* 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.
With potassium fluoride; tri-tert-butyl phosphine In 1,4-dioxane; hexane at 65 - 70℃; for 4 h;
A solution of 5-bromofuraldehyde (2.43 g, 13.9 mmoles), 4-(methoxycarbonyl)phenylboronic acid (2.50 g, 13.9 mmoles), tris(dibenzylideneacetone)palladium (0) (192 mg, 0.2 mmoles) and potassium fluoride (2.42 g, 41.7 mmoles) in 1,4-dioxane (100 ml) was added with a solution of tri-toert-butylphosphine in hexane (10percent by weight, 101 mg, 0.5 mmoles). After heating at 65-70°C for 4 hours, the mixture was cooled to room temperature and treated with methylene chloride (150 ml). After stirring for 10 minutes, the mixture was filtered through Celite and the filtrate was EPO <DP n="13"/>concentrated under reduced pressure. The residue was purified by flash silica gel chromatography eluting with an ethyl acetate-hexane mixture (1 : 1) to give 4-(5-formyl-furan-2-yl)-benzoic acid methyl ester (2.6 g, 81percent yield).1H NMR (300 MHz, CDCl3): δ 9.70 (s, IH), 8.10 (d, 2H), 7.90 (d, 2H), 7.35 (d, IH), 6.95 (d, IH), 3.98 (s, 3H).
78%
With palladium diacetate; sodium carbonate In water; acetone at 20℃; for 0.416667 h;
To a solution of sodium carbonate (588.2 mg, 5.55 mmol) in H2O /acetone (278 mL/ 555 mL) was added 5-bromo-2-furaldehyde (1.9 g, 11 mmol), p-(methoxycarbonyl)phenyl boronic acid (2.0 g, 11 mmol) followed by palladium acetate(24.9 mg, 0.111 mmol) in acetone (278 ml). The reaction mixture was stirred at room temperature for 25 min. The reactionwas quenched by diluting with EtOAc (855 mL) and the organic layer was washed with 1 M HCl (500 mL) twice andwith brine (500 mL) once. The organic layer was dried over Na2SO4 and filtered with silica gel, which was concentratedin vacuo. The residue was purified by flash column chromatography (CH2Cl2/hexane = 9/ 1) to give compound 9 as whitesolid (2.0 g, 8.7 mmol, 78percent)
73%
With Pd(N,N-dimethyl-β-alaninate)2; sodium carbonate In ethanol; water at 120℃; for 0.166667 h; Microwave irradiation; Sealed tube
General procedure: To a solution of the appropriate bromo-substituted heterocyclic aldehydes 17a (1.0 mmol) in EtOH/H2O 5:3 (tot 12 mL) in a 35 mL CEM microwave vessel, the correspondent boronic acids 18c-d (1.2 mmol), Na2CO3 2M (2.0 mmol) and Pd(N,N-Dimethyl β-alaninate)2 (5 molpercent) were added. The vessel was capped and placed in a microwave reactor and the reaction carried out with the following method in dynamic mode: 120° C, 10 min, 50W, with high stirring. After completion the vessel was allowed to cool to room temperature and the mixture was extracted with EtOAc (3 X 10 mL). The organic phase was collected, dried over anhydrous Na2SO4, and the solvent evaporated under vacuum. The crude product (containing a small portion of the ethyl ester as a transesterification product) was then purified via silica gel column chromatography (petroleum ether/EtOAc elution gradient from a 90/10 ratio to a 80/20 ratio) to obtain the pure compounds (yield 40-60percent) (Scheme 1).
Reference：
[1] Patent: WO2006/66846, 2006, A1, . Location in patent: Page/Page column 11; 12
[2] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 9, p. 1562 - 1565
[3] European Journal of Medicinal Chemistry, 2015, vol. 101, p. 63 - 70
2
[ 27329-70-0 ]
[ 619-44-3 ]
[ 53355-29-6 ]
Yield
Reaction Conditions
Operation in experiment
75%
With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; water at 100℃; Inert atmosphere
General procedure: A mixture of substituted iodobenzene (2 mmol), (5-formylfuran-2-yl)boronic acid (420 mg, 3mmol, 1.5 equiv), Pd(Ph3P)2Cl2 (0.1 mmol, 0.05 equiv, 70 mg) and potassium carbonate (6 mmol,3 equiv, 828 mg) in dioxone/H2O (6 mL/2 mL) was stirred at 100 °C under argon atmosphereuntil the starting material was consumed (typically 20 h). The reaction mixture was then diluted with 25 mL of saturated brine. The mixture was then extracted with EtOAc (25 mL × 2), and the organic layers were combined, dried over Na2SO4. The concentrated crude product was purifie dby column chromatography to afford c2a-e. The second step is the same as procedure A.
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 6, p. 1024 - 1029
[2] Patent: CN106977474, 2017, A, . Location in patent: Paragraph 0034; 0037; 0038
[3] Chemical Biology and Drug Design, 2018, vol. 91, # 1, p. 257 - 268
3
[ 1899-24-7 ]
[ 619-44-3 ]
[ 53355-29-6 ]
Yield
Reaction Conditions
Operation in experiment
78%
With potassium phosphate In N,N-dimethyl acetamide at 60℃; for 24 h; Irradiation; Green chemistry
General procedure: To a solution of 1 (0.3 mmol) and 2 (0.45mmol) in DMA (5 mL) was added 3wtpercent Pd/CeO2 (80 mg). The reaction mixture was stirred under incandescent light (0.79 Wcm-2) irradiation at 60°C for 24h. After reaction (monitored by TLC), when the reaction is complete, in test tube extraction and centrifugal separation allows for isolation of the desired product, while the catalyst can be washed with ethanol and water, dried under vacuum, and reused for the next run. After completion of the reaction (monitored by TLC), water (5 mL) was added and the mixture was extracted with EtOAc (3 × 5 mL). The combined organic phase was dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by chromatography on silica gel (10:1 petroleum ether/EtOAc) to give the target product.
Reference：
[1] Chinese Chemical Letters, 2018, vol. 29, # 6, p. 903 - 906
4
[ 1899-24-7 ]
[ 13716-12-6 ]
[ 99768-12-4 ]
[ 53355-29-6 ]
Yield
Reaction Conditions
Operation in experiment
81%
With potassium fluoride In hexane; dichloromethane
A. 4-(5-Formyl-furan-2-yl)-benzoic Acid Methyl Ester To a solution of 5-bromofuraldehyde (2.43 g, 13.9 mmol), 4-(methoxycarbonyl)phenyl boronic acid (2.50 g, 13.9 mmol), tris(dibenzylideneacetone)dipalladium(0) (192 mg, 0.21 mmol) and potassium fluoride (2.42 g, 41.7 mmol) in 1,4-doxane (100 ml) was added a solution of tri-t-butylphosphine in hexane (10 weight percent, 1.01 g, 0.5 mmol). After heating at 65-70° C. for 4 hours, the mixture was cooled to room temperature and treated with dichloromethane (150 ml). After stirring for 10 minutes, the mixture was filtered through a pad of celite and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel eluding with ethyl acetate-hexane (1:1) to provide 4-(5-formyl-furan-2-yl)-benzoic acid methyl ester (2.6 g, 81percent yield).
Reference：
[1] Patent: US2004/2526, 2004, A1,
5
[ 67-56-1 ]
[ 39245-15-3 ]
[ 53355-29-6 ]
Yield
Reaction Conditions
Operation in experiment
85%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran
(2) The prepared 4- (5-formylfuran-2-yl) benzoic acid (0.250 g, 1.16 mmol)EDCI (0.265 g, 1.39 mmol),DMAP (0.07 g, 0.058 mmol) was dissolved in 25 mL of dry tetrahydrofuran,To this was added 2 ml of anhydrous methanol,The reaction was complete by TLC detection to 4- (5-formylfuran-2-yl) benzoic acid.Rotate the solvent,The target product was obtained by silica gel column chromatography4- (5-formyl-2-furyl)Benzoate(0.227 g, white solid, 85percent)
Reference：
[1] Patent: CN106565643, 2017, A, . Location in patent: Paragraph 0047; 0050
6
[ 619-44-3 ]
[ 378185-02-5 ]
[ 53355-29-6 ]
Reference：
[1] Synthesis, 2001, # 11, p. 1681 - 1685
7
[ 2689-65-8 ]
[ 619-44-3 ]
[ 53355-29-6 ]
Reference：
[1] Synlett, 2005, # 2, p. 267 - 270
8
[ 27329-70-0 ]
[ 619-42-1 ]
[ 53355-29-6 ]
Reference：
[1] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 17, p. 4585 - 4600
[2] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 13, p. 2159 - 2161
9
[ 13529-27-6 ]
[ 53355-29-6 ]
Reference：
[1] Synthesis, 2001, # 11, p. 1681 - 1685
With potassium fluoride; tri-tert-butyl phosphine;tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; hexane; at 65 - 70℃; for 4h;
A solution of 5-bromofuraldehyde (2.43 g, 13.9 mmoles), 4-(methoxycarbonyl)phenylboronic acid (2.50 g, 13.9 mmoles), tris(dibenzylideneacetone)palladium (0) (192 mg, 0.2 mmoles) and potassium fluoride (2.42 g, 41.7 mmoles) in 1,4-dioxane (100 ml) was added with a solution of tri-t°rt-butylphosphine in hexane (10% by weight, 101 mg, 0.5 mmoles). After heating at 65-70C for 4 hours, the mixture was cooled to room temperature and treated with methylene chloride (150 ml). After stirring for 10 minutes, the mixture was filtered through Celite and the filtrate was EPO <DP n="13"/>concentrated under reduced pressure. The residue was purified by flash silica gel chromatography eluting with an ethyl acetate-hexane mixture (1 : 1) to give 4-(5-formyl-furan-2-yl)-benzoic acid methyl ester (2.6 g, 81% yield).1H NMR (300 MHz, CDCl3): delta 9.70 (s, IH), 8.10 (d, 2H), 7.90 (d, 2H), 7.35 (d, IH), 6.95 (d, IH), 3.98 (s, 3H).
78%
With palladium diacetate; sodium carbonate; In water; acetone; at 20℃; for 0.416667h;
To a solution of sodium carbonate (588.2 mg, 5.55 mmol) in H2O /acetone (278 mL/ 555 mL) was added 5-bromo-2-furaldehyde (1.9 g, 11 mmol), p-(methoxycarbonyl)phenyl boronic acid (2.0 g, 11 mmol) followed by palladium acetate(24.9 mg, 0.111 mmol) in acetone (278 ml). The reaction mixture was stirred at room temperature for 25 min. The reactionwas quenched by diluting with EtOAc (855 mL) and the organic layer was washed with 1 M HCl (500 mL) twice andwith brine (500 mL) once. The organic layer was dried over Na2SO4 and filtered with silica gel, which was concentratedin vacuo. The residue was purified by flash column chromatography (CH2Cl2/hexane = 9/ 1) to give compound 9 as whitesolid (2.0 g, 8.7 mmol, 78%)
73%
With Pd(N,N-dimethyl-beta-alaninate)2; sodium carbonate; In ethanol; water; at 120℃; for 0.166667h;Microwave irradiation; Sealed tube;
General procedure: To a solution of the appropriate bromo-substituted heterocyclic aldehydes 17a (1.0 mmol) in EtOH/H2O 5:3 (tot 12 mL) in a 35 mL CEM microwave vessel, the correspondent boronic acids 18c-d (1.2 mmol), Na2CO3 2M (2.0 mmol) and Pd(N,N-Dimethyl beta-alaninate)2 (5 mol%) were added. The vessel was capped and placed in a microwave reactor and the reaction carried out with the following method in dynamic mode: 120 C, 10 min, 50W, with high stirring. After completion the vessel was allowed to cool to room temperature and the mixture was extracted with EtOAc (3 X 10 mL). The organic phase was collected, dried over anhydrous Na2SO4, and the solvent evaporated under vacuum. The crude product (containing a small portion of the ethyl ester as a transesterification product) was then purified via silica gel column chromatography (petroleum ether/EtOAc elution gradient from a 90/10 ratio to a 80/20 ratio) to obtain the pure compounds (yield 40-60%) (Scheme 1).
4-{5-[3-(3-morpholino-4-yl-propyl)-4-oxo-2-thioxo-thiazolidine-5-ylidenemethyl]-furan-2-yl}-benzoic acid methyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
25%
piperidine; In ethanol; for 6h;Heating / reflux;
A solution of <strong>[53355-29-6]4-(5-formyl-furan-2-yl)-benzoic acid methyl ester</strong> (59 mg, 0.27 mmoles) and 3-(3-morpholino-4-yl-propyl)-2-thioxo-thiazolidine-4-one (72 mg, 0.27 mmoles) in ethanol (10 ml) was added with piperidine (1 drop). After heating under reflux for 6 hours, the mixture was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography eluting with 10% methanol-methylene chloride to give the title compound (32 mg, 25%yield). EPO <DP n="14"/>1H NMR (300 MHz, DMSO-d6): delta 8.15 (d, 2H), 7.75 (d, 2H), 7.50 (s, IH), 6.95-7.05 (m, 2H), 4.20 (t, 2H), 3.95 (s, 3H), 3.90 (t, 2H), 3.58-3.75 (m, 2H), 2.30-2.60 (m, 6H), 1.80-2.00 (m, 2H).
4-[5-(3-Benzyl-4-oxo-2-thioxo-thiazolidin-5-ylidenemethyl)-furan-2-yl]-benzoic Acid Methyl Ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
69%
In ethanol;
B. 4-[5-(3-Benzyl-4-oxo-2-thioxo-thiazolidin-5-ylidenemethyl)-furan-2-yl]-benzoic Acid Methyl Ester To a solution of <strong>[53355-29-6]4-(5-formyl-furan-2-yl)-benzoic acid methyl ester</strong> (115 mg, 0.5 mmol) and 3-benzyl-2-thioxo-thiazolidin-4-one (112 mg, 0.5 mmol) in ethanol (10 ml) was added piperidine (1 drop). After heating at reflux for 30 minutes, the mixture was cooled to 0-5 C. The solid was filtered, washed with cold ethanol (2*5 ml), and dried under vacuum to give the title compound (150 mg, 69% yield).
4-{5-[4-Oxo-2-thioxo-3-(3,4,5-trimethoxy-benzyl)-thiazolidin-5-ylidenemethyl]-furan-2-yl}-benzoic Acid Methyl Ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
37%
In ethanol;
D. 4-{5-[4-Oxo-2-thioxo-3-(3,4,5-trimethoxy-benzyl)-thiazolidin-5-ylidenemethyl]-furan-2-yl}-benzoic Acid Methyl Ester To a solution of <strong>[53355-29-6]4-(5-formyl-furan-2-yl)-benzoic acid methyl ester</strong> (108 mg, 0.5 mmol) and 2-thioxo-3-(3,4,5-trimethoxy-benzyl)-thiazolidin-4-one (157 mg, 0.5 mmol) in ethanol (10 ml) was added piperidine (1 drop). After heating at reflux for 4 hours, the mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel eluding with 10% methanol-dichloromethane to give the title compound (98 mg, 37% yield).
4-{5-[3-(3-Morpholin-4-yl-propyl)-4-oxo-2-thioxo-thiazolidin-5-ylidenemethyl]-furan-2-yl}-benzoic Acid Methyl Ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
25%
In ethanol;
B. 4-{5-[3-(3-Morpholin-4-yl-propyl)-4-oxo-2-thioxo-thiazolidin-5-ylidenemethyl]-furan-2-yl}-benzoic Acid Methyl Ester To a solution of <strong>[53355-29-6]4-(5-formyl-furan-2-yl)-benzoic acid methyl ester</strong> (59 mg, 0.27 mmol) and 3-(3-morpholin-4yl-propyl)-2-thioxo-thiazolidin-4-one (72 mg, 0.27 mmol) in ethanol (10 ml) was added piperidine (1 drop). After heating at reflux for 6 hours, the mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel eluding with 10% methanol-dichloromethane to give the title compound (32 mg, 25% yield).
4-[5-(2,4-Dioxo-thiazolidin-5-ylidenemethyl)-furan-2-yl]-benzoic Acid Methyl Ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
77%
In ethanol;
Example 7 4-[5-(2,4-Dioxo-thiazolidin-5-ylidenemethyl)-furan-2-yl]-benzoic Acid Methyl Ester To a solution of <strong>[53355-29-6]4-(5-formyl-furan-2-yl)-benzoic acid methyl ester</strong> (477 mg, 2.2 mmol) and 2,4-thiazolidinedione (259 mg, 2.2 mmol) in ethanol (15 ml) was added piperidine (1 drop). After heating at reflux for 4 hours, the mixture was cooled to room temperature. The solid was filtered, washed with cold ethanol (2*5 ml), and dried under the vacuum to give the title compound (534 mg, 77% yield).
With potassium fluoride;tris-(dibenzylideneacetone)dipalladium(0); In hexane; dichloromethane;
A. 4-(5-Formyl-furan-2-yl)-benzoic Acid Methyl Ester To a solution of 5-bromofuraldehyde (2.43 g, 13.9 mmol), 4-(methoxycarbonyl)phenyl boronic acid (2.50 g, 13.9 mmol), tris(dibenzylideneacetone)dipalladium(0) (192 mg, 0.21 mmol) and potassium fluoride (2.42 g, 41.7 mmol) in 1,4-doxane (100 ml) was added a solution of tri-t-butylphosphine in hexane (10 weight %, 1.01 g, 0.5 mmol). After heating at 65-70 C. for 4 hours, the mixture was cooled to room temperature and treated with dichloromethane (150 ml). After stirring for 10 minutes, the mixture was filtered through a pad of celite and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel eluding with ethyl acetate-hexane (1:1) to provide 4-(5-formyl-furan-2-yl)-benzoic acid methyl ester (2.6 g, 81% yield).
With hydrogenchloride; lithium hydroxide; In methanol; water;
B. 4-(5-Formyl-furan-2-yl)-benzoic Acid To a solution of <strong>[53355-29-6]4-(5-formyl-furan-2-yl)-benzoic acid methyl ester</strong> (230 mg, 1 mmol) in a mixture of methanol (6 ml) and water (2 ml) was added lithium hydroxide (82 mg, 2 mmol). After stirring for 6 hours at room temperature, the solution was acidified to pH 2 by addition of 1 M hydrochloric acid. After concentrating under reduced pressure, the residue was purified by flash chromatography on silica gel eluding with 10% methanol-dichloromethane to give 4-(5-formyl-furan-2-yl)-benzoic acid (198 mg, 92% yield).
With acetic acid; 3-amino propanoic acid; at 100℃; for 1h;
General procedure: A mixture of methyl 3-(5-formylfuran-2-yl)benzoate (3 mmol), beta-alanine (3 mmol), and compound 10 (3 mmol)were heated at 100 C for 1 h in acetic acid (10 mL). Upon completion of the reaction, the mixture was cooled, the reaction was quenched with water (20 mL), and the precipitate was filtered off. The solid was washed with water and methanol and then finally dried with diethyl ether to give the desired compound as a yellow solid: yield, 92%.
methyl 4-(5-((2-(2-cyanoacetyl)hydrazono)methyl)furan-2-yl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
53%
In ethanol; at 120℃; for 0.75h;Microwave irradiation; Sealed tube;
General procedure: A solution of the appropriate aldehydes 19a-i (1.0 mmol) in ethanol (20 mL) was prepared in a 35 mL CEM microwave vessel. The correspondent hydrazides 20a-f (1.0 mmol) were added, the vessel was capped and placed in a microwave reactor and the reaction carried out with the following method in dynamic mode: 120 C, 45 min, 130 W. After completion the vessel was allowed to cool to room temperature and then placed in a refrigerator for 1 h. The product precipitated from the cold reaction mixture was collected by vacuum filtration and dried on filter. Purification was achieved by recrystallization with methanol, yielding the pure product as a colored solid ranging from yellow to red color (yield 40-60%) (Scheme 1, Table 1).
With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; water; at 100℃;Inert atmosphere;
General procedure: A mixture of substituted iodobenzene (2 mmol), (5-formylfuran-2-yl)boronic acid (420 mg, 3mmol, 1.5 equiv), Pd(Ph3P)2Cl2 (0.1 mmol, 0.05 equiv, 70 mg) and potassium carbonate (6 mmol,3 equiv, 828 mg) in dioxone/H2O (6 mL/2 mL) was stirred at 100 C under argon atmosphereuntil the starting material was consumed (typically 20 h). The reaction mixture was then diluted with 25 mL of saturated brine. The mixture was then extracted with EtOAc (25 mL × 2), and the organic layers were combined, dried over Na2SO4. The concentrated crude product was purifie dby column chromatography to afford c2a-e. The second step is the same as procedure A.
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In water; acetonitrile; at 60℃; for 1h;Inert atmosphere;
General procedure: Substituted iodobenzene (1.0 equiv.),(5-aldehyde furan-2-yl) phenylboronic acid (1.5 equivalents)Na2CO3 (2.0 equivalents) and Pd (PPh3) 2Cl2 (0.1 equivalents) were dissolved with MeCN / H2O = 1: 1 (5 ml / mmol)Displacement of nitrogen 3 times,Then moved to 60 C,After 1 h, TLC monitored whether the reaction was complete,After completion of the reaction,The filtrate was concentrated under reduced pressure,Followed by column chromatography to give the compound to replace 5-phenylfuran-2-aldehyde furan (25)The yield is about 68-87%.
(E)-2-cyano-N-(3,4-dimethylphenyl)-3-(5-(4-(methyl methanoate)phenyl)furan-2-yl)acrylamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With piperidine; In ethanol; at 80℃; for 2h;
General procedure: A solution of compound 22 (1.0 equiv)And compound 25 (1.0 equiv.) Were dissolved in EtOH (5 ml / mmol)Adding a catalytic amount of piperidine,And then heated to 80 C reaction,2h after the reaction is complete,Solid filtration,The filter cake was separated by column chromatography to obtain the condensation product,The yield was 75-90%.
methyl (E)-4-(5-((2-(hydrazinethiocarbonyl)hydrazono)methyl)furan-2-yl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55%
In 1,4-dioxane; water; at 90℃;
(3)Thiocarbazide(0.500 g, 4.72 mmol)Was dissolved in a mixed solution of 50 ml of 1,4-dioxane and water (volume ratio = 1: 1)Heated to 90 C,Add to itMethyl 4- (5-formyl-2-furyl) benzoate(0.050 g, 0.2 mmol).After completion of the reaction by TLC, the solvent was spun dry, to which 20 ml of hot water was added.Filter while still hot and the filter cake is washed with hot water.Purification gave the title compoundMethyl (E) -4- (5- ((2- (hydrazinecarbonyl) hydrazono) methyl)Furan-2-yl)Benzoate0.035g.(Yellow solid, melting point: 179-181 C, yield: 55%).
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In tetrahydrofuran;
(2) The prepared 4- (5-formylfuran-2-yl) benzoic acid (0.250 g, 1.16 mmol)EDCI (0.265 g, 1.39 mmol),DMAP (0.07 g, 0.058 mmol) was dissolved in 25 mL of dry tetrahydrofuran,To this was added 2 ml of anhydrous methanol,The reaction was complete by TLC detection to 4- (5-formylfuran-2-yl) benzoic acid.Rotate the solvent,The target product was obtained by silica gel column chromatography4- (5-formyl-2-furyl)Benzoate(0.227 g, white solid, 85%)
(Z)-3-(5-((5-(4-(methoxycarbonyl)phenyl)furan-2-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)propanoic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
63%
With sodium acetate; acetic acid; at 105℃;Inert atmosphere;
General procedure: To a mixture of aldehyde (1.0 mmol), <strong>[7025-19-6]3-(4-oxo-2-thioxothiazolidin-3-yl)propanoic acid</strong> (205 mg,1.0 mmol) or 3-(2-(1H-tetrazol-5-yl)ethyl)-2-thioxothiazolidin-4-one (229 mg, 1.0 mmol) and NaOAc (820 mg, 10.0 mmol) was added acetic acid (5.0 mL). The reaction was allowed to stir at 105 C for 0.5h - 12h, then cooled to room temperature. To the reaction was added water (15mL). The resulting mixture was sonicated to give yellow-orange slurry. After filtration, the solid was washed with water (75 mL) and dried under high vacuum to yield the corresponding product as a red fine powder.
A mixture of 1,3-indandione 6 (1.3 g, 8.7 mmol) and aldehyde 9 (2.0 g, 8.7 mmol) dissolved in acetic acid (35 mL) at110 C for 5 min and then 3-aminocrotonate 8 (1.0 g, 8.7 mmol) was added to the mixture, which was heated to 110 for 1 min. The reaction was quenched by adding water (35 mL). The supernatant was removed and to the precipitate wasadded 35 mL water and then the supernatant was removed. This procedure to remove water soluble residues was furtherrepeated twice. The precipitate was dissolved with 25 mg/mL concentration in 150 mL EtOAc/hexane = 1/2 at roomtemperature. The recrystallized sample was dissolved with 100 mg/mL concentration in 50 mL EtOH/H2O = 4/1 at 80 and recrystallized, which was further repeated once. Then the recrystallized sample was purified by flash columnchromatography (EtOAc/hexane = 1/ 4) to give compound 10 as dark red solid (135.49 mg, 0.298 mmol, 10 %)
With potassium phosphate; In N,N-dimethyl acetamide; at 60℃; for 24h;Irradiation; Green chemistry;
General procedure: To a solution of 1 (0.3 mmol) and 2 (0.45mmol) in DMA (5 mL) was added 3wt% Pd/CeO2 (80 mg). The reaction mixture was stirred under incandescent light (0.79 Wcm-2) irradiation at 60C for 24h. After reaction (monitored by TLC), when the reaction is complete, in test tube extraction and centrifugal separation allows for isolation of the desired product, while the catalyst can be washed with ethanol and water, dried under vacuum, and reused for the next run. After completion of the reaction (monitored by TLC), water (5 mL) was added and the mixture was extracted with EtOAc (3 × 5 mL). The combined organic phase was dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by chromatography on silica gel (10:1 petroleum ether/EtOAc) to give the target product.
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