Tag: M.W=100-200

Reference of 102-52-3,Some common heterocyclic compound, 102-52-3, name is 1,1,3,3-Tetramethoxypropane, molecular formula is C7H16O4, 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 amixtureof5.0g (19.6 mmol) ofL-tryptophan methylesterand50 mLof methanol,6.0 mL(23.6 mmol) of 1,1,3,3-tetramethoxypropane wasadded. The reaction mixture wasadjusted pH 1-2 withHCl(5N) and stirred at 45 Cfor 48h. The mixture was evaporatedto dryness in vacuo, the residue wasdissolved in a mixture ofwater(30mL) and ethyl acetate (30mL),and the aqueousphasewas extracted with ethyl acetate (30mL×3). The organic phase wascombined, washed successively with 10%Na2CO3andsaturatedNaCl,dried over anhydrousNa2SO4, filtered, andevaporatedto dryness in vacuo. The residue was purified by chromatographyonsilica gel (Chloroform: Methanol, 30:1) toobtain5.4 g of the title compound as pale yellow oilin 88.5% yield.ESI-MS (m/e) 319 [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 1,1,3,3-Tetramethoxypropane, its application will become more common.

Reference:
Article; Wu, Jianhui; Zhao, Ming; Wang, Yuji; Wang, Yaonan; Zhu, Haimei; Zhao, Shurui; Peng, Shiqi; Bioorganic and Medicinal Chemistry Letters; vol. 26; 19; (2016); p. 4631 – 4636;,
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Reference of 14227-17-9, A common heterocyclic compound, 14227-17-9, name is 2,4,6-Trimethoxyaniline, molecular formula is C9H13NO3, 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.

Method C A solution of Intermediate 7 (584 MG,-1. 63 MMOL) in DICHLOROMETHANE (10 mL) was added dropwise at 20C within 10 minutes to a stirred solution of dicyclohexylcarbodiimide (DCC; 370 mg, 1.79 mmol) and pyridine (265 mg, 3.35 MMOL) in dichloromethane (10 mL). The mixture was stirred at 20C for a further 24 hours, followed by addition of DMAP (4.0 mg, 33 PMOL) in one single portion. Subsequently, a solution of Intermediate 1 (358 mg, 1.95 MMOL ; freshly distilled by bulb-to-bulb distillation directly before use) in dichloromethane (5 mL) was added to the stirred mixture at 20C within 10 minutes, and stirring was continued for a further 3 days at 20C (formation of a precipitate). The mixture was then washed with water (2 x 25 mL), the organic layer was separated,. and the aqueous wash solutions were extracted with dichloromethane (2 x 20 mL) in the same order as they had been used for workup. The organic extracts were combined and dried over anhydrous sodium sulphate (remaining solids that did not dissolve in neither phase were filtered off along with the sodium sulphate), the solvent was removed under reduced pressure (rotary evaporator, 800 MBAR/40C), and the residue was dried in vacuo (10 mbar, 20C, 30 minutes) and then purified by column chromatography (column diameter, 3.5 cm; column length, 70 cm; SILICA GEL (15-40, UM, Merck 1.15111), 250 g; eluent, ethyl acetate/n-hexane 55: 45 (V/V)). The relevant fractions (TLC, ethyl acetate/n- hexane 55: 45 (V/V), RF = 0.42) were combined, the solvent was removed under reduced pressure (rotary evaporator; 350 to 150 mbar, 40C), and the residue was dried in vacuo (0.01 mbar, 20C, 1 hour) to give 454 mg of an oil which was dissolved in diethyl ether (8 mL). The resulting solution was then kept undisturbed at 4C for 2 days and AT-20C for a further 4 days (formation of a precipitate). The crystalline solid was isolated by decantation, washed with n- pentane (3 mL), and dried in vacuo (0.01 mbar, 20C, 4 hours) to give 5- [ (3, 5,5, 8, 8-pentamethyl-5, 8-disila-5, 6,7, 8-TETRAHYDRO-2-NAPHTHYL) METHYLL-N-(2, 4, 6- trimethoxyphenyl) furan-2-carboxamide in 37% yield as a colourless crystalline solid (318 mg, 607, UMOL) ; mp 139 C. ANAL. CALCD FOR C28H37NO5SI2 : C, 64. 21; H, 7.12 ; N, 2.67. Found: C, 64. 2; H, 7.1 ; N, 2.7.

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; AMEDIS PHARMACEUTICALS LTD.; WO2004/45625; (2004); A1;,
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Electric Literature of 16452-01-0,Some common heterocyclic compound, 16452-01-0, name is 3-Methoxy-4-methylaniline, molecular formula is C8H11NO, 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.

Reference Intermediate R2 4-methyl-3-(methyloxy)phenol [1376] 4-methyl-3-(methyloxy)aniline (Reference Intermediate R1, 1.86 g) in water (100 mL)/ H2SO4 (30 mL, 563 mmol) at 0 C. a solution of sodium nitrite (1.029 g, 14.91 mmol) in water (10 mL) was slowly added and the reaction mixture was stirred for 30 minutes at 0 C. The reaction mixture was slowly added to a solution of H2SO4 98% (20 mL) in Water (80 mL) pre-heated at 90 C. and stirred at this temperature for 1 h. After cooling the mixture was extracted with Et2O (2×200 mL), the organic layer was dried on sodium sulphate, filtered and evaporated to afford the title compound (1.86 g) as a red/brown oil. [1378] 1H-NMR (400 MHz, DMSO-d6) delta ppm: 9.14 (1H, br.s), 6.87 (1H, d), 6.35 (1H, d), 6.24 (1H, dd), 3.71 (3H, s), 2.01 (3H, s); UPLC_B: 0.63 min, 137 [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-Methoxy-4-methylaniline, its application will become more common.

Reference:
Patent; AUTIFONY THERAPEUTICS LIMITED; Alvaro, Giuseppe; Dambruoso, Paolo; Tommasi, Simona; Decor, Anne; Large, Charles; US2013/267510; (2013); 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. 366-99-4, name is 3-Fluoro-4-methoxyaniline, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C7H8FNO

To cyanuric chloride (28.84 g, 156.0 mmol) dissolved in acetone (200 mL) stirring at approximately 0-5 C, was added a solution of 3-fluoro-p-anisidine (22.16 g, 156.0 mmol) in acetone (200 mL) followed by the addition of NaOH (63 mL, 2.5 N, 156.0 mmol). The reaction mixture was allowed to stir at approximately 0-5 C for about 2 hours. The reaction mixture was then poured over crushed ice and neutralized with 10percent HCI(aq) and 5percent NaOH(aq). The resulting solid was collected by vacuum filtration, washed with water and dried overnight under vacuum. Column chromatography (silica gel, 70: 30 hexane: ethyl acetate) yielded light yellow solid compound 124 (29.6 g, 66percent); mp 134 C ; HPLC: Inertsil ODS-3V C18,40 : 30: 30[KH2PO4(O. 01M, pH 3.2) :CH30H : CH3CN], 264nm, Rt 20.3 min, 97.7 percent purity.

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 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. 7664-66-6, name is 4-Isopropoxyaniline, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C9H13NO

To a mixture of 1-(4-chlorobenzyl)-3-(ethoxycarbonylmethyl)-6-iodoquinazoline-2,4-dion (200 mg, 0.4 mmol), palladium acetate (13.5 mg, 0.06 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (52.2 mg, 0.09 mmol), cesium carbonate (261 mg, 0.8 mmol) and dioxane mL) was added 4-isopropoxyaniline (0.071 ml, 0.48 mmol) under nitrogen atmosphere, and the resulting mixture was heated at reflux for 2 hours. The reaction mixture was poured into a mixture of water (1.00 mL) and 5% aqueous citric acid (10 mL), and the resulting mixture was extracted with ethyl acetate (100 mL). The extract was washed by water (100 mL), dried over anhydrous sodium sulphate, and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane), and the residue was precipitated by hexane to give 1-(4-chlorobenzyl)-3-(ethoxycarbonylmethyl)-6-(4-isopropoxyphenylamino)-quinazoline-2,4-dion (7.7 mg, Yield: 3.7%) as yellow solid. 1H-NMR (delta ppm TMS/CDCl3): 1.28 (3H, t, J=7.2 Hz), 1.33 (6H, d, J=6.0 Hz), 4.24 (2H, q, J=7.2 Hz), 4.74 (1H, m), 4.88 (2H, s), 5.29 (2H, s), 5.61 (1H, s), 6.84 (2H, d, J=8.7 Hz), 6.91 (1H, d, J=9.0 Hz), 7.01 (2H, d, J=8.7 Hz), 7.11 (1H, dd, J=3.0, 9.0 Hz), 7.19 (2H, d, J=8.7 Hz), 7.30 (2H, d, J=8.7 Hz), 7.68 (1H, d, J=2.7 Hz).

According to the analysis of related databases, 7664-66-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SHIONOGI & CO., LTD.; Kai, Hiroyuki; Endoh, Takeshi; Jikihara, Sae; Horiguchi, Tohru; US9212130; (2015); B2;,
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Synthetic Route of 19500-02-8, 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 19500-02-8 as follows.

A. N-tert-butoxycarbonyl-3-methoxy-2-methylaniline. By the method in Example 1, Part A, 25.8 g (188 mmol) of 3-methoxy-2-methylaniline was treated with 41 g (188 mmol) of di-tert-butyl dicarbonate to give by chromatography on silica (eluted with 25percent EtOAc/hexane) 16.4 g (80percent yield) of N-tert-butoxycarbonyl-3-methoxy-2-methylaniline. Analysis: Calc’d for C13 H19 NO3: C, 65.80; H, 8.07; N, 5.90. Found: C, 64.31; H, 7.76; N, 6.58.

According to the analysis of related databases, 19500-02-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Eli Lilly and Company; US5684034; (1997); A;,
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Synthetic Route of 60792-79-2, 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. 60792-79-2 name is 2,2′-Oxybis(ethylamine) dihydrochloride, 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.

Vancomycin (16.0 g, 11.2 mmol, 1.0 eq) was dissolved in [H20] (100 mL) and treated with a solution of 5-amino-3-oxo-pentylamine dihydrochloride salt (10.0 g, [56] mmol, 5 eq) in H2O [(30] mL) and the reaction mixture was stirred at ambient temperature. Triethylamine (22 mL, 160 mmol) was then added, followed by an aqueous solution of formaldehyde (37%, 1. 05 mL, 11.2 mmol) and the reaction mixture was stirred at ambient temperature for one hour. The reaction mixture was diluted with water/acetonitrile (1: 1; 200 mL) and lyophilized. The resulting mixture was dissolved in H2O (50 mL) and purified using large scale HPLC (0-12% gradient over 40 minutes) to provide, after lyophilization, the title compound as a white amorphous powder (7.2 g). HPLC (2-30% gradient): 2.4 min. MS m/z : 1566.9 [M + H]+.

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

Reference:
Patent; THERAVANCE, INC.; WO2003/99858; (2003); A1;,
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Application of 22236-10-8, 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. 22236-10-8, name is 4-(Difluoromethoxy)aniline belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

The nitro ether (149 mmol) was dissolved in ethanol (37.5 mL), diluted with water (25 mL), and was treated with ammonium chloride (84.7 mmol) and iron powder (105 mmol). The reaction mixture was heated at reflux for 30 minutes and the suspension was filtered through Celite. The filter cake was washed with ethanol three times and the combined filtrates were concentrated. The residue was dissolved in water and the pH adjusted to 9-10 with 5 M sodium hydroxide. The aqueous layer was extracted with ethyl acetate (3xlOOmL) and the combined organic layers were dried (magnesium sulfate) and concentrated to a yellow oil. The oil was dissolved in acetic anhydride (23.5 mmol) and the reaction mixture was maintained at rt for 16 h. The reaction mixture was diluted with water (50 mL) and was neutralized with solid sodium bicarbonate. The precipitated solids were isolated by filtration, washed with water, and dried to provide the acetamide in 62% yield as a light yellow solid.

The synthetic route of 4-(Difluoromethoxy)aniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MEMORY PHARMACEUTICALS CORPORATION; WO2005/63767; (2005); A2;,
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Synthetic Route of 767-91-9, These common heterocyclic compound, 767-91-9, name is 2′-Methoxyphenyl acetylene, 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.

Table 5. Copper catalyzed carboxylation of terminal alkynes with CCv Reaction conditions: for LI, CuCl (2.0 mol %), TMEDA, 1.5 mol %; for L12, P(NHC)(NHC-Cu), 5 mol%; alkynes (2.0 mmol), base (2.4 mmol), C02 (1 atm), DMF (4 mL), r.t.. M monocarboxylic acid was obtained. General Procedure for Carboxylation of the Terminal Alkynes (lb as Example); CuCl (4.0 mg, 0.04 mmol, 2.0 mol %), TMEDA (3.5 mg, 0.03 mmol, 1.5 mol %), and K2C03 or Cs2C03 (2.4 mmol) were added to the DMF (4 mL) in the reaction tube (10 mL). C02 and 2 mmol of terminal alkynes (la, 204 mg) were introduced into the reaction mixture under stirring. The reaction mixture was stirred at room temperature (about 24 C) for 16 hours. After completion of the reaction, the reaction mixture was transferred to the potassium carbonate solution (2 N, 5 mL) and the mixture was stirred for 30 mins. The mixture was extracted with dichloromethane (3 >< 5 mL) and the aqueous layer was acidified with concentrated HC1 to PH = 1 , then extracted with diethyl ether (3 chi 5 mL) again. The combined organic layers were dried with anhydrous Na2S04, filtered and the solution was concentrated in vacuum affording pure product. Element analysis calcd (%) for lb [C9H602 (146.0)]: C 73.97, H 4.14; found: C 73.82, H 4.07. Data for 1H and 13C NMR of acids were all conducted in d - DMSO or CDC13 and consistent with the data in reported literatures. The synthetic route of 767-91-9 has been constantly updated, and we look forward to future research findings. Reference:
Patent; AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH; ZHANG, Yugen; YU, Dingyi; WO2011/75087; (2011); A1;,
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Synthetic Route of 41789-95-1, The chemical industry reduces the impact on the environment during synthesis 41789-95-1, name is 1-(3-Methoxyphenyl)-N-methylmethanamine, I believe this compound will play a more active role in future production and life.

General procedure: A solution of bromo heteroaryl carboxylic acid (2mmol), thionyl chloride (4mmol) and DMF (5 drops) in toluene (10mL) was refluxed at 110C for 4h. The reaction mixture was cooled to room temperature and the solvent and the excess of thionyl chloride removed under reduced pressure. To the residue was added at 0C the corresponding N-methyl amine (2mmol) and Et3N (2mmol) in CH2Cl2 (10mL) under N2 atmosphere. After 30min at 0C, the ice bath was removed and the solution was warmed up and stirred at room temperature overnight. The reaction mixture was extracted twice with CH2Cl2 (2×15mL) and the organic layer dried over MgSO4, filtered and the solution was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using hexanes and EtOAc as eluant or by trituration in a mixture of diethyl ether/petroleum ether to afford the desired compound.

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, 1-(3-Methoxyphenyl)-N-methylmethanamine, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Perspicace, Enrico; Cozzoli, Liliana; Gargano, Emanuele M.; Hanke, Nina; Carotti, Angelo; Hartmann, Rolf W.; Marchais-Oberwinkler, Sandrine; European Journal of Medicinal Chemistry; vol. 83; (2014); p. 317 – 337;,
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