extracted with ethyl acetate (200 ml and 100 ml). The combined organic layer was washed with brine (100 ml). The organic layer was dried on sodium sulfate and concentrated on rota vapour to provide 18 g of the crude product. The two regio isomers were separated by using column chromatography using mixture of acetone and hexane as an eluent. The upper spot isolated at 15-25% concentration of acetone in hexane yielded 7.0 g of non-polar isomer 2-[2-(5-methyl-2H-tetrazol-2-yl)ethoxy]-lH-isoindole-l,3(2H)-dione. The lower spot isolated at 25-40% concentration of acetone in hexane yielded 3.8 g of polar isomer 2-[2-(5-methyl-lH-tetrazol-l-yl)ethoxy]-lH-isoindole-l,3(2H)-dione. (10.8 g, 53 % yield). Analysis: Mass: 274.2 (M+l); for Molecular weight: 273 and Molecular formula: C12H11N5O3.

According to the analysis of related databases, 5181-35-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; WOCKHARDT LIMITED; TADIPARTHI, Ravikumar; PATIL, Vijaykumar Jagdishwar; DEKHANE, Deepak; SHAIKH, Mohammad Usman; BIRAJDAR, Satish; DOND, Bharat; PATEL, Mahesh Vithalbhai; (100 pag.)WO2017/81615; (2017); A1;,
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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. 552330-86-6, name is 5-Bromoisoindolin-1-one, A new synthetic method of this compound is introduced below., Recommanded Product: 552330-86-6

5-Bromoisoindolin-1-one (10 g, 47.16 mmol) and sodium ethanethiolate (9.92 g, 117.90mmol) were mixed together in DMF (100 mL) and the reaction heated to 100 C for 20mm. The reaction was cooled to rt, poured into water (100 mL) and the product extractedwith EtOAc (3 x 200 mL). The combined organic extracts were washed with brine (4 x 50mL). LCMS indicated product in the aqueous washings, and consequently they werecombined and extracted with EtOAc (4 x 50 mL). The organic extracts were combined, dried using a phase separator cartridge and concentrated in vacuo. The solid obtained was dried under high vacuum overnight. 5-(Ethylthio)isoindolin-1-one (8.68 g, 95%) was obtained as a yellow solid. The material was used in the next step without furtherpurification.LC/MS: m/zrr 194 [M+H]. ?H NMR (500 MHz, DMSO-d6) i5 1.27 (t, 3H), 3.06 (q, 2H), 4.33 (s, 2H), 7.36 (dd, 1H), 7.47 – 7.48 (m, 1H), 7.57 (d, 1H), 8.45 (s, 1H).

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; ASTRAZENECA AB; LEVER, Sarah; NARJES, Frank; OLSSON, Roine, Ingemar; VON BERG, Stefan; (124 pag.)WO2018/229155; (2018); A1;,
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These common heterocyclic compound, 3339-73-9, name is 3-(1,3-Dioxoisoindolin-2-yl)propanoic acid, 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 3-(1,3-Dioxoisoindolin-2-yl)propanoic acid

Step-1: 3-(1,3-dioxoisoindolin-2-yl)-N’-(2-methoxyacetyl)propanehydrazide Oxalyl chloride (27.47 g, 0.216 mol) was added slowly to an ice-cooled solution of 3-(1,3-dioxoisoindolin-2-yl)propanoic acid (15.80 g, 0.072 mol) in DCM (250 mL) followed by catalytic DMF (0.5 mL). The reaction mixture was stirred at room temperature for 1 h and volatiles were removed completely under vacuum to obtain the intermediate acid chloride as a yellow solid. A solution of 2-methoxyacetohydrazide (2, 9.01 g, 0.086 mol) in DCM (50 mL) was added to a solution of this acid chloride in DCM (200 mL) at 0 C. followed by triethylamine (60.5 g, 0.597 mol). The resultant reaction mixture was stirred at room temperature for 1 h. The resulting yellow suspension was quenched onto crushed ice (200 mL). Separated organic layer was washed with water (2×200 mL), brine (150 mL) and concentrated under vacuum to afford crude product (5 g). The aqueous layer which also contains desired product was concentrated under reduced pressure to afford a solid residue. The crude residue was dried and extracted sequentially with THF (1000 mL), acetone (300 mL) and acetonitrile (400 mL). The combined organic layer was concentrated to obtain yellow semisolid (37 g) which was combined with solid residue (5 g) from organic layer and was used in the next reaction without purification. LC-MS [M+H]+ 306.1 m/z.

The synthetic route of 3-(1,3-Dioxoisoindolin-2-yl)propanoic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PROTEOSTASIS TEHRAPEUTICS, INC.; Bastos, Cecilia M.; Munoz, Benito; Tait, Bradley; (48 pag.)US2017/1993; (2017); A1;,
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Related Products of 356068-93-4,Some 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, 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 10: Preparation of (Z)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)- TV- (8-(hydroxylamino)-8-oxooctyl)-2,4-dimethyl-lH-pyrrole-3- Carboxamide (Compound 16)Step 10a. (Z)-Methyl 8-(5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl – IH- pyrrole-3-carboxamido)octanoate (Compound 110-16)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 10 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+lf; 1H NMR (DMSO-^6): delta 1.28 (m, 6H), 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).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (Z)-5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid, its application will become more common.

Reference:
Patent; CURIS, INC.; WO2008/33743; (2008); A1;,
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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. 132898-96-5, name is 2,3-Dioxoindoline-5-sulfonyl chloride belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Application In Synthesis of 2,3-Dioxoindoline-5-sulfonyl chloride

(S)-5-(2-(4-Fluorophenoxymethyl)-pyrrolidine-1-sulfonyl)isatin (compound 20b). To a stirred solution of 19b (0.15 g, 0.5 mmol) in dry DCM (4 mL) cooled in an ice bath was added TFA (0.6 mL, 10 mmol). After 1 h bulk solvent was removed in vacuo and the residue remaining taken up in dry DCM (8 mL) and cooled in an ice bath. Dry triethylamine (1.5 mL) was then added followed by 5-chlorosulfonylisatin8 (0.16 g, 0.65 mmol) in dry THF (4 mL) and the solution was then stirred. After 19 h bulk solvent was removed in vacuo and redissolved in DCM (10 mL), washed with water (2*10 mL), then brine (1*10 mL) and dried over Na2SO4. Chromatography (hexanes/ethyl acetate) gave the desired product as an orange solid (104 mg, 51%). Mp: 205-207 C. HRMS (ESI)=405.0941 (M+H)+. Calcd. for C19H18FN2O5S 405.0920. 1H NMR (600 MHz, CDCl3) delta 8.10 (s, 1H), 8.08 (dd, J=8.4 Hz, J=1.8 Hz, 1H), 8.00 (br, 1H), 7.00 (d, J=7.8 Hz, 1H), 6.99-6.95 (m, 2H), 6.83-6.81 (m, 2H), 4.17 (dd, J=9.6 Hz, J=3.6 Hz, 1H), 3.98-3.95 (m, 1H), 3.91 (dd, J=9 Hz, J=7.8 Hz, 1H), 3.54-3.50 (m, 1H), 3.24-3.19 (m, 1H), 2.10-1.99 (m, 2H), 1.87-1.77 (m, 2H). TLC (UV254) Rf=0.27 (2:1 ethyl acetate/hexanes). HPLC tR=7.83

The synthetic route of 132898-96-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Imperial Innovations Limited; Hammersmith Imanet Limited; US2011/195024; (2011); A1;,
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Reference 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.

5-Nitro-2-oxindole (6.3 g) was hydrogenated in methanol over 10% palladium on carbon to give 3.0 g (60% yield) of 5-amino-2-oxindole as a white solid.

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:
Patent; SUGEN, Inc.; US2002/183364; (2002); A1;,
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