Author: Jessica.F

Some common heterocyclic compound, 618-89-3, name is Methyl 3-bromobenzoate, molecular formula is C8H7BrO2, 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 C8H7BrO2

In a 25 mL round-bottomed flask, toluene (10 mL) was degassed with argon for 20 min. Under a flow of argon, Pd(OAc)2 (0.05 g, 0.23 mmol), BINAP (0.23 g, 0.37 mmol) and Cs2CO3 (2.12 mmol, 6.51 mmol) were added and left to stir for a further 20 min. To the mixture, methyl (3-bromobenzoate) 1 (1.01 g, 4.65 mmol) and aniline 2 (0.51 mL, 5.58 mmol) were added. The reaction was stirred at 120 C and monitored by thin layer chromatography (TLC) for 24 h. Upon completion, the reaction was cooled to room temperature and filtered through Celite, with hexane as the eluent, followed by concentration under reduced pressure. The residue was purified by flash column chromatography on silica eluting with hexane/ethyl acetate (90:10) (Rf 0.23) to afford 0.87 g (82%) of 3 as a pale yellow solid; M.p. 110-112 C (literature M.p. 110-111 C) [40]; 1H NMR (400 MHz/CDCl3)/ppm, delta = 3.90 (s, 3H,-COOCH3), 5.81 (s, 1H, -NH), 6.98 (app. t, 1H, app J = 8 Hz, CHparaC4H4-NH), 7.09 (app. d, 2H, CHparaC2H2metaC2H2ortho-NH), 7.23 (m, 1H, HN-CH-C(COOCH3)-CHCHCH-), 7.29 (m, 3H, C2H2ortho-HN-CH-C(COOCH3)-CHCHCH-), 7.57 (app. d, 1H, HN-CH-C(COOCH3)-CH), 7.72 (m, 1H, HN-CHC(COOCH3)); 13C NMR (100 MHz/CDCl3)/ppm, delta = 52.2, 118.2, 118.4, 121.5, 121.77, 121.80, 129.4, 129.3, 131.4, 142.4, 143.6, 167.1; Found [M+H]+ (C14H14NO2) m/z 228.1019 (Calc. 228.1025); IR (ATR) v/cm-1: 3358, 3030, 1694, 1578, 1294, 744.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 618-89-3, its application will become more common.

Reference:
Article; Higgins, Clare L.; Filip, Sorin V.; Afsar, Ashfaq; Hayes, Wayne; Tetrahedron; vol. 75; 51; (2019);,
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Application of 1000342-11-9, A common heterocyclic compound, 1000342-11-9, name is Methyl 3-amino-5-bromo-2-methylbenzoate, molecular formula is C9H10BrNO2, 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.

Methyl 5-bromo-2-methyl-3-((tetrahydro-2H-pyran-4-yl) amino) benzoate (2) A reactor was charged with methyl 3-amino-5-bromo-2-methylbenzoate (455.8 g, 1.87 mol), 1,2- Dichloroethane (4.56 L), and acetic acid (535 ml, 9.34 mol). To the mixture were added dihydro-2H-pyran-4(3H)-one (280 g, 2.80 mol) and sodium triacetoxyborohydride (594 g, 2.80 mol) maintaining the internal temperature below 40 C. The mixture was stirred at 25 C for 2.5 h and then the reaction was quenched with a solution of sodium hydroxide (448 g, 11.20 mol) in water (5.61 L). After stirring for 20 minutes at ambient temperature, the organic layer was separated and the aqueous layer was extracted with ethyl acetate (3.65 L). The organic layers were combined, washed with brine (1.5 L), and concentrated under vacuum. The residue was treated with ethyl acetate (1.8 L) and heated to 65-70 C. The mixture was stirred at 65-70 C for 15 minutes to give a clear solution and then treated with n-heptane (7.3 L) maintaining the temperature between 60-70 C. Once the heptane was completely added to the solution, the mixture was held at 65-70 C for 15 minutes and then allowed to cool to 18- 22 C over 3 h. The resulting suspension was stirred at 18-22 C for 4 h, cooled to 0-5 C over 1 h, and held at 0-5 C for 2 h. The precipitate was filtered, washed twice with n-heptane (1.4 L), and dried under vacuum to give the title compound (540 g, 88%). The XRPD pattern of this compound is shown in Figure 17.

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; EPIZYME, INC.; EISAI R&D MANAGEMENT CO.LTD.; KUNTZ, Kevin, Wayne; HUANG, Kuan-chun; CHOI, Hyeong, Wook; SANDERS, Kristen; MATHIEU, Steven; CHANDA, Arani; FANG, Frank; WO2013/155317; (2013); A1;,
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Application of 52727-57-8, These common heterocyclic compound, 52727-57-8, name is Methyl 2-amino-5-bromobenzoate, 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 88:Methyl 2-amino-5-[4-(methylsulfonyImethyl)-6-morpholin-4-yl-pyrimidin-2- yljbenzoateA mixture of methyl-2-amino-5-bromobenzoate (250 mg), potassium acetate (320 mg) and bis(pinacolato)diboron (332 mg) in 1,4-dioxane (10 mL) was degassed for 5 minutes. 1,1′- Bis(diphenylphosphino)ferrocenedichloropalladium(II) dichloromethane adduct (54 mg) was added and the reaction was heated to 8O0C for 2.5 hours. 2-Chloro-4-(methylsulfonylmethyl)-6-mophiholin-4-yl-pyrimidine (381 mg), ethanol (0.75 mL), a 2M solution of sodium carbonate (2.7 mL) and additional 1,1′- bis(diphenylphosphino)ferrocenedichloropalladium(II) dichloromethane adduct (54 mg) were added and the heating was continued for a further 3.5 hours. The cooled reaction mixture was loaded on a SCX-2 (10 g), removed with 7N ammonia in methanol and the solution concentrated in vacuo. The residue was chromatographed on silica, eluting with 50% ethyl acetate in DCM, to give the desired material as a yellow solid (82 mg). Mass Spectrum; MH+ 407 NMR Spectrum: 1H NMR (DMSO-d6) 53.22 (3H, s), 3.69 (4H, s), 3.73 (4H, s), 3.84 (3H, s), 4.49 (2H, s), 6.77 (IH, s), 6.87 (IH, d), 7.05 (2H, s), 8.24 (IH, d), 8.79 (IH, s)

The synthetic route of 52727-57-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2007/80382; (2007); A1;,
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Application of 921222-14-2, 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. 921222-14-2 name is Ethyl 2,3-diamino-6-(methylthio)benzoate, 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 solution of 2,3-diamino-6-methylsulfanyl-benzoic acid ethyl ester (150 mg) in acetonitrile (10 mL) are added 2,3-dichlorophenyl isothiocyanate (98 muL). The reaction mixture obtained is stirred 1 hour at RT and N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydro-chloride (EDCI, 166 mg) is added. The mixture obtained is cooled to RT, quenched with H2O and extracted with EtOAc. The organic layers obtained are combined, dried over MgSO4, filtrated and solvent is evaporated to afford the title compound (LC/MS Rt=3.55, [M]+=395.93 and 397.89 and 399.89).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 2,3-diamino-6-(methylthio)benzoate, and friends who are interested can also refer to it.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2007/9774; (2007); 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. 1260092-46-3, name is tert-Butyl 3-(2-aminoethoxy)propanoate, A new synthetic method of this compound is introduced below., name: tert-Butyl 3-(2-aminoethoxy)propanoate

To a solution of fert-butyl 3-(2-aminoethoxy)propanoate (246 mg, 1.302 mmol) in DMF (1.5 ml) at rt was added bis(2,5-dioxopyrrolidin-l-yl) 3,3′-oxydipropanoate (232 mg, 0.651 mmol) and followed DIPEA (0.284 ml, 1.628 mmol). The mixture was allowed to stir at rt over night and concentrated to dryness. To the resulting residure at 0 C was added 1.0 mL neat TFA, and the resulting mixture was allowed to stir at rt overnight. The mixture was concentrated to give the crude product, which was used without further purification. UPLC-MS Method A: TR = 0.7 min, m/z = 393 (z = 1).

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; MERCK SHARP & DOHME CORP.; LIN, Songnian; YAN, Lin; HUO, Pei; PISSARNITSKI, Dmitri; FENG, Danqing; NARGUND, Ravi; MADSEN-DUGGAN, Christina; ZHU, Yuping; KEKEC, Ahmet; WU, Zhicai; (191 pag.)WO2017/205309; (2017); A1;,
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These common heterocyclic compound, 108928-00-3, name is Ethyl 2,4-difluorobenzoate, 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. COA of Formula: C9H8F2O2

2,4-Difluorobenzoic acid ethyl ester (5.33g) was cooled to 0C and treated with concentrated sulfuric acid (3. 5mL) and then fuming nitric acid (3. 5mL). The mixture was stirred for 2 hours at 0C and then partitioned between dichloromethane (2x50mL) and water (25mL). The organic phase was back extracted with water (25mL) and then dried over magnesium sulfate and concentrated in vacuo. This provided the desired compound as a white solid (5. 00g) which was used without further purification.

The synthetic route of Ethyl 2,4-difluorobenzoate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SMITHKLINE BEECHAM P.L.C.; WO2003/87098; (2003); A1;,
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These common heterocyclic compound, 6279-86-3, name is Triethyl methanetricarboxylate, 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 Triethyl methanetricarboxylate

10129] 14.5 parts (62.4 mmol) of triethyl carboxymalonate,11.4 parts (76.4 mmol) of 5-amino-2-benzimidazolinone and0.138 part (0.626 mmol) of 2,6-di-tert-butyl-p-cresol weredissolved in 141 parts (1.93 mol) of N,N-dimethylformamide, and reacted under heating and stirring at 800 C. for 6hours. After the reaction, N,N-dimethylformamide was distilled away under reduced pressure, and 300 parts (16.7 mol) of water was added to the obtained residue. The deposit was filtered to thereby obtain the intermediate (4).

The synthetic route of Triethyl methanetricarboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CANON KABUSHIKI KAISHA; CANON FINETECH INC.; Kubo, Haruko; Ueno, Suzuka; Chizuwa, Junko; Yamamoto, Tomoya; Itabashi, Hitoshi; Terui, Yuhei; Yoshida, Yu; Murai, Yasuaki; Toyoda, Takayuki; (26 pag.)US2016/130233; (2016); 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. 35180-01-9, name is Chloromethyl isopropyl carbonate, A new synthetic method of this compound is introduced below., Formula: C5H9ClO3

Tenofovir (60 g, 0.209 mol) was placed in a 500 ml four-necked flask.250 g of N-methylpyrrolidone, and triethylamine (62.3 g, 0.617 mol) was added with stirring.Additional tetrabutylammonium bromide (40.25 g, 0.125 mol) was added.Warming up to 50 C,At this temperature, chloromethyl isopropyl carbonate (63.5 g, 0.418 mol) was added dropwise.Investment,Keep warm for 5 to 10 hours,After the end of the heat preservation, after extracting twice with n-heptane 250 ml×2, the water was separated into 480 g of purified water, and extracted three times with isopropyl acetate 240 g+120 g+120 g, and the isopropyl acetate solution was combined and washed twice with an aqueous solution of 180 g×2. , concentrated to dryness under reduced pressure at 40 C, 60 g of isopropanol, 40 CConcentrated to dryness under reduced pressure, adding 100 g of isopropanol, heating and dissolving, cooling to -10 to -20 C, adding 0.5 g of seed crystals, keeping for 2-8 hours, suction filtration,The wet product was dried at 40 C under reduced pressure to obtain tenofovir (99.28 g).Yield 91.5%The purity is 98.3%.

The synthetic route of 35180-01-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Zhejiang Jiuzhou Pharmaceutical Co., Ltd.; Ye Meiqi; Xu Jiankang; Wu Hao; Chen Linguo; Ye Kai; (17 pag.)CN104974188; (2019); B;,
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Some common heterocyclic compound, 1215205-50-7, name is Ethyl 1-(4-bromophenyl)cyclopropanecarboxylate, molecular formula is C12H13BrO2, 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. Product Details of 1215205-50-7

l-(4-Bromo-phenyl)-cyclopropanecarboxylic acid ethyl ester (3.6g, 13.4mmol), bis(pinacolato)diboron (3.37g, 16. lmmol), and potassium acetate (2.8g, 29mmol) were combined in 1,4-dioxane (3OmL). The solution was purged with N2 for 10 minutes, and then (l,l’-bis(diphenylphosphino)ferrocene)- dichloropalladium(II) (0.5Og, 0.65mmol) was added and the reaction was heated to 8O0C for 2 hours. Aqueous work-up, followed by silica gel chromatography (0-30% EtOAc in hexanes), gave the title compound.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1215205-50-7, its application will become more common.

Reference:
Patent; AMIRA PHARMACEUTICALS, INC.; HUTCHINSON, John Howard; SEIDERS, Thomas Jon; WANG, Bowei; ARRUDA, Jeannie M.; ROPPE, Jeffrey Roger; PARR, Timothy; WO2010/141761; (2010); A2;,
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Adding a certain compound to certain chemical reactions, such as: 1186-73-8, name is Trimethyl methanetricarboxylate, belongs to esters-buliding-blocks 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 1186-73-8, Recommanded Product: Trimethyl methanetricarboxylate

N-benzyl-3-isopropyl-7-methoxy-6-(3-methoxypropoxy)tetralin-1-imine (1 g, 2.53 mmol) and trimethyl methanetricarboxylate (1.44 g, 7.6 mmol) were dissolved in diglyme (10 mL). The reaction mixture was stirred at 180 C in a microwave reactor for 30 minutes. Ethyl acetate (20 mL), followed by H2O (30 mL) were added to the reaction mixture. The separated organic layer was washed with H2O (2 x 20 mL), saturated aqueous brine solution (2 x 20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude residue was purified by normal phase SiO2; chromatography (0 to 70 % EtO Ac/hexanes) to give methyl 1-benzyl-4-hydroxy-5-isopropyl-9-methoxy-8-(3-methoxypropoxy)-2-oxo-1,2,5,6-tetrahydrobenzo[h]quinoline-3-carboxylate as a yellow oil (560 mg, 42% yield, m/z: 522 [M+H] observed).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Trimethyl methanetricarboxylate, and friends who are interested can also refer to it.

Reference:
Patent; ARBUTUS BIOPHARMA, INC.; CHEN, Shuai; DORSEY, Bruce D.; FAN, Yi; GOTCHEV, Dimitar B.; QUINTERO, Jorge; (252 pag.)WO2019/177937; (2019); A1;,
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