Author: Jessica.F

Application of 21544-81-0, These common heterocyclic compound, 21544-81-0, name is 4,6-Dimethoxyindoline-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.

A solution of 3,5-dimethoxyaniline (199 g, 1.30 mol) in ether (5.0 L) in a 5 L 3-necked flask was cooled to 0C. HCI gas (227 g) was bubbled through the solution over 45 min. After 45 min at 10C, the mixture was filtered, washed with isopropylacetate (4 L), and dried overnight on high vacuum at 45C to give the hydrochloride (242.3 g, 98%), as a white solid. A mixture of the hydrochloride above (20 g, 0.105 mol) and oxalyl chloride (33 mL) in a 3-necked flask equipped with a reflux condenser was heated for 2 h with stirring (170C external temperature), and the oxalyl chloride was distilled from the reaction mixture. The flask was cooled to 0C and methanol (40 mL) was added. The reaction mixture was heated to reflux for 45 min, filtered while hot, and washed with methanol (80 mL) to give the 4,6-dimethoxyisatin (17.2 g, 79%) as a yellow-green solid. To a heated solution (external temp 70C) of the isatin (162 g, 0.78 mol) in aqueous NaOH (40%, 1.5 L) was added H2O2 (35%, 405 mL) slowly over 2 h. After the addition of each portion of H2O2, the internal reaction temperature (initially 64C) increased (to a maximum temp of 80C). After the addition was complete, the foaming reaction mixture was then stirred for an additional 2 h at 70C, and the mixture was allowed to stir overnight while cooling to RT. The mixture was heated to 70C. Additional H2O2 (75 mL) was added, and the mixture was stirred at 70C for a further 2 h until the reaction was complete. After cooling to 10C (bath temperature), aqueous Na2S2O3 (150 mL, saturated) was added. The mixture was brought to pH 8 with HCI (37%, 1.6 L) and pH 6 with acetic acid (glacial, 75 mL), without allowing the reaction mixture to warm to greater than 40C. Filtration of the reaction mixture and washing with water (4 L) gave the expected amino acid as a tan solid (83.7 g, 55%). To a solution of the amino acid (82.7 g, 0.42 mol) in anhydrous THF (4.2 L) was added EDCI (89.2 g, 0.48 mol), HOBT (65 g, 0.48 rnol), and NMM (51.3 mL), and the mixture was allowed to stir at RT for 3 h. Aqueous NH3 (83 mL, 50%) was added, and the mixture was stirred at RT for 16 h. Water (1.25 L) was added, and the mixture was extracted with DCM (2×250 mL). The combined extracts were then washed with water (2×500 mL). Concentration, formation of a slurry with ether (550 mL), filtration, and drying under high vacuum gave 2-amino-4,6-dimethoxybenzamide (46.7 g,57%) as a brown solid. [0111] 2-Amino-4,6-dimethoxy-benzamide (1.06 g, 5.4 mmol), 3,5-dimethyl- 4-hydroxybenzaldehyde (0.810 g, 5.4 mmol), K2CO3 (0.747 g, 5.4 mmol) and I2 (1.645 g, 6.5 mmol) were mixed in DMF (20 ml_) and the reaction mixture was heated at 80C for 12 h. It was cooled to RT and poured into crushed ice. The solid was collected and purified by column chromatography to give 2-(4-hydroxy- 3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4<3H)-one (0.9 g, 51%) as a white solid. Selected data: MP 291-293C. Statistics shows that 4,6-Dimethoxyindoline-2,3-dione is playing an increasingly important role. we look forward to future research findings about 21544-81-0. Reference:
Patent; Resverlogix Corp.; WO2008/92231; (2008); A1;,
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Synthetic Route of 58083-59-3, The chemical industry reduces the impact on the environment during synthesis 58083-59-3, name is 6-Chloroisoindolin-1-one, I believe this compound will play a more active role in future production and life.

A mixture of 6-chloro-2, 3-dihydro-isoindol-1-one (0.115 g, 0.68 [MMOL)] and 6M hydrochloric acid (8 ml) in dioxan (1 ml) was heated to [110¡ãC] for 18 hours. After cooling to room temperature the solid was filtered off and dried in vacuo to give the title compound (0.0055g, 4 percent) as a beige solid. 1H-NMR (400 MHz, DMSO): [A] = 4.30 (brs, 2H), 7.58 (dd, 1H), 7.76 (dd, 1H), 8.22 (brs, 3H). LRMS [(ELECTROSPRAY)] : m/z [MH+] 186. Microanalysis : Found: C, 43.13 ; H, 4.05 ; N, 6. 18. [C8H8N02CI.] HCI requires C, 43.26 ; H, 4.08 ; N, 6. [31percent.]

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, 6-Chloroisoindolin-1-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; PFIZER LIMITED; PFIZER INC.; WO2004/14357; (2004); A2;,
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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. 20870-79-5, name is 5-Nitroindolin-2-one, A new synthetic method of this compound is introduced below., HPLC of Formula: C8H6N2O3

Example 43 tert-Butyl 3-(5-nitro-2-oxoindolin-3-ylidene)pyrrolidine-1-carboxylate (2) A solution of compound 1 (1.0 g, 5.613 mmol), N-Boc-3-pyrrolidinone (1.039 mL, 5.613 mmol) in 7 N NH3 in methanol (10 mL) was refluxed for 2 h. The reaction was brought to room temperature, filtered, washed with methanol (2*5 mL) and dried under vacuum to obtain compound 2 as a solid (1.88 g, 97%). 1H NMR (DMSO-d6) delta 11.29 (s, 1H), 8.19 (dd, 1H, J=2.1, 8.7 Hz), 8.14 (d, 1H, J=1.8 Hz), 7.05 (d, 1H, J=8.4 Hz), 4.56 (s, 2H), 3.61 (t, 2H, J=7.2 Hz), 3.36-3.30 (m, 2H, merged with DMSO peak), 1.44 (s, 9H); ESI-MS (m/z, %): 368 (M+Na, 23), 272 (48), 246 (MH+-Boc, 100).

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; MADDAFORD, Shawn; RAMNAUTH, Jailall; RAKHIT, Suman; PATMAN, Joanne; ANNEDI, Subhash C.; ANDREWS, John; DOVE, Peter; SILVERMAN, Sarah; Renton, Paul; US2008/234237; (2008); A1;,
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Related Products of 101207-45-8, These common heterocyclic compound, 101207-45-8, name is 2-(4-Methylbenzyl)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.

A mixture of 243 2-(4-methylbenzyl)isoindoline-1,3-dione (1 g, 3.8 mmol) and 24 hydrazine hydrate (752 mg, 15 mmol, 730 muL) in 113 MeOH (10 mL) was stirred at 20 C. for 3 hours. The mixture was concentrated in vacuo. The residue was purified by silica gel chromatography (dichloromethane:methanol (with 5% 245 ammonia in 55 water)=0:1 to 5:1) to give 246 p-tolylmethanamine (160 mg).

Statistics shows that 2-(4-Methylbenzyl)isoindoline-1,3-dione is playing an increasingly important role. we look forward to future research findings about 101207-45-8.

Reference:
Patent; H. Lundbeck A/S; Juhl, Karsten; Jessing, Mikkel; Langgard, Morten; Vital, Paulo Jorge Vieira; Kehler, Jan; Rasmussen, Lars Kyhn; Clementson, Carl Martin Sebastian; Marigo, Mauro; (154 pag.)US2019/194189; (2019); A1;,
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Some common heterocyclic compound, 3485-84-5, name is N-Vinylphthalimide, molecular formula is C10H7NO2, 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. Computed Properties of C10H7NO2

Using N-vinylphthalimide and diphenylphosphine oxide as raw materials, the reaction steps are as follows:(1) Add N-vinylphthalimide (0.069 g, 0.4 mmol) to the reaction flask, diphenylphosphine oxide (0.081 g, 0.4 mmol),tert-butyl nitrite (0.041 g, 0.4 mmol), silver nitrate (0.07g, 0.04 mmol), ethanol (2.5mL), 30C reaction;(2) TLC tracks the reaction until complete;(3) The crude product obtained after completion of the reaction was separated by column chromatography (ethyl acetate:petroleum ether=1:1) to give the target product (yield 71%)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3485-84-5, its application will become more common.

Reference:
Patent; Jiangsu Qiangsheng Function Chemical Co., Ltd.; Zou Jianping; Ying Zhiyao; Zhang Peizhi; Tao Zekun; Li Jianan; (19 pag.)CN107573378; (2018); 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 stirred solution of 31 (0.300 g, 0.852 mmol) in THF (10 mL) was added isopropylmagnesium chloride (0.46 mL, 2M solution in THF, 0.920 mmol) at room temperature. After 1 h the reaction mixture was cooled to -20 C and a solution of 3-(1,3-dioxoisoindolin-2-yl)propanal (32) (0.144 g,0.709 mmol) in THF (3 mL) added. The resulting solution was warmed to room temperature, quenched with brine (20 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organics were dried (Na2SO4), filtered and concentrated to give 33 which was used without purification in the next step

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

Reference:
Patent; ACUCELA INC.; WO2008/131368; (2008); A2;,
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Reference of 7699-18-5, A common heterocyclic compound, 7699-18-5, name is 5-Methoxyindolin-2-one, molecular formula is C9H9NO2, 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.

General procedure: The appropriate compound 2 (10 mmol) was dissolved inmethanol (100 mL) and treated with the equivalent of the appropriatealdehyde 1 and piperidine (1 mL). For compounds 39, 41 and42 the yield was much lower (5%), and an improvement (15-20%)was obtained by replacing piperidine with 33% NH4OHThe reaction mixture was refluxed for 5-10 h, except for compounds39-42 which required a longer reflux time (16-24 h; theprogress of the reaction was followed by TLC). The precipitate,formed on cooling, was collected by filtration.Compounds 39e41 were purified by column chromatographywith petroleum ether/acetone as the eluent. Most of the crudeproducts were crystallized from methanol, except 27 (acetone/petroleumether), 34, 43-48, 50-52 (ethanol) and 42, 49 (toluene). Inthe case of compound 10, the two E/Z isomers were isolated byfractional crystallization from methanol.

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; Morigi, Rita; Locatelli, Alessandra; Leoni, Alberto; Rambaldi, Mirella; Bortolozzi, Roberta; Mattiuzzo, Elena; Ronca, Roberto; Maccarinelli, Federica; Hamel, Ernest; Bai, Ruoli; Brancale, Andrea; Viola, Giampietro; European Journal of Medicinal Chemistry; vol. 166; (2019); p. 514 – 530;,
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Reference of 675109-26-9, A common heterocyclic compound, 675109-26-9, name is 6-Bromoisoindolin-1-one, molecular formula is C8H6BrNO, 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.

6-Bromoisoindolin-1-one (636 mg, 3.10 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (930 mg, 3.70 mmol), and Pd(dppf)Cl2 (125 mg, 0.150 mmol) were added to a dry flask and placed under N2. Potassium acetate (900 mg, 9.20 mmol) was weighed directly into the flask. The flask was then evacuated and back filled with N2. Anhydrous N,N-dimethylformamide (DMF) (18 mL) was added and the reaction was heated at 80 C. overnight. The reaction mixture was evaporated to dryness and the resulting material was purified by silica gel chromatography eluting with 0-100% ethyl acetate in hexane to yield 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (493 mg, 62%). ESI-MS m/z calc. 259.1, found 260.1 (M+1)+. Retention time 1.24 minutes.

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; HADIDA RUAH, SARA S.; Miller, Mark; Zhou, Jinglan; Bear, Brian; Grootenhuis, Peter; US2009/143381; (2009); A1;,
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Synthetic Route of 3484-35-3, A common heterocyclic compound, 3484-35-3, name is 5-Methylindolin-2-one, molecular formula is C9H9NO, 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.

General procedure: To a solution of appropriate oxindole (8a-e, 0.3 mmol) in ethanol (3 mL) was addedcorresponding aldehyde (12a-h, 0.32 mmol) and a catalytic amount of piperidine. The reactionmixture was stirred at reflux for 6-12 h (monitored by TLC). After cooling, the precipitate wasfiltered, washed with cold ethanol, and dried in air to furnish pure (Z)-3-(4′-(aminoalkoxy)-3′-methoxybenzylidene)indolin-2-one title compounds of formula (5a-t) as yellow/brown/orangesolids in moderate to excellent yields.

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

Reference:
Article; Senwar, Kishna Ram; Reddy, T. Srinivasa; Thummuri, Dinesh; Sharma, Pankaj; Bharghava, Suresh K.; Naidu; Shankaraiah, Nagula; Bioorganic and Medicinal Chemistry Letters; vol. 26; 16; (2016); p. 4061 – 4069;,
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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. 912999-79-2, name is 5-Chloroisoindoline hydrochloride, A new synthetic method of this compound is introduced below., SDS of cas: 912999-79-2

General procedure: A mixture of Intermediate J (200 mg, 0.66 mmol), Compound 146A, 3-(4-chlorophenyl)pyrrolidine, (143 mg, 0.79 mmol), HATEG (380 mg, 1 mmol), and DIPEA ( 258 mg, 2 mmol) in DMF (5 mL) was stirred at room temperature overnight. The mixture was diluted with EtOAc (50 mL), washed with brine (15 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified with preparative HPLC give Compound 146B. LC-MS (ESI) m/z: 469 [M +H]+.

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; BIOMARIN PHARMACEUTICAL INC.; WANG, Bing; CHAO, Qi; (737 pag.)WO2019/133770; (2019); A2;,
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