* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference:
[1] Chemistry Letters, 1980, p. 483 - 486
2
[ 1571-08-0 ]
[ 7377-26-6 ]
Yield
Reaction Conditions
Operation in experiment
90%
at 60℃; for 10 h; Melt
[Example 1] 75percent methyl-4-formylbenzoate (methyl-4-formylbenzoate 16. 4g) was melted at 60°C, and 1.5 molar equivalent of chlorine gas (C12) was added thereto while bubbling for 10 hours to obtain methyl-4-chloroformylbenzoate with the yield of 90percent. 19.8g of methyl-4-chloroformylbenzoate dissolved in 80g of toluene at 60°C was dropwisely added into 10percent aqueous ammonia for 2 hours, which includes 10 molar equivalent of ammonia with respect to methyl-4- chloroformylbenzoate. In this reaction, the reaction temperature was maintained at 5 to 20°C. Then, cooling of the reactant was stopped to increase the temperature of the reactant to room temperature. The reactant was filtered to obtain white crystalline methyl-4-carbamoylbenzoate with the yield of 98percent and the purity of 95percent. 1N aqueous sodium hydroxide solution including 5 molar equivalent of sodium hydroxide with respect to methyl-4-carbamoylbenzoate is cooled to 0°C, and 17. 9g of methyl-4-carbamoylbenzoate was added thereto. While maintaining the temperature of the reactant at 0 to 10°C, 10percent aqueous NaOCI solution including 1.05 molar equivalent of NaOCI was added into the reactant for 30 minutes, and the reaction was continued for 2 hours. Then, the temperature of the reactant was increased to 50°C, and maintained for 1 hour. By adding aqueous NaOH, the pH of the reactant was adjusted to 4, and solid target compound was precipitated. By filtering the reactant, the target compound, p- aminobenzoic acid was obtained with the yield of 95percent.
Stage #1: With dicarbonyl(pentamethylcyclopentadienyl)(4-methoxyphenyl)iron In dichloromethane for 4 h; Inert atmosphere; Irradiation; Schlenk technique Stage #2: With sodium hydroxide In methanol; waterSchlenk technique; Inert atmosphere
General procedure: In a Schlenk tube under 1 atm of argon, a solution of the substrate (2 mmol, 1 equiv), the precatalyst (0.04 mmol, 0.02 equiv), and the silane (3 mmol, 1.5 equiv) in methylene chloride (15 mL) was irradiated for 4h. After removal of the solvent, methanol (5 mL) and aqueous NaOH solution (2.5 M, 5 mL) were added and the resulting suspension was stirred overnight. Neutralization with aqueous HCl solution (2 M, 30 mL) and brine (20 mL) followed by standard workup gave the desired products as pure yellow oils.
Reference:
[1] Journal of Organometallic Chemistry, 2004, vol. 689, # 3, p. 639 - 646
16
[ 1571-08-0 ]
[ 62642-62-0 ]
Reference:
[1] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 2, p. 179 - 190
17
[ 1571-08-0 ]
[ 106261-48-7 ]
Reference:
[1] Patent: WO2011/8788, 2011, A1,
[2] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 2, p. 179 - 190
18
[ 1122-62-9 ]
[ 1571-08-0 ]
[ 158014-74-5 ]
Yield
Reaction Conditions
Operation in experiment
50%
With ammonia; sodium hydroxide In ethanol; water at 20℃; for 17 h;
Round bottom flask 4-methoxycarbonyl benzaldehyde (1.0g, 6.1mmol) and 2-acetyl pyridine (1.37ml, 12.2mmol) were dissolved in 25ml of ethanol.Then 30percent NH3were placed in a round flask, that the solution (1ml) and NaOH (0.488g, 12.2mmol) was dissolved in a minimal amount of water.Put the clear liquid solution of NaOH runners ttuieotgo is light yellow, and after about an hour and caught the red.In about 17 hours at room temperature, open the entrance to the round bottom flask and stirred haenotgo allow air to enter.Over time, the precipitate produced was more yellow.After the reaction was terminated, and then dissolved into water (50ml) and neutralized with HCl.The precipitate was filtered out and washed with water by filtration.And placed in 50ml of ethanol was refluxed for 1 hour and filtered and dried under vacuum (yield: 50percent).
With ammonia; sodium hydroxide; In ethanol; water; at 20℃; for 17h;
Round bottom flask 4-methoxycarbonyl benzaldehyde (1.0g, 6.1mmol) and 2-acetyl pyridine (1.37ml, 12.2mmol) were dissolved in 25ml of ethanol.Then 30% NH3were placed in a round flask, that the solution (1ml) and NaOH (0.488g, 12.2mmol) was dissolved in a minimal amount of water.Put the clear liquid solution of NaOH runners ttuieotgo is light yellow, and after about an hour and caught the red.In about 17 hours at room temperature, open the entrance to the round bottom flask and stirred haenotgo allow air to enter.Over time, the precipitate produced was more yellow.After the reaction was terminated, and then dissolved into water (50ml) and neutralized with HCl.The precipitate was filtered out and washed with water by filtration.And placed in 50ml of ethanol was refluxed for 1 hour and filtered and dried under vacuum (yield: 50%).
With ammonium chloride;molecular sieve; In tetrahydrofuran; dichloromethane;
Preparative Example 26 Methyl 4-acryloylbenzoate STR48 A 1.0 M solution (100 ml) of vinylmagnesium bromide in tetrahydrofuran was added dropwise into a solution of 13.6 g of methyl terephthalaldehydate in 150 ml of tetrahydrofuran at -78 C. The resulting mixture was stirred at the same temperature for 30 minutes, quenched with a saturated aqueous solution of ammonium chloride, and extracted with ethyl acetate (200 ml*2). The organic layers were combined, washed with brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated, and the resulting crude product was purified by silica gel column chromatography to give 11.6 g of an allyl alcohol. Then, 11.6 g of the allyl alcohol was dissolved in 600 ml of dichloromethane, followed by the addition thereto of 3 g of molecular sieve (3A) and 27 g of pyridinium bichromate. The resulting mixture was stirred at room temperature for 4 hours, and filtered through Celite. The filtrate was concentrated, and the resulting crude product was purified by silica gel column chromatography to give 5.5 g of the title compound as colorless crystals. 1 H-NMR (CDCl3, 400 MHz) delta; 3.96 (s, 3H), 6.00 (d, 1H, J=10.4 Hz), 6.46 (d, 1H, J=17.2 Hz), 7.14 (dd, 1H, J=10.4, 17.2 Hz), 7.98 (d, 2H, J=8.4 Hz), 8.14 (d, 2H, J=8.4 Hz).
4-[(2-Methoxy-5-phenylcarbamoyl-phenylamino)-methyl]-benzoic acid methyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Example 221 4-[(2-Methoxy-5-phenylcarbamoyl-phenylamino)-methyl]-benzoic acid methyl ester The title compound has been made using the procedure of Example 50, but using 3-amino-4-methoxy-N-phenyl benzamide or 4-carbomethoxybenzaldehyde as starting materials, which are commercially available from Aldrich; m.p. 170-172 C.
1,1-dimethylethyl 2-[[[[4-(methoxycarbonyl)phenyl]methyl]amino]methyl]-1-pyrrolidinecarboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium tris(acetoxy)borohydride; acetic acid; In 1,1-dichloroethane; at 20℃; for 17h;
A solution of 1,1-dimethylethyl 2-(aminomethyl)-1-pyrrolidinecarboxylate (1000 mg, 5 mmol) and methyl 4-formylbenzoate (820 mg, 5 mmol) in dichloroethane was stirred as acetic acid (450 mg, 7.5 mmol) and sodium triacetoxyborohydride (1271 mg, 6 mmol) were added sequentially at ambient temperature. After stirring at ambient temperature for 17 hours, treated with a saturated aqueous solution of sodium bicarbonate and extracted with EtOAc. The combined organic extracts were dried and concentrated. Purification by flash chromatography afforded 1,1-dimethylethyl 2-[[[[4-(methoxycarbonyl)phenyl]methyl]amino]methyl]-1-pyrrolidinecarboxylate (800 mg), 1H NMR (CDCl3) 7.98 (d, 2H), 3.37 (d, 2H), 3.91 (s, 3H), 3.82 (s, 2H), 3.36 (m, 2H), 2.72 (m, 1H), 1.82 (m, 3H), 1.44 (m, 2H) ppm.
Step 1: A solution of methyl 4-formylbenzoate (8 g, 48.7 mmol, 1 eq) in THF (150 ml_) was cooled to -78C. Methyl magnesium bromide (3M in Et2O, 16.2 ml_, 48.7 mmol, 1 eq) was added dropwise to the solution over 15 min. The resulting mixture was stirred 16h, allowing it to warm to room temperature. Upon quenching the reaction with saturated NH4CI, the organic layer was removed, washed with saturated NH4CI, dried over anhydrous MgSO4, filtered and evaporated to afford a crude yellow oil which was subjected to silica gel chromatography (0% to 50% EtOAc in hexanes) to afford the desired product as a free-flowing pale yellow oil.
To a solution of tert-butyl P,P-dimethylphosphonoacetate (Fluka, 1.43 g, 6.4 mmol) in THF (40 mL) was added NaH (Alderich, 60percent, 536 mg, 13.4 mmol) portionwise at rt over 30 min. Methyl 4-formylbenzoate (Alderich, 1.0 g, 6.09 mmol) was then added and the reaction mixture was stirred at rt for 4 hrs. The reaction was quenched with water and extracted with EtOAc. The organic layer was separated, and dried over Na2SO4. The mixture was then concentrated to give the crude 4-((E)-2-tert-butoxycarbonyl-vinyl)-benzoic acid methyl ester (1.89 g, 118percent).
General procedure: In a Schlenk tube under 1 atm of argon, a solution of the substrate (2 mmol, 1 equiv), the precatalyst (0.04 mmol, 0.02 equiv), and the silane (3 mmol, 1.5 equiv) in methylene chloride (15 mL) was irradiated for 4h. After removal of the solvent, methanol (5 mL) and aqueous NaOH solution (2.5 M, 5 mL) were added and the resulting suspension was stirred overnight. Neutralization with aqueous HCl solution (2 M, 30 mL) and brine (20 mL) followed by standard workup gave the desired products as pure yellow oils.
General procedure: A mixture of corresponding hydrazinylpyridazine 1 or 5 (1 mmol) and aldehyde 2 (1.1 mmol) in ethanol (5 mL) was heated at 60 oC for 0.5 h. The formation of hydrazone was checked by TLC and the reaction mixture was cooled to rt. Oxone (1.5 mmol) was added to the mixture at rt followed by tetramethyl ammonium bromide (0.2 mmol) and the resulting mixture was heated at 60 oC for another 5 h. The mixture was cooled to rt and extracted with dichloromethane (2 × 25 mL), dried over anhydrous sodium sulphate and concentrated to obtain a residue which was purified by column chromatography using hexane/ethyl acetate as eluent to furnish the desired triazolopyridazines 4 and 7.
In ethanol; at 60℃; for 0.5h;
General procedure: A mixture of corresponding hydrazinylpyridazine 1 or 5 (1 mmol) and aldehyde 2 (1.1 mmol) in ethanol (5 mL) was heated at 60 C for 0.5 h. The formation of hydrazone was checked by TLC and the reaction mixture was cooled to rt. Oxone (1.5 mmol) was added to the mixture at rt followed by tetramethyl ammonium bromide (0.2 mmol) and the resulting mixture was heated at 60 C for another 5 h. The mixture was cooled to rt and extracted with dichloromethane (2 × 25 mL), dried over anhydrous sodium sulfate and concentrated to obtain a residue which was purified by column chromatography using hexane/ethyl acetate as eluent to furnish the desired triazolopyridazines 4 and 7 (See reference no; 7 for supporting information).
With 4-methylpiperidin; In acetonitrile; at 90℃; for 48h;
Step1.A mixture of <strong>[939-79-7]4-methyl-3-nitrobenzonitrile</strong> (24) (6.48 g, 40 mmol), methyl terephthaldehyde (25) (6.56 g, 40 mmol), and 4-methylpiperidine (3 mL) in CH3CN (90 mL) was heated at 90 C for 48 h. The reaction was cooled to rt and quenched with water (90 mL). The resulting precipitate was collected by filtration and recrystallization from CH3CN:water (1:1) to give stilbene26(9.17 g, 74%) as a yellow solid. mp 207-209 C.1H NMR (500 MHz, DMSO-d6)3.87 (s, 3H), 7.61 (s, 2H), 7.79 (d,J= 7.8 Hz, 2H), 8.01 (d,J= 8.3 Hz, 2H), 8.22 (brs, 2H), 8.58 (s, 1H);13C NMR (125.7 MHz, DMSO-d6)52.39, 111.28, 117.22, 124.44, 127.79, 128.99, 129.44, 129.84, 129.92, 135.23, 135.81, 136.51, 140.58, 148.07, 166.00.
ethyl 4-(cyclohexylamino)-3-(4-(methoxycarbonyl)-benzylamino)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
General procedure: SI, Figure 4. General procedure of the reductive amination reactions: synthesis of AA9-AA24 compounds (Tables 1 and 2). The <strong>[347174-05-4]ethyl 3-amino-4-(cyclohexylamino)benzoate</strong> (AA1) and derivatives (1 equiv.)and benzaldehyde (1 equiv) were heated in DCE for 1h at 80 oC in the presence of molecular sieves (4 A), then the mixture was cooled down to room temperature before addition of the NaBH(OAc)3 (1.6 equiv.) in small portions over 3h. The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 17h. The reaction mixture was quenched with aqueous saturated NaHCO3, and the product was extracted with EtOAc. The EtOAc extract was dried (MgSO4), and the solvent was evaporated. The residue was purified by flash-column chromatography on silica gel, using a mixture of solvent of DCM: MeOH (50:1), to provide the desired AA9-AA24 compounds (Tables 1-2).
tert-butyl 2-((4-(methoxycarbonyl)benzyl)amino)-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
44.3%
With sodium tris(acetoxy)borohydride; acetic acid; at 20℃; for 12.5h;
A solution of tert-butyl2-amino-6,7-dthydrothiazolo[5 ,4-cjpyridine-5(4H)-carboxylate (0.500 g, 1.958 mmol), methyl 4-formylbenzoate (0.354 g, 2.154 mmol) and acetic acid (0.135 mL, 2.350 mmol) in dichloromethane (20 mL) was stirred at the room temperature for 30 mm, and mixed with sodium triacetoxyborohydride (0.830 g, 3.9 16 mmol). The reaction mixture was stirred at the same temperature for additional 12 hr. Then, water was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with aqueous saturated sodium bicarbonate solution, dried with anhydrous Mg504, filtered, and concentrated in vacuo. The residue was chromatographed (5i02, 12 g cartridge; ethyl acetate / hexane = 0 % to 40 %) to give tertbutyl2-((4-(methoxycarbonyl)benzyl)amino)-6,7-dihydrothiazolo[5 ,4-cjpyridine-5(4H)-carb oxylate as white solid (0.350 g, 44.3 %).
methyl 4-(2-amino-3-cyano-6-hydroxy-5,8-dioxo-7-undecyl-5,8-dihydro-4H-chromen-4-yl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
With triethylamine; In ethanol; for 2h;Reflux;
General procedure: To a mixture of 0.1mmol of malononitrile, 0.1mmol of the corresponding aldehyde, and 10mol % of Et3N in 5mL of EtOH were added 30mg of <strong>[550-24-3]embelin</strong> (0.1mmol). The reaction mixture was stirred and refluxed until disappearance of the starting benzoquinone. The solvent was removed under vacuum, and the crude product was purified by preparative-TLC to yield the corresponding dihydropyran derivative.
1-Methyl-2-acetylimidazole (1.8 g, 16.36 mmol) and LiOH (392 mg, 16.36 mmol) were stirred in MeOH (100 mL) before methyl 4-formylbenzoate (2.6 g, 16.36 mmol) was added. After 30 min a thick yellow precipitate was formed. The precipitate was filtered and dried under vacuum to yield 2c as a yellow solid (63%).
63%
With lithium hydroxide; In methanol; for 0.5h;
2c: 1 -Methyl-2-acetylimidazole (1.8 g, 16.36 mmol) and LiOH (392 mg, 16.36 mmol) were stirred in MeOH (100 mL) before methyl 4-formylbenzoate (2.6 g, 16.36 mmol) was added. After 30 min a thick yellow precipitate was formed. The precipitate was filtered and dried under vacuum to yield 2c as a yellow solid (63%).
tert-butyl 4-(4-(methoxycarbonyl)benzyl)-3,3-dimethylpiperazine-1-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium triacetoxyborohydride; In dichloromethane; at 20℃;
To a stirred solution of amine compound 2(0.5 g, 1 eq) and aldehyde 1(0.421 g, 1.1 eq) in DCM (10 mL), sodium triacetoxyborohydride (STAB) (0.693 g, 1 .4 eq) was added. The reaction mixture was stirred at room temperature for overnight; the reaction progress was monitored by TLC and LCMS. After completion of reaction, the reaction mixture was partitioned between DCM and water. The organic layers were separated, washed with water and brine, dried over Na2504 and evaporated to get the crude product which was purified by silica gel column chromatography to afford the desired compound 3.
5-(4-methylbenzoate)-2-thioxo-2,3,5,12-tetrahydro-1H-1,3,12-triazanaphthacene-4,6,11-trione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
58%
In ethanol; at 80℃; for 13h;
General procedure: Synthesis of product (4a-o): A mixture of, 2-hydroxy-1,4-naphthoquinone (0.174 g,1 mmol), aromatic aldehydes (1 mmol), 6-amino-2-thiouracil (0.143 g, 1 mmol) and 10 mLEtOH in a 50 mL flask was heated at reflux for 12-15 hours. After reaction completion(monitored by TLC, ethyl acetate/n-hexane, 1:1), the reaction mixture was cooled to roomtemperature and filtered to give the crude product. Then the solid was washed with ethanolto give product (4) in good to high yields.
4-[(3,5-dimethylisoxazol-4-ylamino)methyl]benzoic acid methyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
43%
With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 20℃; for 16h;
To stirred solution of 4-Formyl-benzoic acid methyl ester (1) (500 mg, 4.452 mmol) in DCE (10 mL) were added 3,5-Dimethyl-isoxazol-4-ylamine (2) (543 mg, 4.452 mmol) and AcOH (0.252 mL, 4.452 mmol) and the resulting mixture was stirred for 15 minutes. To it was then added Sodium triacetoxyborohydride (1.41 g, 6.679 mmol) and the reaction mixture was stirred at room temperature for 16 hours. It was then diluted with DCM, washed with aqueous saturated NaHC03 solution, water, dried over Na2S04 and concentrated under reduced pressure. Crude thus obtained was purified by column chromatography (silica, gradient: 30-40% EtOAc in Hexane) to afford the Intermediate 3 (500 mg, 43%) as yellow oil.
methyl 4-(2,3-dihydrofuro[3,2-c]pyridin-2-yl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
61%
With tetrabutyl ammonium fluoride; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 60℃;
General procedure: To a stirred mixture of 1.00 mmol of nitropicoline 35 or 63, 1.20 mmol of the appropriate benzaldehyde, and 1.5 mmol of Huenig's base in THF (7 mL/g of nitropicoline 35/63) was added 1.3 mmol of a 1 M THF solution of TBAF. The resulting mixture was heated 60 C for 1.5e2.0 h in the case of 2,3-dihydrofuro[3,2-c] pyridines or for 18 h in the case of 2,3-dihydrofuro[2,3-b]pyridines. After cooling to room temperature, the reactions were quenched with sat. aqueous NH4Cl. The solution was extracted with EtOAc, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel chromatography as specified above.
methyl 4-([3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]amino}methyl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
81%
With sodium tris(acetoxy)borohydride; acetic acid; In chloroform; at 20℃;
General procedure: Amixture of methyl 4-formylbenzoate (1) (1.1 equivalents) and amine R1NH2 (a-d) (1.0 equivalent)was dissolved in dry CHCl3. Sodium triacetoxyborohydride (2.8 equivalents) and AcOH (sixequivalents) were added to this solution, and the resulting solution was stirred at room temperaturefor 2±3 h. The reaction mixture was quenched with an ice-cold saturated solution of NaHCO3 (topH 7), and extracted with CHCl3. The combined organic layers were dried over Na2SO4, filtered,and concentrated under vacuum. The residue was dissolved in ethyl acetate, and the product wasprecipitated with hexane. The solid was ltered and washed with ethyl acetate/hexane.Methyl 4-([3-(4-methyl-1H-imidazol-1-yl)-5-(triuoromethyl)phenyl]amino}methyl)benzoate (6a) wassynthesized from methyl 4-formylbenzoate (1) and compound a as a white solid. The yield was 81%.1H-NMR (DMSO-d6, 500 MHz) : 8.13 (d, J = 1.0 Hz, 1H), 7.96 (d, J = 8.3 Hz, 2H), 7.54 (d, J = 8.3 Hz,2H), 7.42 (s, 1H), 7.14 (s, 1H), 7.04 (s, 1H), 6.96 (s, 1H), 6.86 (s, 1H), 4.54 (d, J = 6.1 Hz, 2H), 4.51-4.56 (m,2H), 3.85 (s, 3H), 2.15 (s, 3H); 13C-NMR (DMSO-d6, 125 MHz) : 166.6, 150.7, 145.6, 139.1, 138.9, 135.3,129.9, 127.9, 114.6, 107.6, 106.1, 103.8, 52.5, 46.2, 14.0; HRMS (ESI+) m/z calculated for C20H19F3N3O2[M + H]+ 390,1424, found 390.1425.
With sodium tris(acetoxy)borohydride; acetic acid; In chloroform; at 20℃;
General procedure: Amixture of methyl 4-formylbenzoate (1) (1.1 equivalents) and amine R1NH2 (a-d) (1.0 equivalent)was dissolved in dry CHCl3. Sodium triacetoxyborohydride (2.8 equivalents) and AcOH (sixequivalents) were added to this solution, and the resulting solution was stirred at room temperaturefor 2±3 h. The reaction mixture was quenched with an ice-cold saturated solution of NaHCO3 (topH 7), and extracted with CHCl3. The combined organic layers were dried over Na2SO4, filtered,and concentrated under vacuum. The residue was dissolved in ethyl acetate, and the product was precipitated with hexane. The solid was ltered and washed with ethyl acetate/hexane.