Author: Jessica.F

Some common heterocyclic compound, 658-89-9, name is 4-(Trifluoromethoxy)benzene-1,2-diamine, molecular formula is C7H7F3N2O, 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. Quality Control of 4-(Trifluoromethoxy)benzene-1,2-diamine

Intermediate 67: Mixture of (trans)-N-{2-amino-4-r(trifluoromethyl)oxylphenyl)-2-oxo-3-(3- pyridinyl)-1-oxa-3-azaspiror4.5ldecane-8-carboxamide and (trans)-N-{2-amino-5- [(trifluoromethvDoxyiphenvD^-oxo-S-O-pyridinvD-i-oxa-S-azaspiroK.deltaidecane-delta- carboxamide; Lithium (trans)-2-oxo-3-(3-pyridinyl)-1-oxa-3-azaspiro[4.5]decane-8-carboxylate (Intermediate 66, 75 mg, 0.251 mmol) and EDC (77 mg, 0.401 mmol) were suspended in pyridine (2 ml) and stirred for 30 min. 4-[(trifluoromethyl)oxy]-1 ,2-benzenediamine (Intermediate 32, 72.2 mg, 0.376 mmol) was then added and the resulting dark solution was stirred overnight at r.t. Solvent was removed under vacuum, taken up with DCM (20 ml) and washed with saturated NaHCO3 solution (2X5 ml). The organic phase was concentrated under vacuum to afford a crude oil. The crude was purified by flash chromatography on Biotage SP1 (25+M column, NH cartridge) eluting in gradient with CyclohexaneEtOAc. The title compound was eluted with 100% EtOAc and recovered as colourless solid (60 mg) as mixture of regioisomers with unknown ratio. 1 H-NMR (400 MHz, CD3OD): delta 8.88 (br s, 2H), 8.34-8.32 (m, 2H), 8.13 (dq, 2H), 7.50-7.45 (m, 2H), 7.18-7.14 (m, 2H), 6.97-6.95 (m, 1 H), 6.75-6.73 (m, 1 H), 6.58-6.53 (m, 2H), 3.74 (s, 4H), 2.68-1.68 (m, 18 H); UPLC-MS: 0.60 min, mz 226 [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 658-89-9, its application will become more common.

Reference:
Patent; GLAXO GROUP LIMITED; WO2008/129007; (2008); A1;,
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Reference of 366-99-4, These common heterocyclic compound, 366-99-4, name is 3-Fluoro-4-methoxyaniline, 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.

Was added in a 500 mL reaction flask3-fluoro-4-methoxyaniline(30 g, 0.21 mol) and dichloromethane(100 mL).The ice bath was cooled to below 5 ° C,Acetic anhydride was slowly added dropwise(22 mL, 0.23 mol),The temperature of the reaction solution was controlled at 30 ° C or lower,About 1 hour period.Remove the ice bath,After stirring at room temperature for 5 hours,N-Hexane (300 mL) was added to the reaction solution,A large number of solid precipitation.After stirring for 1 hour,The filter cake was washed with n-hexane,30 degrees vacuum drying,To give the title compound (whiteColor solid powder, 28 g, 72percent).

The synthetic route of 366-99-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Zhang, Ruihao; (36 pag.)CN105949178; (2016); 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. 162705-07-9, name is (Z)-2-Methoxy-5-(3,4,5-trimethoxystyryl)aniline, A new synthetic method of this compound is introduced below., HPLC of Formula: C18H21NO4

In a three-necked flask equipped with a stirrerDOTA (20 g, 0.05 mol),Thionyl chloride (200 ml)Stirring, heating reflux 4h,After cooling, the dichlorosulfone liquid was distilled off under reduced pressure,Then, 100 ml of dry THF was added, the solvent was distilled off under reduced pressure,To give solid acid chloride.The resulting solid acid chloride was dissolved in 250 ml of dry dichloromethane,Adding 20 ml of diisopropylethylamine,Stir,Ice bath to join(Z)-1- (3,4,5-trimethoxyphenyl) -2- (3-hydroxy-4-methoxyphenyl) ethylene (4 g, 0.0125 mol), the ice bath was removed and the temperature was gradually raised to 30 C. 3h, TLC tracking.After the reaction, add ice water 100ml, stirring 30min, vacuum distillation of organic solvents. In the aqueous phase with concentrated hydrochloric acid to adjust the pH to 2, a solid precipitation, filtration to obtain a white solid,Recrystallization from an ethanol-water solution gave 22.8 g of the desired product in 65% yield.

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; Zhejiang Dade Pharmaceutical Group Co., Ltd.; Wang Jianping; Wang Jianguo; (23 pag.)CN104447598; (2017); B;,
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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. 10541-78-3, name is 2-Methoxy-N-methylaniline, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 2-Methoxy-N-methylaniline

General procedure: The N-methyl aniline intermediates were prepared according to the method in the literature. To a solution of sodium 3,4-dioxo-3,4-dihydronaphthalene-1-sulfonate (2) (130 mg, 0.5 mmol) in water (15 mL), N-methyl aniline intermediate (0.55 mmol) was added. The reaction mixture was stirred at room temperature for 3 to 20 h (TLC monitoring). For the preparation of compounds 3, the solvent was removed in vacuum, and the residue was purified by column chromatography to give the target products. For the preparation of compounds 4, the precipitate produced was filtered, and the residue was crystallized from EtOH to give compounds 4 as red solids.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 10541-78-3.

Reference:
Article; Yang, Honghao; An, Baijiao; Li, Xingshu; Zeng, Wei; Bioorganic and Medicinal Chemistry Letters; vol. 28; 18; (2018); p. 3057 – 3063;,
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Reference of 366-99-4, These common heterocyclic compound, 366-99-4, name is 3-Fluoro-4-methoxyaniline, 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 cyanuric chloride (0.180 g,1 mmol) in 1,4-dioxane (1 mL) at about- 10 to-20 C was addedN, N-diisopropylethylamine (DIEA) (0.19 mL,lmmol) in CH3CN (1 mL) and3-fluoro-p-anisidine (0.14 g, 1 mmol) inCH3CN(1 mL) and stirred for about1 hour. The reaction mixture was then stirred at room temperature for about I hour. Then a solution of cycloheptylamine (0.13mL,1 mmol) and DIEA (0.19 mL, 1 mmol) inCH3CN (0.5 mL) was added and the reaction mixture was stirred overnightat rt. Then, N-methyl-4 (methylamino) piperidine (0.15 mL,1 mmol) and DIEA (0.19 mL,1 mmol) inCH3CN (0.5 mL) were added and the reaction mixture was refluxed overnight. The reaction mixture was worked-up using saturated sodium bicarbonate, and brine. The organic layer was separated and dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 90: 9: 1 dichloromethane: methanol:conc. ammonium hydroxide) to give 158 (0.130 g, 28percent) ; TLC (silica gel, 90: 9 : 1,CH2CI2, CH30H, conc.NH40H), Rf 0.26) ;1H NMR (600MHz, CDC13, 55 C)8 7.74 (br s, 1H), 6.94 (br s, 1H), 6.81-6. 84(m, 2H), 4.83 (br resonance, 1H), 4.55 (s,1H), 3.98 (s,1H), 3.82 (s,3H), 2.97 (s, 3H), 2.94 (br d,J=11. 9 Hz, 2H), 2.29 (s, 3H), 2.06-2. 10(m, 2H), 1.93-1. 97(m, 2H), 1.84-1. 90(m, 2H), 1.44-1. 66(m, 12H). Compound 159 was’isolated as a by-product (55 mg) by column chromatography (silica gel, 90: 9: 1 dichloromethane: methanol:conc. ammonium hydroxide); TLC (silica gel, 90: 9: 1,CH2C12, CH30H, conc.NH40H), Rf 0.1) ; HPLC: Inertsil ODS-3V C18, 40: 30: 30 [KH2PO4(0. 01 M, pH 3.2) :CH30H : CH3CN], 264nm, Rt 8.3 min, 93.5percent purity; MS(ESp : m/z 443 (M+H, 100).

Statistics shows that 3-Fluoro-4-methoxyaniline is playing an increasingly important role. we look forward to future research findings about 366-99-4.

Reference:
Patent; REDDY US THERAPEUTICS, INC.; WO2004/26844; (2004); A1;,
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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. 701-56-4, name is 4-Methoxy-N,N-dimethylaniline, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C9H13NO

General procedure: A 25 mL round bottomed flask was charged with N,N-dialkyl-aniline (0.5 mmol), 2-naphthol (0.5 mmol) and acetonitrile (3 mL), followed by 10 mg of Ce-MCM-41 and TBHP (2 equiv.) via syringe. The mixture was heated to 60 C and stirred for 3 h in open air. After completion of the reaction, as judged by TLC, the solution was cooled and the catalyst was removed by filtration. The resulting crude mixture was gently evaporated under reduced pressure and purified by column chromatography using silica gel and a mixture of hexane and ethyl acetate as the eluent.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 701-56-4.

Reference:
Article; Akondi, Adinarayana Murthy; Trivedi, Rajiv; Sreedhar, Bojja; Kantam, Mannepalli Lakshmi; Bhargava, Suresh; Catalysis Today; vol. 198; 1; (2012); p. 35 – 44;,
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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. 103291-07-2, name is 4-Bromo-1-fluoro-2-methoxybenzene, This compound has unique chemical properties. The synthetic route is as follows., Formula: C7H6BrFO

Example 2; 2-(4-Fluoro-3-methoxvphenvlV4,4,5.5-tetramethvl-1.3,2-dioxaborolane; Anhydrous 1,2-dimethoxy ethane (12 mL) was added to 4-bromo-l-fluoro-2- methoxybenzene (1.02 g, 5.0 mmol), tris(dibenzylideneaceton)dipalladium (0) (228 mg, 0.25 mmol), tricyclohexylphosphine (209 mg, 0.75 mmol), potassium acetate (732 mg, 7.5 mmol) and 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-l,3,2-dioxaborolane (1.14 g, 4.5 mmol) and 5 the resulting mixture was irradiated in a microwave at 150 C for 1 h. When cooled to ambient temperature the mixture was filtered and the solvent was evaporated in vacuo to give the crude product: MS (EI) m/z 252 [M+*].

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 103291-07-2.

Reference:
Patent; ASTRAZENECA AB; ASTEX THERAPEUTICS LTD; WO2007/145569; (2007); A1;,
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Application of 148583-65-7, These common heterocyclic compound, 148583-65-7, name is 4-Fluoro-2-isopropoxyaniline, 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.

Example 1 5-Ethyl-N-(4-fluoro-2-isopropoxy^henyl)pyrrolo[3,2-d]pyrimidin^ 2-isopropoxy-4-fluoroaniine (55mg, 0.33mmol), Intermediate 2 (54mg, 0.30mmol), 4M HCi in dioxane (0.1ml) and IPA (2ml) were heated in the microwave at 140C for 20 min. The mixture was concentrated and purified by preparative LCMS to give a white solid (41 mg, 44%); 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.43 (d, J=6.0 Hz, 6 H), 1.61 (t, J=7.3 Hz, 3 H), 4.45 (q, J=7.3 Hz, 2 H), 4.68 (spt, J=6.0 Hz, 1 H), 6.60 (d, J=3.2 Hz, 1 H), 6.69 (dd, J=10.0, 2.7 Hz, 1 H), 6.75 (td, J=8.7, 2.7 Hz, 1 H), 7.24 (d, J=3.2 Hz, 1 H), 7.58 (br. s, 1 H), 8.54 (s, 1 H), 8.75 (dd, J=8.9, 6.2 Hz, 1 H); LC-MS (ESI): (MH+) 315.2

The synthetic route of 148583-65-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MEDICAL RESEARCH COUNCIL TECHNOLOGY; WINTER-HOLT, Jon James; MCIVER, Edward Giles; LEWIS, Stephen; OSBORNE, Joanne; (106 pag.)WO2017/85483; (2017); A1;,
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Some common heterocyclic compound, 36865-41-5, name is 1-Bromo-3-methoxypropane, molecular formula is C4H9BrO, 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. Quality Control of 1-Bromo-3-methoxypropane

To a 50 Ljacket reactor containing 5-bromo-2-methoxy-phenol (1.185 kg, 5.78mo1), 1- bromo-3-methoxy-propane (1.028 kg, 6.52 mol) and acetonitrile (12 L) was added anhydrousK2C03 (1.212 kg, 8.68 mol) in one portion at room temperature. The resulting mixture was heated to 75 C and the agitation was maintained for 16 hours. The reaction mixture was slowly cooled to room temperature, and to the mixture was added water (6 L) and EA (8 L). The organic phase was separated and washed with 5% brine (6 L) again. The organic layer was filtered through a Na2504 pad, and concentrated under reduced pressure to give 1.6 Kg of 4-bromo- 1-methoxy-2-(3-methoxypropoxy)benzene as a light brown solid, which was used directly in thenext step without further purification. The yield was 98 %, the purity was 99.3 %, and MS obsd.(ESIj [(M+H)i: 275.1. ?H NMR (400 MHz, DMSO-d6) oe ppm 1.84 – 2.04 (m, 2 H) 3.25 (s, 3H) 3.33 (s, 1 H) 3.46 (t, J=6.27 Hz, 2 H) 4.01 (t, J=6.27 Hz, 2 H) 5.58 – 9.80 (m, 3 H) 5.58 – 9.80(m, 3 H) 6.92 (d, J=8.53 Hz, 1 H) 7.04 – 7.13 (m, 2 H)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 36865-41-5, its application will become more common.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; DU, Zhengming; WANG, Lin; (43 pag.)WO2017/16960; (2017); A1;,
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These common heterocyclic compound, 36805-97-7, name is 1,1-Di-tert-butoxy-N,N-dimethylmethanamine, 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 1,1-Di-tert-butoxy-N,N-dimethylmethanamine

A stirred suspension of methyl 4-(3,5-dichloro-4-hydroxybenzamido)benzoate (1) (Synthesis 9) (100 mg, 294 mumol) in toluene (2 mL) was heated at 80 C. until homogenous. The resultant solution was treated with 1,1-di-tert-butoxy-N,N-dimethylmethanamine (141 muL, 588 mumol) and the mixture heated at 80 C. for 3 h, and then at RT for 18 h. Additional 1,1-di-tert-butoxy-N,N-dimethylmethanamine (141 muL, 588 mumol) was added and mixture was heated at 80 C. for 5 h. The reaction mixture was cooled to RT and solvent was removed in vacuo. The residue was diluted with water and extracted with Et2O. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was partially purified by silica gel chromatography (12 g, 0-50% EtOAc in isohexane) to afford methyl 4-(4-(tert-butoxy)-3,5-dichlorobenzamido)benzoate (2) (82 mg, 71%). The material was used in the next step without further purification.

The synthetic route of 1,1-Di-tert-butoxy-N,N-dimethylmethanamine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KING’S COLLEGE LONDON; US2012/149737; (2012); A1;,
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