Name: 531-81-7|2-Oxo-2H-chromene-3-carboxylic acid|98%
Brand: Ambeed
SKU: A440648
Price: 5.0 USD
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[ 531-81-7 ]
[ 3757-06-0 ]

Yield	Reaction Conditions	Operation in experiment
99%	With thionyl chloride at 80℃; for 4h;
98%	With thionyl chloride for 2h; Heating;
98%	With thionyl chloride for 24h; Heating;

98%	With thionyl chloride
97.7%	With thionyl chloride for 2h; Reflux;	1.3 (3) Intermediate Coumarin Intercalator FragranceSynthesis of Coumarin-3-Formyl Chloride: In a clean round-bottomed flask, 2.8 g of the obtained coumarin-3-carboxylic acid, 20 mL of freshly distilled SOCl2 was refluxed in an oil bath for 2 h, followed by TLC, and the remaining SOCl2 was removed by rotatory evaporation under reduced pressure to obtain 3 g of pale yellow solid. 97.7%.
90%	With thionyl chloride In chloroform
87.8%	With thionyl chloride; N,N-dimethyl-formamide at 20℃; for 2h;
83%	With thionyl chloride at 20℃; for 1h;	2.3.2 General preparation of compounds 3-acyl chloride coumarin derivatives 3 A mixture of 3-carboxycoumarin 2a (10.0 mmol, 1.901 g), anhydrous thionylchloride (4.0 mL) and anhydrous DMF (0.1 mL) was stirred at room temperature for 1h. The reaction was complete detected by TLC and the solvent was removed underreduced pressure to afford target compound 3a (1.447 g, 83%) as white solid.
83%	With thionyl chloride at 20℃; for 1h;	4.3.2. General preparation of compounds 3-acyl chloride coumarin derivatives 3 A mixture of 3-carboxycoumarin 2a (10.0 mmol, 1.901 g), an- hydrous thionyl chloride (4 mL) and anhydrous DMF (0.1 mL) was stirred at room temperature for 1 h. The reaction was complete detected by TLC and the solvent was removed under reduced pres- sure to afford target compound 3a (1.447 g, 83%) as white solid. The synthesis process of 3b was similar to 3a .
82%	With pyridine; thionyl chloride at 70℃; for 6h;	1 Coumarin-3-formyl chloride (4) The coumarin-3-carboxylic acid (4 g, 21.0 mmol) was dissolved in 15 mL of thionyl chloride, and 4 drops of pyridine was added dropwise. After stirring at 70 ° C for 6 h, the excess amount of thionyl chloride was distilled off under reduced pressure Yellow solid 1.8g. The crude product was recrystallized from petroleum ether to give 2.25 g of a white solid, 82% yield,
81.2%	With pyridine; thionyl chloride for 6h; Reflux;	2-Oxo-2H-chromene-3-carbonyl chloride (4) Compound 3 (4 g, 19 mmol) and pyridine (0.3 mL) wasdissolved in sulfoxide chloride (15 mL) and refluxed 6 h.After cooling, the mixture was removed redundant sulfoxidechloride by reduced pressure to give crude product.Finally, the crude product was purified by recrystallizedfrom petroleum ether to give faint yellow solid 4 (3.3 g,81.2%), m.p. 143.6-145.8 °C (Mo et al. 2006).
80%	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h;
	With thionyl chloride
	With thionyl chloride; chloroform
	With chloroform; phosphorus(V) chloride
	With thionyl chloride In benzene for 1.5h; Heating;
	With thionyl chloride for 3h; Heating;
	With thionyl chloride for 3h;
	With pyridine; oxalyl dichloride In toluene
	With thionyl chloride In benzene
	With thionyl chloride; triethylamine In dichloromethane at 0 - 20℃; for 0.666667h;
	With thionyl chloride; triethylamine In toluene at 0℃; for 0.5h;
	With thionyl chloride
	With thionyl chloride Heating;
	With thionyl chloride at 80℃; for 2h;
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide
	With thionyl chloride
	With thionyl chloride	4.a (Endo)-N-(8-aza-8-methylbicyclo[3.2.1]octan-3-yl) chromone-3-carboxamide (a) A mixture of chromone-3-carboxylic acid (1.25 g) and thionyl chloride (6 ml) was heated at reflux for 5 minutes. The reaction mixture was then diluted with cyclohexane (15 ml) and ice-cooled. The crystalline precipitate was collected by filtration, washed with cyclohexane and dried under vacuum to give chromone-3-carbonyl chloride (1.2 g).
	With thionyl chloride In dichloromethane; Petroleum ether	22.a (a) (a) Coumarin-3-carbonyl chloride Coumarin-3-carboxylic acid (2.1 g, 10 m mole) was suspended in dry dichloromethane (10 ml) and heated at reflux for 2 h with thionyl chloride (5 ml). After this time a small amount of insoluble material was filtered off and petroleum ether 60°-80° C. (35 ml) was added to the filtrate. The acid chloride was filtered, washed with ether and dried (1.63 g, 71%), mp 138°-41° C.; νmax (CHCl3) 1790, 1740, 1610, 1570 cm-1; δ (CDCl3) 7.30-8.10 (4H, m, phenyls), 8.95 (1H, s, coumarin 4-H).
	With thionyl chloride In N,N-dimethyl-formamide for 0.0333333h; microwave irradiation;
	With thionyl chloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 20h;
3.95 g	With thionyl chloride for 3h; Heating;
	With thionyl chloride for 3h;
	With thionyl chloride Reflux;
	With thionyl chloride at 100℃; for 2h;
	With thionyl chloride at 80℃; for 2h; Inert atmosphere;
	With thionyl chloride Reflux;	6.1. General procedure for the synthesis of derivatives 1-58 General procedure: 3-Carbonyl coumarins were obtained by Knoevenagel cyclization between substituted salicylaldehydes (1 mmol) and methyl acetoacetate (1 mmol) or ethyl benzoylacetate (1 mmol) in ethanol (25 mL) with catalytic amounts of piperidine. The ethyl ester of coumarin-3-carboxylic acid was prepared by Knoevenagel reaction between diethyl malonate (1 mmol) and the appropriate salicylaldehyde (1 mmol) with catalytic amounts of piperidine in ethanol (50 mL). Then, if there was an hydroxyl group at position 7, etherification was performed by adding a suitable benzyl bromide (1 mmol) or cycloheptyl bromide (1 mmol), and potassium carbonate (1 mmol) in anhydrous acetone (100 mL), using N,N'-dicyclohexyl-18-crown-6-ether (1 mmol) as a chelating agent. Final products were purified by chromatography. Ethyl ester derivatives (1 mmol) were dissolved and stirred at room temperature in a solution of LiOH.H2O (6 mmol) in H2O/MeOH (1:5, v/v; 50 mL); then HCl 3 N (50 mL) was added. The suspension was filtered and the solid was dried under vacuum. 3-Carboxyhydrazido derivatives were obtained by dissolving at reflux 3-coumarin carboxylic acid (1 mmol) in thionyl chloride (20 mL). After solvent evaporation under vacuum, the reactive acyl chloride (1 mmol) was reacted with a suitable hydrazine hydrochloride (2 mmol) in the presence of sodium acetate (2 mmol) in H2O/CH3CN (1/4, v/v).
	With thionyl chloride for 2h; Reflux;
	With thionyl chloride for 2h; Reflux;	2.4. The general procedures for the synthesis of substituted coumarin-3-carboxylic acid ester compounds General procedure: The substituted coumarin-3-carboxylic acid ethyl esters (Scheme 2) were prepared by Knoevenagel reaction. To a mixture of diethyl malonate (1 mmol) and the appropriate salicylaldehyde (1 mmol) in ethanol (10 ml) was added piperidine (5 mol %) and the reaction mixture was stirred at the room temperature. The progress of the reaction was monitored by TLC. After completion of the reaction, the solvent was removed under vacuum and the residue was purified by chromatography. The obtained substituted coumarin-3-carboxylic acid ethyl ester (2 mmol) was dissolved in 10% NaOH (50 ml), then 3 N HCl (50 ml) was added the mixture. The suspension was filtered and dried under vacuum to provide substituted coumarin-3-carboxylic acid. The coumarin-3-carboxylic acid (2 mmol) was added to thionyl chloride (30 ml), the reaction mixture was refluxed for about 2 h, the thionyl chloride was removed under vacuum. The desired substituted coumarin-3-carbonyl chloride was obtained. To a mixture of substituted coumarin-3-carbonyl chloride (2 mmol) and toluene (20 ml) or ethyl ether (20 ml) was added dropwise appropriate alcohol (2 mmol) and then the reaction mixture was refluxed for about 12 h. The solvent was removed under vacuum and the residue was purified by chromatography.
	With thionyl chloride for 3h; Reflux;	1 synthesis of CFL33, isoquinolin-1-yl 2-oxo-2H-1-benzopyran-3-carboxylate 1.0 g of the commercially available2-oxo-2H-1-benzopyran-3-carboxylic acid and 10 ml of thionyl chloride were refluxed for 3 h. The resulting solution was evaporated under reduced pressure. The residue was suspended in 10 ml anhydrous toluene. The solvent was eliminated by distillation under reduced pressure. The two last steps were repeated twice. The residue was dispersed in 10 ml dioxane. To this suspension were added 1-hydroxyquinoleine (1.1 q.) and anhydrous pyridine (1.1 eq.). After 90 min stirring at room temperature, the solvent was removed by distillation under reduced pressure. The residue was solubilized in chloroform and the organic phase was washed three times with HCl 0.1N, then dried over MgSO4. The solvent was evaporated under reduced pressure and the residue obtained was recrystallized in ethyl acetate. white solid ; m.p. 197-200°C 1H NMR (500 MHz) DMSO-d6 : 6.87 (d, 1H, 4-H isoquin.), 7.47 (t, 1H, 6-H coumar.), 7.52 (d, 1H, 8-H coumar.), 7.58 (t, 1H, 7-H isoquin.), 7.75 (m, 2H, 7-H coumar. + 5-H isoquin.), 7.84 (m, 2H, 6-H + 3-H isoquin.), 7.93 (d, 1H, 5-H coumar.), 8.16 (d, 1H, 8-H isoquin.), 8.56 (s, 1H, 4-H coumar.).
	With thionyl chloride for 3h; Reflux;	1 Example 1 : synthesis of CFL33 , isoquinolin- 1 -yl 2-oxo-2H- 1 -benzopyran-3-carboxylate Example 1 : synthesis of CFL33 , isoquinolin- 1 -yl 2-oxo-2H- 1 -benzopyran-3-carboxylate 1.0 g of the commercially available 2-oxo-2H-l-benzopyran-3-carboxylic acid and 10 ml of thionyl chloride were refluxed for 3 h. The resulting solution was evaporated under reduced pressure. The residue was suspended in 10 ml anhydrous toluene. The solvent was eliminated by distillation under reduced pressure. The two last steps were repeated twice. The residue was dispersed in 10 ml dioxane. To this suspension were added 1- hydroxyquinoleine (1.1 eq.) and anhydrous pyridine (1.1 eq.). After 90 min stirring at room temperature, the solvent was removed by distillation under reduced pressure. The residue was solubilized in chloroform and the organic phase was washed three times with HC1 0.1N, then dried over MgSC^. The solvent was evaporated under reduced pressure and the residue obtained was recrystallized in ethyl acetate.white solid ; m.p. 197-200°C1H NMR (500 MHz) DMSO-d6 : 6.87 (d, IH, 4-H isoquin.), 7.47 (t, IH, 6-H coumar.), 7.52 (d, IH, 8-H coumar.), 7.58 (t, IH, 7-H isoquin.), 7.75 (m, 2H, 7-H coumar. + 5-H isoquin.), 7.84 (m, 2H, 6-H + 3-H isoquin.), 7.93 (d, IH, 5-H coumar.), 8.16 (d, IH, 8-H isoquin.), 8.56 (s, IH, 4-H coumar.).
	With bis(trichloromethyl) carbonate In dichloromethane at 40℃; for 3h;	2.4 Synthesis and characterization of sensors CS1∼CS3 Coumarin-3-carboxylic acid (3 mmol) and bis(trichlormethyl)carbonate (BTC, 1.5 mmol) were added into dry dichloromethane (15 mL). Then the reaction mixture was stirred at 40 °C for 3 h under reflux. In this process, the coumarin-3-carboxylic acid has been converted to the coumarin-3-carbonyl chloride, which did not need separating. Then, dry and powdered KSCN (4 mmol) and PEG-400 (0.1 mL, as phase transfer catalyst) were added to the reaction solution and stirred it at room temperature for 2 h, and the inorganic salts were filtered out. The filtrate was a solution of the corresponding coumarin-3-carbonyl isothiocyanate, which did not need separating also. Then 2.8 mmol of phenylhydrazine was added to the filtrate solution and stirred at room temperature for 3 h, yielding the precipitate of CS1. After evaporating the solvent in a vacuum, the precipitate was filtered, washed with 75% ethanol three times, and recrystallized with ethanol to get white crystal of CS1. The other compounds CS2 and CS3 were prepared by similar procedures.
	With thionyl chloride In neat (no solvent) at 100℃; for 2.5h; Inert atmosphere;
	With thionyl chloride Reflux;	4.1.1 General procedure for the preparation of compounds 9 and 10 General procedure: Compound 3 (1mmol) was added to thionyl chloride (5ml) and the mixture was refluxed for 3-5 h. After completion of the reaction, thionyl chloride was removed with simple distillation to give appropriate coumarin-3-carbonyl chloride derivative. The crude product was used directly without further purification. In the next step, appropriate amine (1-benzylpiperidin-4-amine or 2-(1-benzylpiperidin-4-yl)ethanamine) (1mmol) and potassium carbonate (2 mmol) were dissolved in dry toluene (15 ml). The mixture was refluxed for 6-12 h, and then the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography using petroleum ether-ethyl acetate (8:2) as a mobile phase to give the pure product.
	With thionyl chloride for 2h; Reflux;
	With thionyl chloride In dichloromethane at 0 - 5℃;
	With thionyl chloride Reflux;
	With thionyl chloride for 1h; Reflux;
	With thionyl chloride at 100℃; for 2.5h; Inert atmosphere;
	With thionyl chloride for 3h; Reflux;
	With thionyl chloride In dichloromethane for 8h; Reflux;
	With thionyl chloride for 4h; Reflux;	Preparation of 2-oxo-N-(thiazol-2-yl)-2H-chromene-3-carboxamide (C1) 2-Oxo-2H-chromene-3-carboxylic acid (3) (0.190 g, 1.0 mmol) and 8 mL SOCl2 were added into a 25-mL single-necked flask equipped with a water-cooled condenser and tail gas absorption device and heated under reflux for 4 h. After cooling to room temperature, the SOCl2 was evaporated under reduced pressure. 2-Aminothiazole (0.095 g, 0.95 mmol) in 2 mL of CH2Cl2 was added dropwise to the above 2-oxo-2H-chromene-3-carbonyl chloride in 10 mL CH2Cl2 cooled at 0 °C. The mixture was stirred for 1 h at 0 °C, then for 8 h at r.t. The solvent was evaporated under reduced pressure. The crude product was subjected to chromatography on silica gel (200-300 mesh) and eluted with a mixture of petroleum ether and ethyl acetate to afford C1 as light yellow crystals (0.099 g, 38.3 % yield). m.p. 278-280 °C. 1H NMR (DMSO-d6, 600 MHz), d: 12.05 (s, 1H), 9.04 (s, 1H), 8.05-8.06 (m, 1H), 7.81-7.85 (m, 1H), 7.58-7.59 (m, 2H), 7.50-7.52 (m, 1H), 7.38 (d, J = 3.5 Hz, 1H). 13C NMR (DMSO-d6, 150 MHz), d: 160.9, 154.5, 149.0, 138.7, 135.4, 131.1, 126.0, 118.8, 116.9, 115.4. HRMS m/z (ESI): calcd for C13H9N2O3S [M+H]+ 273.0328, found 273.0332.
	With thionyl chloride Reflux;	General procedure for the synthesis of Coumarinyl thioureas (2a-2l) Coumarin-3-carboxylic acid (2.6 mM) was placed in a 100 mL two necked round bottom flask, fitted with a reflux condenser and a gas trap. Then (0.23 mL, 0.003 mol) thionyl chloride was added and the reaction mixture was heated under reflux for 2-3 h to give acid chloride. To a stirred solution of potassium thiocyanate in 20 mL dry acetone, placed in a 250 mL two necked round bottom flask fitted with a reflux condenser, freshly prepared acid chloride (2.0 mM) was added drop wise and the mixture was refluxed for 30 min. After the initial reaction has subsided, a solution of substituted aniline (0.0026 mol) in 20 mL dry acetone was added slowly with constant stirring to the reaction mixture, followed by 1-2 h reflux. The progress of the reaction was monitored by thin layer chromatography. After the completion of the reaction, the reaction mixture was poured into crushed ice. The thiourea formed was precipitated as solid which was then filtered off, washed well with cold distilled water, dried and recrystallized from ethanol.
	With thionyl chloride In N,N-dimethyl-formamide Reflux;
	With thionyl chloride Reflux;	5.4. General procedure for the synthesis of compounds 4a-o General procedure: Compounds 3a-o (1mmol) were added to thionyl chloride (5ml) and the mixture was refluxed for 5-6 h. After completion of the reaction, thionyl chloride was removed with simple distillation to give appropriate coumarin-3-carboxylic acid chloride. The crude product was used directly without further purification. In the next step, the corresponding acid chloride, tryptamine (1 mmol) and potassium carbonate (2 mmol) were suspended in dry toluene (15ml). The mixture was refluxed for 14-16 h under argon atmosphere. After completion of the reaction (monitored by TLC), the solvent was removed under reduced pressure and the residue was washed with water and dried to give compounds 4a-o. Alternatively the same reaction could carry out in acetonitrile under microwave irradiations at 85°C for 5 min.
	With thionyl chloride for 1h; Reflux;	1.1 (1) Compound 2a (i.e., coumarin-3-carboxylic acid ) (1.9 g, 10 mmol) was dissolved in 15 mL of SOCl2,The reaction solution was refluxed for 1 hour,The remaining SOCl2 was removed by spin-The resulting product compound 4a,Without purification,Directly to the next reaction.
	With thionyl chloride
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h; Schlenk technique;
	With bis(trichloromethyl) carbonate In dichloromethane at 40℃; for 3h;
	With thionyl chloride for 7h; Reflux;
	With thionyl chloride for 4h; Reflux;	Preparation of N,N-bis(2-chloroethyl)-2-oxo-2H-chromene-3-carboxamide (5a) According to literature [53], coumarin-3-carboxylic acid (0.190 g, 1 mmol) and thionyl chloride (8 mL) were added to a 50-mL round-bottomed flask equipped with condenser and tail gas absorption device. The reaction mixture was stirred at reflux for 4 h. Then, thionyl chloride was removed under reduced pressure to afford coumarin-3-carbonyl chloride (4a) as white powder. M.p.: 142-143°C (144-145°C[54]). Compound 4a should be prepared immediately prior to use. Solution of Et3N (0.606 g, 6 mmol), bis(2-chloroethyl)amine hydrochloride(0.178 g, 1 mmol) in CH3CN (20 mL) was added dropwise to solution of 4a in CH3CN (20 mL) under N2 and cooled in an ice bath. Then, the reaction mixture wasstirred at room temperature for 8 h. The crude product was purified by silica gelcolumn chromatography using ethyl acetate:petroleum ether (1:3, v/v) as eluent,yielding white solid (0.092 g, 29% yield).
	With thionyl chloride at 80℃; for 4h; Inert atmosphere;	12 4.5.12 (+-)-N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2-(dimethylamino)ethyl)-2-oxo-2H-chromene-3-carboxamide (19) A solution of 2-oxo-2H-chromene-3-carboxylic acid (323 mg, 1.70 mmol, 3.4 eq.) in SOCl2 (8 mL) was stirred under an argon atmosphere at 80 °C for 4 h. The reagent was evaporated under reduced pressure, and the oily residue was dried under vacuum for 30 min. Anhydrous pyridine (10 mL) was added under an argon atmosphere to dissolve the acyl chloride formed. A solution of 5 [ 15 ] (323 mg, 0.50 mmol, 1.0 eq.) in anhydrous pyridine (5 mL) was then added, and the mixture was stirred at room temperature for 72 h. The solvent was evaporated, and the residue was dissolved in CH2Cl2 (100 mL) and transferred into a separating funnel. The organic phase was washed with saturated aqueous NaHCO3 solution (2 x 70 mL), and saturated brine solution (100 mL), dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by reversed-phase column chromatography (Isolera Biotage system, SNAP Biotage KP-18-HS column) using a gradient of 0.1% TFA (aq) and MeCN as eluent. The fractions containing the product were combined and the organic solvent was evaporated under reduced pressure. The remaining aqueous solution was made alkaline using saturated aqueous solution of NaHCO3 (80 mL), transferred into a separating funnel, and extracted with CH2Cl2 (3 x 50 mL). The combined organic phases were dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. Yield: 19% (44 mg); white solid, mp 88-91 °C; Rf = 0.10 (CH2Cl2/MeOH = 9/1); 1H NMR (400 MHz, CDCl3): δ 0.76-0.89 (m, 0.4H), 1.09-1.20 (m, 0.6H), 1.67-2.14 (m, 7H), 2.20-2.26 (m, 1H), 2.34 (s, 2H), 2.40-2.47 (m, 1.3H), 2.62-2.66 (m, 0.7H), 2.81-3.65 (m, 12H), 2.57-2.66 (m, 1H), 7.11-7.21 (m, 4H), 7.29-7.34 (m, 1H), 7.36-7.38 (m, 1H), 7.47-7.53 (m, 1H), 7.56-7.61 (m, 1H), 7.75 (s, 0.4H), 7.82 (s, 0.6H); 13C NMR (100 MHz, CDCl3): δ 24.62, 28.24, 28.44, 34.44, 35.34, 36.59, 36.80, 36.94, 43.59, 45.64, 45.71, 46.58, 47.81, 51.87, 52.03, 53.13, 55.68, 56.14, 57.60, 66.97, 67.35, 116.84, 118.20, 118.27, 124.29, 124.32, 124.38, 124.49, 124.85, 125.81, 125.99, 126.38, 126.45, 128.32, 128.46, 132.57, 132.63, 141.34, 141.89, 142.10, 153.94, 157.94, 158.06, 165.32, 165.72; ESI-HRMS m/z calcd. for C29H36N3O3 [M+H]+ 474.2757, found 474.2750; IR (ATR) υ = 2931, 2823, 2772, 1709, 1631, 1607, 1573, 1466, 1434, 1365, 1306, 1255, 1201, 1171, 1118, 1018, 948, 825, 753, 738, 702 cm-1; HPLC purity, 95.2% at 254 nm (tR = 5.17 min).
	With thionyl chloride for 6h; Reflux;	Synthesis of 2-oxo-2H-chromene-3-carbonyl chloride General procedure: First, 5 mmol of salicylaldehyde (compound 1) dissolved in 10 ml dry ethanol. Next, 5 mmol of diethyl malonate (compound 2), 0.005 ml of glacial acetic acid and 0.05 ml of piperidine were added to the reaction mixture. This mixture was then refluxed for 6 h (monitored by TLC), and the resulting white precipitate was filtered and washed with cold ethanol several times, before being dried at ambient temperature to obtain compound 3. Next, this white precipitate was dissolved in 100 ml of 0.5% NaOH and refluxed for 2 h, until a clear solution was achieved. This solution was next acidified with HCl to reach a pH of 2, and cooled to 0 °C. In this way, a white precipitate was obtained, which was filtered and washed with cold ethanol, allowed to dry in ambient conditions and crystalized from ethanol (compound 4) (6.58 g, 82.2% yield) [29]. At last, to 2.5 mL of thionyl chloride in toluene was added 0.18 g of compound 4 (1 mmol) and the resulting mixture was refluxed at 80 °C for 6 h. Before the reaction was finished, the solvent of the reaction mixture was evaporated to finally collect 2-oxo-2H-chromene-3-carbonyl chloride (compound 5) without any further treatments.
	With oxalyl dichloride for 8h; Reflux;
	With oxalyl dichloride; 3,3-dichloro-1,2-diphenylcyclopropene; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Inert atmosphere;	Preparation of Weinreb amides (2a-d) and (5a-h) General procedure: To a solution of in situ generated CPI-Cl (generated by the treatment of 2,3 diphenylcyclopropenone (1.1 mmol) with oxalyl chloride (1 mmol) in Cl2Cl2) was added aryl/heterocyclic/Nα-protected amino acid (1 mmol), DIPEA (2 mmol) stirring at room temperature. After the formation of acid chloride solution of N,O-dimethylhydroxylamine (2 mmol) in CH 2 Cl 2 was added. After the completion of the reaction (determined by TLC), solvent was evaporated under vacuo and diluted with EtOAc, washed with 5% citric acid (10 mL x 2) and Na 2 CO 3 (10 mL x 2), water, brine and dried over anhydrous Na 2 SO 4 . After filteration, solvent was evaporated and purified by column chromatography using hexane and EtOAc as eluents.
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 23h; Inert atmosphere;	Typical Procedure for the Preparation of 1 To a suspension of coumarin-3-carboxylic acid (3.00 g, 15.8 mmol, 1.00 equiv.) in anhydrous CH2Cl2(70.0 mL) at 0 °C under an argon atmosphere, oxalyl chloride (1.60 mL, 19.0 mmol, 1.20 equiv.) andanhydrous DMF (2 drops) were added. The resulting suspension was warmed to room temperature andstirred for 23 h. The reaction solvent and volatile compounds were evaporated and dried under highvacuum for 1 h to give coumarin-3-carboxylic acid chloride which was used for the preparation of 1without purification. In a dried round bottom flask under argon atmosphere, 1,3-oxazolidin-2-one (1.37 g,15.8 mmol, 1.00 equiv.) was dissolved in anhydrous THF (80.0 mL) and cooled to -78 °C, and thenn-butyllithium (1.57 M in n-hexane solution) (10.6 mL, 16.6 mmol, 1.05 equiv.) was added dropwise and stirred for 30 min. The resulting suspension was warmed to 0 °C and stirred for 30 min. A solidcoumarin-3-carboxylic acid chloride (3.30 g, 15.8 mmol, 1.00 equiv.) was added to the reaction mixturein one portion under an argon stream. The resulting suspension was warmed to 0 °C and stirred for 30 min.The reaction mixture was allowed to warm to room temperature and stirred for 24 h. A colorlessprecipitate that had formed was collected by filtration and washed with water and EtOAc. The resultingcolorless powder was suspended in EtOAc and stirred for 1 h at 80 °C. A colorless powder was collectedby filteration and dried under high vacuum in the presence of P2O5 for 6 h to give 1 (2.63 g) in 64% yield.Compound 1: Colorless powder; mp 221-223 °C; Rf : 0.17 (1:1 hexane/EtOAc); IR (KBr) ν 3431, 3044,2990, 2925, 1775, 1727, 1689, 1384, 1339, 1208, 1117, 758 cm-1; 1H NMR (500 MHz, CDCl3) δ4.14-4.23 (2H, m), 4.49-4.59 (2H, m), 7.29-7.65 (4H, m), 7.93 (1H, s); 13C NMR (125 MHz, CDCl3) δ42.5, 62.8, 117.1, 118.0, 124.1, 124.9, 128.9, 133.4, 143.2, 152.9, 154.4, 157.8, 164.0; HRMS (ESI-TOF)Calcd for C13H9NO5 [M+Na]+: 282.0373; Found: 282.0394.
	With trichlorophosphate Reflux;
	With thionyl chloride for 12h; Reflux;	General procedure for the synthesisof coumarin-3-carbonyl chloride (8) Coumarin-3-carboxylic acid (1 mmol) and thionyl chloride(1.2 mmol) were refluxed for 12 h. The progress of the reaction was controled by TLC. After completion of the reaction,the excess of thionyl chloride was distilled and the product was obtained as yellow light solid that was used in the next step.
	With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 50℃; for 1h;	.3 General procedure for the synthesis of I, 7a-l General procedure: To the solution of 2,4-dichlorobenzoic acid (5a, 0.300g, 15.7mmol) in dichloromethane (30mL), 3 drops of dimethylformamide and 1mL of thionylchloride were added dropwise one by one. After reaction completed, monitored by TLC, the mixture was concentrated under vacuum and dichloromethane (4×10mL) was added to remove the excess thionyl chloride during evaporation. The resulting 2,4-dichlorobenzoyl chloride (6a) was subsequently treated with appropriate sulfonamide derivatives 4a-m (17mmol) in the presence of NaHCO3 (50mmol) in acetone at room temperature overnight. After reaction completed, acetone was evaporated and the residue was poured onto ice-water. The mixture was then extracted with ethyl acetate (3×30mL). The collected organic layer was washed by brine solutions, dried over magnesium sulfate, and concentrated under vacuum. The product was purified by column chromatography by using 40-50% ethyl acetate in petroleum ether.
	With thionyl chloride In dichloromethane at 0 - 20℃; for 4h;
	With phosgene In dichloromethane; N,N-dimethyl-formamide at 45℃; for 3h;
	With trichlorophosphate at 20℃; for 0.333333h;

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2
[ 531-81-7 ]
[ 10242-15-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	With calcium(II) nitrate tetrahydrate; acetic acid at 60℃; for 1h;	Nitration reaction procedure of coumarin derivatives (Entry 1-8 in table 2) General procedure: 6.2 mmol (1.0 g) of 1 was treated with 6.2 mmol of Ca(NO3)2·4H2O (1.5 g) in acetic acid as solvent, Then the mixture was heated in a boiling water bath (maintained at 60 oC) for 1 h. Coumarin derivatives were dissolved completely and the solution became dark red. It was immediately poured into a 10 ml of ice cold water. The turbid dark red solution was kept in a refrigerator. After four hours, the yellow crystals that separated were washed to free of acid with a minimum amount of ice cold water and then dried to give the desired product.
	With sulfuric acid; nitric acid
	With nitric acid

	With sulfuric acid; nitric acid at -10 - 0℃; for 1h;	6.1 Specific step 1: preparation of 6-nitro-coumarin-3-carboxylic acid IIIf Specific step 1: preparation of 6-nitro-coumarin-3-carboxylic acid IIIf (0080) 50g of coumarin-3-acid was dissolved in 240mL of concentrated sulfuric acid, cooled to -10°C, a mixed acid solution of concentrated nitric acid and concentrated sulfuric acid (80mL, wherein the volume ratio of concentrated nitric acid to concentrated sulfuric acid is 1:3) was added, the mixture was stirred at 0°C for 1 h, then the temperature was raised to room temperature and the mixture was reacted for further 1 h. The reaction solution was poured into 5000mL of ice water, stood for crystallization, the crystal was filtered, washed with the ice water, and dried to obtain 6-nitrocoumarin-3-carboxylic acid IIIf which was light yellow amorphous solid.
	With nitric acid

Reference： [1]Chaudhari, Hemchandra K.; Pahelkar, Akshata; Takale, Balaram S. [Tetrahedron Letters, 2017, vol. 58, # 43, p. 4107 - 4110]
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[5]Current Patent Assignee: ENDO PRODUCTS - US2683720, 1949, A

3
[ 1846-76-0 ]
[ 531-81-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium hydroxide In ethanol; lithium hydroxide monohydrate for 0.25h; Reflux;	1 Coumarin-3-carboxylic acid (3) In a 100 mL round bottom flask, 25 mL of 95% ethanol and NaOH solution were added (8 g of solid NaOH in 50 mL of water), 6 g (0.028 mol) of coumarin-3-carboxylic acid ethyl ester, and heated under reflux for 15 min. The reaction mixture was poured into 70 mL of aqueous hydrochloric acid with stirring, i.e., the crystals were precipitated. The crude crude coumarin-3-carboxylic acid was recrystallized from 50% ethanol to give 5.2 g of white crystalline coumarin-3-carboxylic acid in 95% yield,
92.6%	With sodium hydroxide In ethanol; lithium hydroxide monohydrate at 75℃; for 0.333333h;	1-3 Synthesis of the compound of formula 2: Add 2.5 g NaOH, 4 g coumarin-3-carboxylic acid ethyl ester, 30 ml 95% absolute ethanol and 10 ml water to a 100 ml round bottom flask, install in a reflux apparatus, and heat in an oil bath until the ester is dissolved, then 75 ° C. After continuous reflux for 20 min, the solution was allowed to cool for a while, and then transferred to a beaker containing 30 ml of concentrated hydrochloric acid and 50 ml of water, a large amount of white crystals were precipitated, which was cooled in ice water to be completely crystallized, and filtered. The crystal was washed several times with ice water and recrystallized from water to give 3.5 g of white needle crystals, yield 92.6%.
90%	With sodium hydroxide In ethanol; lithium hydroxide monohydrate for 0.25h; Reflux;

86.7%	With sodium hydroxide In ethanol for 2h; Heating;
86.2%	With lithium hydroxide monohydrate; sodium hydroxide In ethanol Reflux;	3 3. Compound B1--Synthesis of 3-coumarin carboxylic acid compounds Add 3-coumarin ethyl formate (4.0g, 18.3mmol), sodium hydroxide (3g, 75mmol), 20mL of 95% ethanol, and 10mL of water to a 100mL round-bottomed flask. After all the ester and sodium hydroxide are dissolved, reflux and stir, TLC tracking and detecting until the reaction is complete, the reaction is stopped. Pour the mixture while hot into dilute hydrochloric acid mixed with 15 mL concentrated hydrochloric acid and 50 mL water for acidification. A large amount of white crystals are precipitated. The crystals are completely precipitated by cooling in an ice-water bath; vacuum filtration, the product is washed with a small amount of ice water 2 Second, drained to obtain a crude product. After drying, it was weighed to obtain 3.0 g of product with a yield of 86.2%.
85%	With lithium hydroxide monohydrate; sodium hydroxide In ethanol for 6h; Reflux;
85%	With sodium hydroxide In lithium hydroxide monohydrate at 20℃; for 7 - 8h;	Procedure for the synthesis of coumarin-3-carboxylic acid Coumarin 3-carboxylic acid I was synthesized by reported procedure[2] with slight modification. To the stirred solution of ethyl 2-oxo-2H-1-benzopyran-3-carboxylate (1 eq.) in 10% (w/v in water) of sodium hydroxide was stirred at room temperature for about 7-8 hrs. The completion of the reaction was indicated by the single spot on TLC plate. Then reaction mixture was neutralized by 6 N hydrochloric acid and solid formed was filtered and washed thoroughly with water and dried. Yield: 85 %; White solid; m.p.: 188-190C; FT-IR (KBr, cm-1): 1655, 1710 (C=O). 1H NMR (400 MHz, CDCl3, δ ppm): 7.47-7.51 (q, 2H, Ar-H), 7.77-7.82 (m, 2H, Ar-H), 8.95 (s, 1H, Ar-H), 12.23 (s, 1H, OH). 13C NMR (100 MHz, CDCl3, δ ppm): 116.598, 118.533, 118.826, 125.597, 130.860, 134.772, 148.63, 154.43 160.73, 161.82.
84.8%	With sodium hydroxide In ethanol; lithium hydroxide monohydrate for 0.3h; Reflux;	Preparation of 2-Oxo-2H-chromene-3-carboxylic acid (3) To a solution of ethyl 2-oxo-2H-chromene-3-carboxylate (1) (2.000 g, 9.2 mmol) in EtOH/H2O 2:1 (v/v, 15 mL) was added 1.5 g NaOH and heated under reflux for 18 min. After cooling to room temperature, the solution was slowly poured into hydrochloric acid solution 20 % (v/v, 30 mL) and cooling to 0 °C gave a white crystalline deposit. The solid was collected by filtration and washed with cold water to afford 3 as white crystals, and finally dried in vacuo. (1.479 g, 84.8 %): m.p. 187-188 °C (lit. value 191-192 °C) [30]. ]. An analogous procedure starting with 2 gave 7-diethylamino-2-oxo-2H-chromene-3-carboxylic acid (4) (78.6 %); m.p. 236-238 °C (lit. value 228 °C) [31].
82%	With bromine In chloroform Heating;
82.5%	With sodium hydroxide In ethanol; lithium hydroxide monohydrate for 0.333333h; Reflux;	1.2 (2) Synthesis of the intermediate coumarin-3-carboxylic acid: In a clean round-bottomed flask, 4.0 g of the above-obtained ethyl coumarin-3-carboxylate, 5.0 g of sodium hydroxide, 25 mL of 95% absolute ethanol, and 10 mL of water were successively added and the oil bath was refluxed.After the ester was completely dissolved, reflux was continued for 20 min. Stop heating, cool to room temperature, transfer the reaction solution to an Erlenmeyer flask, add dilute hydrochloric acid dropwise, dribble while dripping, can see white crystals precipitated, ice bath cooling, crystallized completely, suction filtration, washing with a small amount of ice water 2 to 3 times. About 2.87 g of product was obtained after drying, with a yield of 82.5%.
82%	With sodium hydroxide In ethanol at 80℃; for 0.25h;	2.2.5. General synthetic procedure of compounds 12a-t General procedure: Compound 11 (5 mmol) in EtOH (5 mL) were added 10% NaOH (10mL). Next, the mixture was warmed to 80 °C and stirred for 15 min. The resulting mixture poured off in cold water to precipitate a large amount of solid product. The solid product was filtered off and recrystallized by EtOH to afford acid compounds 12a-t (except 12d, 12i, 12m, and 12q)in good yields.
78%	With potassium hydroxide In ethanol; lithium hydroxide monohydrate for 1h; Reflux;	4.1.2. Synthesis of Coumarin-3-carboxylic Acid (17) In 100 ml, RBF 3-carbethoxycoumarin (2.0 g) was dissolved in 30 ml of EtOH: H2O (1:1). To this solution, potassium hydroxide was added (5.0 eq). The reaction mass was stirred at reflux temperature for 1 hr. The progress of the reaction was monitored by using TLC (ethyl acetate/hexane: 50:50). After completion of the reaction, the reaction mixture was cooled to room temperature and acidified with 6M HCl solution. The white solid product precipitated out. The crude product was treated with n-hexane to remove non-polar impurities and recrystallized with ethanol. White solid (78% yield); Mp 188-190 °C; 1H-NMR (400 MHz, CDCl3) δ 7.31-7.85 (m, 4H, Ar-H), 8.44 (s, 1H, CH=C-), 12.25 (s, 1H, -COOH); IR (KBr): νmax 3465, 2951, 2846, 1730, 1602, 1542 cm-1; LC/MS (ESI) m/z 191.03 (M+H)+.
69.76%	With hydrogenchloride; lithium hydroxide monohydrate; sodium hydroxide	2.4. The general procedures for the synthesis of substituted coumarin-3-carboxylic acid ester compounds General procedure: The substituted coumarin-3-carboxylic acid ethyl esters (Scheme 2) were prepared by Knoevenagel reaction. To a mixture of diethyl malonate (1 mmol) and the appropriate salicylaldehyde (1 mmol) in ethanol (10 ml) was added piperidine (5 mol %) and the reaction mixture was stirred at the room temperature. The progress of the reaction was monitored by TLC. After completion of the reaction, the solvent was removed under vacuum and the residue was purified by chromatography. The obtained substituted coumarin-3-carboxylic acid ethyl ester (2 mmol) was dissolved in 10% NaOH (50 ml), then 3 N HCl (50 ml) was added the mixture. The suspension was filtered and dried under vacuum to provide substituted coumarin-3-carboxylic acid. The coumarin-3-carboxylic acid (2 mmol) was added to thionyl chloride (30 ml), the reaction mixture was refluxed for about 2 h, the thionyl chloride was removed under vacuum. The desired substituted coumarin-3-carbonyl chloride was obtained. To a mixture of substituted coumarin-3-carbonyl chloride (2 mmol) and toluene (20 ml) or ethyl ether (20 ml) was added dropwise appropriate alcohol (2 mmol) and then the reaction mixture was refluxed for about 12 h. The solvent was removed under vacuum and the residue was purified by chromatography.
65%	With hydrogenchloride In ethanol for 8h; Heating;
61%	With ethanol; sodium hydroxide for 1h; Reflux;
50%	With hydrogenchloride In ethanol for 8h; Heating;
	With sodium hydroxide
	With hydrogenchloride In ethanol for 3h; Heating;
	With sodium hydroxide; lithium hydroxide monohydrate In ethanol Heating;
	With sodium hydroxide
	With hydrogenchloride; lithium hydroxide monohydrate; sodium hydroxide
	With sodium hydroxide In lithium hydroxide monohydrate at 20℃;
	With sodium hydroxide for 3h; Reflux;
	With lithium hydroxide monohydrate; sodium hydroxide In ethanol at 20℃;
	With sodium hydroxide for 0.25h; Reflux;
	Stage #1: 2-oxo-2H-1-benzopyran-3-carboxylic acid ethyl ester With sodium hydroxide In ethanol; lithium hydroxide monohydrate for 0.25h; Reflux; Stage #2: With hydrogenchloride In ethanol; lithium hydroxide monohydrate	Preparation of coumarin-3-carboxylic acid (3) The mixture of coumarin-3-carboxylic acid ethyl ester 2 (4 g), NaOH (3 g), EtOH (15 mL) and water (10 mL) was refluxed for 15 min. After cooling, the reaction mixture was added to a solution of 10 mL concentrated hydrochloric acid in 50 mL water under stirring. Then the raw product was obtained by filtration and washed with ice water. Finally, the raw product was purified by recrystallized from 50% EtOH to give compound 3 as a white crystals
	Stage #1: 2-oxo-2H-1-benzopyran-3-carboxylic acid ethyl ester With sodium hydroxide at 90℃; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate
	With sodium hydroxide at 20℃;	5.3. General procedure for the synthesis of compounds 3a-o General procedure: NaOH solution (2N, 25 ml) was added to the ester derivatives 2a-o, and the mixture was stirred at room temperature for 5-7 h. After cooling, hydrochloric acid (2N) was added to the yellow solution until a white precipitate formed. The precipitated solid was isolated by filtration, washed with water and dried to give compounds 3a-o.
	With sodium hydroxide In lithium hydroxide monohydrate at 20℃;	4.4 General procedure for the synthesis of 2-oxo-2H-chromene-3-carboxylic acids (4a-u) General procedure: Esters (3a-v) were dissolved in aqueous sodium hydroxide (2N, 20mL) and were stirred at rt for 5-7h. After cooling, solution was acidified with hydrochloric acid (2N) until a white precipitate formed. The white solid was filtrated, washed with water and dried to yield acids (4a-u).
	With sodium hydroxide In ethanol; lithium hydroxide monohydrate
	Multi-step reaction with 2 steps 1: sodium hydroxide; lithium hydroxide monohydrate / ethanol / 0.33 h / Reflux 2: hydrogenchloride / ethanol; lithium hydroxide monohydrate
	With sodium hydroxide In lithium hydroxide monohydrate for 2h; Reflux;	Synthesis of 2-oxo-2H-chromene-3-carbonyl chloride General procedure: First, 5 mmol of salicylaldehyde (compound 1) dissolved in 10 ml dry ethanol. Next, 5 mmol of diethyl malonate (compound 2), 0.005 ml of glacial acetic acid and 0.05 ml of piperidine were added to the reaction mixture. This mixture was then refluxed for 6 h (monitored by TLC), and the resulting white precipitate was filtered and washed with cold ethanol several times, before being dried at ambient temperature to obtain compound 3. Next, this white precipitate was dissolved in 100 ml of 0.5% NaOH and refluxed for 2 h, until a clear solution was achieved. This solution was next acidified with HCl to reach a pH of 2, and cooled to 0 °C. In this way, a white precipitate was obtained, which was filtered and washed with cold ethanol, allowed to dry in ambient conditions and crystalized from ethanol (compound 4) (6.58 g, 82.2% yield) [29]. At last, to 2.5 mL of thionyl chloride in toluene was added 0.18 g of compound 4 (1 mmol) and the resulting mixture was refluxed at 80 °C for 6 h. Before the reaction was finished, the solvent of the reaction mixture was evaporated to finally collect 2-oxo-2H-chromene-3-carbonyl chloride (compound 5) without any further treatments.
	With sodium hydroxide In ethanol Reflux;
	With sodium hydroxide In ethanol
	With sodium hydroxide In ethanol for 0.25h; Reflux;	4.1.9. General procedures for the preparation of compounds 14a-g and16a-r General procedure: To a solution of 13a-g or 15a-r (10 mmol) in EtOH (15 mL) wasadded 15 mL of 10% NaOH and heated under reflux for 15 min.Acidification to pH 2 using concentrated hydrochloric acid and coolingto 0 °C gave a deposit. The solid was filtrated, washed with water anddried to yield acids 14a-g and 16a-r.
	With sodium hydroxide In ethanol at 95℃; for 2h;	4.3.3. General Procedures for the Preparation of Coumarin Derivatives 4a~4g General procedure: To a solution of intermediate 3a~3g in EtOH (20 mL), 10% NaOH (20 mL) was added.The reaction system was stirred at 95 C for 2 h, then cooled at room temperature andadjusted to be acidic (pH = 2) with HCl solution. Recrystallisation from the mixture solution(still standing at 0 C) obtained crud solid of coumarin derivatives. The crud solid waswashed with cooled H2O, and concentrated in vacuo to obtain white solid.2-oxo-2H-chromene-3-carboxylic acid (4a): White solid; yield 54%. 1H NMR (500 MHz,DMSO) 13.30 (s, 1H), 8.75 (s, 1H), 7.91 (dd, J = 7.7, 1.5 Hz, 1H), 7.74 (m, 1H), 7.42 (s, 2H).
	With lithium hydroxide monohydrate; sodium hydroxide In ethanol for 0.5h; Reflux;

Reference： [1]Current Patent Assignee: He Liqin; Zhang Zhuo; Wang Rong; Bai Zhiwei - CN106946868, 2017, A Location in patent: Paragraph 0487; 0506; 0507; 0509
[2]Current Patent Assignee: YULIN UNIVERSITY - CN109988140, 2019, A Location in patent: Paragraph 0024; 0028; 0029; 0030; 0033; 0034; 0037
[3]Luo, Xue; He, Xu-Dong; Zhao, Yuan-Chao; Chen, Chong; Chen, Biao; Wu, Zhi-Bing; Wang, Pei-Yi [Journal of Heterocyclic Chemistry, 2017, vol. 54, # 5, p. 2650 - 2655]
[4]Zhou, Xiang; Wang, Xiao-Bing; Wang, Tao; Kong, Ling-Yi [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 17, p. 8011 - 8021]
[5]Current Patent Assignee: NORTHWEST A&F UNIVERSITY - CN107445933, 2021, B Location in patent: Paragraph 0039; 0044-0045
[6]Prashanth; Avin, B.R. Vijay; Thirusangu, Prabhu; Ranganatha, V. Lakshmi; Prabhakar; Sharath Chandra, J.N. Narendra; Khanum, Shaukath Ara [Biomedicine and Pharmacotherapy, 2019, vol. 112]
[7]Bodke, Yadav D.; Naik, Mamata Devendra; Revanasiddappa, B. C.; Vijay Kumar, M. [Synthetic Communications, 2020]
[8]Chen, Guo Feng; Zhang, Li Yan; Li, Hong Yang; Chen, Bao Hua [Research on Chemical Intermediates, 2015, vol. 41, # 7, p. 4273 - 4281]
[9]Islam, A. M.; Bedair, A. H.; Aly, F. M.; El-Sharief, A. M. Sh.; El-Masry, F. M. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1980, vol. 19, # 3, p. 224 - 226]
[10]Current Patent Assignee: DALIAN UNIVERSITY OF TECHNOLOGY - CN107698571, 2018, A Location in patent: Paragraph 0024; 0025; 0026; 0027
[11]Li, Wen-Bo; Qiao, Xue-Peng; Wang, Zi-Xiao; Wang, Shuai; Chen, Shi-Wu [Bioorganic Chemistry, 2020, vol. 105]
[12]Jadhav, Hemant R.; Jain, Priti; Wadhwa, Pankaj [Letters in drug design and discovery, 2020, vol. 17, # 4, p. 416 - 425]
[13]Liu, Jinbing; Wu, Fengyan; Chen, Lingjuan; Zhao, Liangzhong; Zhao, Zibing; Wang, Min; Lei, Sulan [Food Chemistry, 2012, vol. 135, # 4, p. 2872 - 2878]
[14]Bhalla; Hitkari; Gujrati; Bhalla; Shanker [European Journal of Medicinal Chemistry, 1994, vol. 29, # 9, p. 713 - 717]
[15]Mesiti, Francesco; Gaspar, Alexandra; Chavarria, Daniel; Maruca, Annalisa; Rocca, Roberta; Gil Martins, Eva; Barreiro, Sandra; Silva, Renata; Fernandes, Carlos; Gul, Sheraz; Keminer, Oliver; Alcaro, Stefano; Borges, Fernanda [Journal of Medicinal Chemistry, 2021, vol. 64, # 15, p. 11169 - 11182]
[16]Singh; Srivastava; Palit; Shanker [Arzneimittel-Forschung/Drug Research, 1992, vol. 42, # 8, p. 993 - 996]
[17]Current Patent Assignee: Knoevenagel - DE97734, 1800, C Knoevenagel [Chemische Berichte, 1898, vol. 31, p. 2593][Chemisches Zentralblatt, 1898, vol. 69, # II, p. 695]
[18]Frédérick, Raphaël; Robert, Séverine; Charlier, Caroline; De Ruyck, Jérôme; Wouters, Johan; Pirotte, Bernard; Masereel, Bernard; Pochet, Lionel [Journal of Medicinal Chemistry, 2005, vol. 48, # 24, p. 7592 - 7603]
[19]Zhang, Hui; Yu, Tianzhi; Zhao, Yuling; Fan, Duowang; Qian, Long; Yang, Changhui; Zhang, Kai [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2007, vol. 68, # 3, p. 725 - 727]
[20]Location in patent: experimental part Chimenti, Franco; Secci, Daniela; Bolasco, Adriana; Chimenti, Paola; Bizzarri, Bruna; Granese, Arianna; Carradori, Simone; Yáñez, Matilde; Orallo, Francisco; Ortuso, Francesco; Alcaro, Stefano [Journal of Medicinal Chemistry, 2009, vol. 52, # 7, p. 1935 - 1942]
[21]Location in patent: experimental part Chimenti, Franco; Bizzarri, Bruna; Bolasco, Adriana; Secci, Daniela; Chimenti, Paola; Granese, Arianna; Carradori, Simone; Rivanera, Daniela; Zicari, Alessandra; Scaltrito, M. Maddalena; Sisto, Francesca [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 16, p. 4922 - 4926]
[22]Asadipour, Ali; Alipour, Masoumeh; Jafari, Mona; Khoobi, Mehdi; Emami, Saeed; Nadri, Hamid; Sakhteman, Amirhossein; Moradi, Alireza; Sheibani, Vahid; Homayouni Moghadam, Farshad; Shafiee, Abbas; Foroumadi, Alireza [European Journal of Medicinal Chemistry, 2013, vol. 70, p. 623 - 630]
[23]He, Xu; Chen, Yan-Yan; Shi, Jing-Bo; Tang, Wen-Jiang; Pan, Zhi-Xiang; Dong, Zhi-Qiang; Song, Bao-An; Li, Jun; Liu, Xin-Hua [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 14, p. 3732 - 3738]
[24]Wang, Yubin; Liu, Haitao; Lu, Peng; Mao, Rui; Xue, Xiaojian; Fan, Chen; She, Jinxiong [Chemical Biology and Drug Design, 2015, vol. 86, # 4, p. 637 - 647]
[25]Li, Dawei; Bu, Yazhong; Zhang, Lining; Wang, Xing; Yang, Yanyu; Zhuang, Yaping; Yang, Fei; Shen, Hong; Wu, Decheng [Biomacromolecules, 2016, vol. 17, # 1, p. 291 - 300]
[26]Huang, Peng; Gao, Lei-Lei; Zhang, Zhuo; Liu, Jing-Ru; He, Li-Qin [Heterocycles, 2016, vol. 92, # 3, p. 511 - 520]
[27]Yao, Dahong; Wang, Jing; Wang, Guan; Jiang, Yingnan; Shang, Lei; Zhao, Yuqian; Huang, Jian; Yang, Shilin; Wang, Jinhui; Yu, Yamei [Bioorganic Chemistry, 2016, vol. 68, p. 112 - 123]
[28]Ghanei-Nasab, Samaneh; Khoobi, Mehdi; Hadizadeh, Farzin; Marjani, Azam; Moradi, Alireza; Nadri, Hamid; Emami, Saeed; Foroumadi, Alireza; Shafiee, Abbas [European Journal of Medicinal Chemistry, 2016, vol. 121, p. 40 - 46]
[29]Abdizadeh, Tooba; Kalani, Mohammad Reza; Abnous, Khalil; Tayarani-Najaran, Zahra; Khashyarmanesh, Bibi Zahra; Abdizadeh, Rahman; Ghodsi, Razieh; Hadizadeh, Farzin [European Journal of Medicinal Chemistry, 2017, vol. 132, p. 42 - 62]
[30]Chen, Guo Feng; Liu, Lin; Wu, Jiu Li; Wu, Suo Juan; Chen, Bao Hua [Research on Chemical Intermediates, 2018, vol. 44, # 2, p. 1381 - 1395]
[31]Zhang, Zhuo; Bai, Zhi-Wei; Ling, Yong; He, Li-Qin; Huang, Peng; Gu, Hong-Xia; Hu, Rong-Feng [Medicinal Chemistry Research, 2018, vol. 27, # 4, p. 1198 - 1205]
[32]Hosseini, Morteza; Khoobi, Mehdi; Tarasi, Roghayeh; Ganjali, Mohammad Reza [Research on Chemical Intermediates, 2018, vol. 44, # 9, p. 5031 - 5042]
[33]Jesumoroti, Omobolanle J.; Faridoon; Mnkandhla, Dumisani; Isaacs, Michelle; Hoppe, Heinrich C.; Klein, Rosalyn [MedChemComm, 2019, vol. 10, # 1, p. 80 - 88]
[34]Elias, Rebecca; Benhamou, Raphael I.; Jaber, Qais Z.; Dorot, Orly; Zada, Sivan Louzoun; Oved; Pichinuk, Edward; Fridman [European Journal of Medicinal Chemistry, 2019, vol. 179, p. 779 - 790]
[35]Bai, Renren; Gu, Jinping; Guo, Jianan; Jiang, Xiaoying; Lv, Yangjing; Mi, Zhisheng; Shi, Yuan; Xie, Yuanyuan; Yao, Chuansheng; Zhang, Changjun; Zhou, Tao [Bioorganic and medicinal chemistry, 2020, vol. 28, # 12]
[36]Lu, Tao; Nie, Xuliang; Peng, Dayong; Wang, Jie; Xiong, Wanming; Yin, Zhongping; Zeng, Fanxin [Molecules, 2022, vol. 27, # 7]
[37]Ślusarczyk, Lidia; Ciszkowicz, Ewa; Creaven, Bernadette; Jenkins, Hollie; Kamiński, Daniel; Karcz, Dariusz; Lecka-Szlachta, Katarzyna; Matwijczuk, Arkadiusz; Miłoś, Anna; Starzak, Karolina [International Journal of Molecular Sciences, 2022, vol. 23, # 11]

4
[ 141-82-2 ]
[ 90-02-8 ]
[ 531-81-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	With triton-B adsorbed on flyash In neat (no solvent) for 0.00972222h; Microwave irradiation; Green chemistry;
95%	With zirconyl chloride octahydrate; sodium amide In tetrahydrofuran at 25℃; for 0.5h; Green chemistry;	General procedure for the synthesis of chromen-2-one derivatives from salicylaldehydes and active methylene compounds (3a-m) General procedure: A mixture of salicylaldehyde (1, 1 mmol), active methylene compound (2, 1.2 mmol), ZrOCl2-THF (0.048 g, 0.15 mmol) and sodium amide (0.005 g, 0.15 mmol) was stirred for 30 min at room temperature. The progress of the reaction was monitored by TLC. After the completion of reaction, the crude mixture was diluted with moist ether (20 mL). The resultant reaction mixture was washed with water (3 × 25 mL) to discharge the colour, ZrOCl2 and sodium amide. The ethereal solution obtained after extraction was dried over anhydrous Na2SO4 and evaporated under reduced pressure. Finally, this reaction mixture was purified by passing through a silica gel column chromatography to get pure product (Scheme-I). Coumarin-3-carboxylic acid (3a): Colorless solid, m.p.: 189-191 °C; IR (KBr, νmax, cm-1): 3450 (-OH), 1676 (-C=O). 1H NMR (400 MHz, DMSO-d6): δ 8.74 (s,1H), 7.90 (d, 1H, J = 7.6 Hz), 7.73 (m, 1H), 7.44 (d, J = 8 Hz, 1H), 7.41 (t, J = 7.2 Hz, 1H). 13C NMR (100 MHz, DMSO-d6): δ 164.39, 157.13, 154.85, 148.75, 134.70, 130.59, 125.25, 118.74, 118.37, 116.53. Elemental analysis for C10H6O4: C, 63.14 (63.16); H, 3.16 (3.18).
90%	With aqueous extract of Acacia concinna; pods In water for 2h; Reflux; Green chemistry;	Synthesis of 3-carboxycoumarins Method II: A mixture of salicylaldehyde (1), malonic acid (4) and 5 mL of 20 % aqueous extract of Acacia concinna were heated under reflux for 2 h. The reaction mixture was allowed to cool to room temperature then it was poured off in ice cold water. Solid product was filtered off and the crude product was recrystallized by water to obtain pure coumarin-3-carboxylic acid (3) (Scheme-III).

89%	With <i>L</i>-proline In neat (no solvent) at 90℃; for 6h;	4.1.20 3-Carboxycoumarin 6 To the stirred reaction mixture of malonic acid (1mmol) and salicylaldehyde (1mmol), l-proline (10mol %) was added under neat conditions. The reaction mixture was heated at 90 °C for 6h and the completion of reaction was monitored by TLC. After completion of the reaction, the reaction mixture was cooled and solid obtained was recrystallized from ethanol. Yield: 89%, mp 189-191°C (lit [45]. 190-191°C); 1H NMR (CDCl3): 7.48 (s, 1H, H-4), 6.54 (d, J=8.0Hz, 1H, H-5), 6.45 (m, 1H, H-7), 6.13 (m, 2H, H-6 and H-8).
88%	With potassium phtalimide In water at 20℃; for 4h; Green chemistry;	General procedure for the PPI-promoted synthesis of title compounds (3, 4 and 6) General procedure: Salicylaldehyde derivative (1 mmol), active methylene compound (1 mmol) and PPI were added to 5 mL of water and the reaction mixture was stirred at room temperature for the appropriate time (Table 2). After completion of the reaction (as indicated by TLC analysis), the mixture was filtered to separate the precipitated product, which was further purified by rinsing with cold reaction solvent. The filtrate was charged with the same substrates and was reused for successive cycles. The products were identified by comparison with authentic samples or NMR data.
87%	With zinc(II) chloride In chloroform for 0.75h; Heating;
76%	With LEUCINE In neat (no solvent) at 100℃; for 2h;	Preparation of arylidene propanedioic acids General procedure: A mixture consisting of 0.2 mol of benzaldehyde (1), 0.2 mol of malonic acid (2) and 0.01 g of an amino acid in a 50 mL round bottomed flask was heated on a water bath for 2 h. The reaction mixture was cooled to room temperature and poured into 20 mL cold water. After 15 min standing it was filtered, washed with water, dried and recrystallized from ethanol to give benzylidenepropanedioic acid (3)
	With ethanol; aniline
	With acetic acid
	With ethanol; ammonia
	With acetic acid; aniline; Petroleum ether
	With piperidine; ethanol
	With ethanol; ammonia
	With ethanol; aniline
	With ethanol; aniline hydrochloride

Reference： [1]Goel, Vijender [Oriental Journal of Chemistry, 2012, vol. 28, # 4, p. 1725 - 1728]
[2]TASQEERUDDIN; ASIRI, YAHYA I.; SHAHEEN [Asian Journal of Chemistry, 2020, vol. 32, # 10, p. 2611 - 2616]
[3]Shafqat, Syed Salman; Khan, Amir Azam; Khan, Misbahul Ain; Salleh, Shanti Faridah; Jamaludin, Mohd Syahmi; Cem, Pang Suh [Asian Journal of Chemistry, 2017, vol. 29, # 2, p. 261 - 266]
[4]Butcher, R. J.; Katiyar, Diksha; Sharma, Rajesh Kumar; Singh, Vineeta; Tiwari, Neha [Bioorganic Chemistry, 2020, vol. 98]
[5]Kiyani, Hamzeh; Daroonkala, Masoumeh Darzi [Bulletin of the Chemical Society of Ethiopia, 2015, vol. 29, # 3, p. 449 - 456]
[6]Srinivas, K.; Krishna, K. L.; Sivaprasad, A.; Rao, P. Shanthan [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1998, vol. 37, # 9, p. 936 - 938]
[7]Shafqat, Syed Salman; Khan, Misbahul Ain; Zulkharnain, Azham; Hamdan, Sinin; Henry Rigit, Andrew Ragai; Khan, Amir Azam [Asian Journal of Chemistry, 2014, vol. 26, # 24, p. 8463 - 8466]
[8]Knoevenagel [Chemische Berichte, 1898, vol. 31, p. 2619][Chemisches Zentralblatt, 1898, vol. 69, # II, p. 695]
[9]Stuart [Journal of the Chemical Society, 1886, vol. 49, p. 366]
[10]Knoevenagel [Chemische Berichte, 1898, vol. 31, p. 2619][Chemisches Zentralblatt, 1898, vol. 69, # II, p. 695]
[11]Current Patent Assignee: DOW INC - US2338569, 1941, A
[12]Current Patent Assignee: Knoevenagel - DE164296, 1800, C
[13]Current Patent Assignee: Knoevenagel - DE97735, 1800, C
[14]Current Patent Assignee: Knoevenagel - DE97735, 1800, C
[15]Current Patent Assignee: Knoevenagel - DE161171, 1800, C

5
[ 527-62-8 ]
[ 531-81-7 ]
[ 71860-21-4 ]

Reference： [1]Journal of the Indian Chemical Society,1979,vol. 56,p. 505 - 507

6
[ 531-81-7 ]
[ 38191-33-2 ]
[ 71860-20-3 ]

Reference： [1]Journal of the Indian Chemical Society,1979,vol. 56,p. 505 - 507

7
[ 531-81-7 ]
[ 343269-52-3 ]
[ 71860-25-8 ]

Reference： [1]Journal of the Indian Chemical Society,1979,vol. 56,p. 505 - 507

8
[ 531-81-7 ]
[ 17672-22-9 ]
[ 71860-18-9 ]

Reference： [1]Journal of the Indian Chemical Society,1979,vol. 56,p. 505 - 507

9
[ 531-81-7 ]
[ 62-53-3 ]
[ 54396-25-7 ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Stage #2: aniline With triethylamine In dichloromethane at 20℃; for 12h;	4.1.3. Synthesis of 2-Oxo-N-substituted phenyl-2H-chromene-3-carboxamide (13a-13r) General procedure: To the coumarin-3-carboxylic acid (1.0 g) in 20 ml dry DCM was added EDCl-HCl (0.6 g), and HOBt (0.55 g). After stirring at RT for 30 min, the amine (1.1 equiv) was added followed by triethylamine (1 ml). The reaction mixture was stirred at RT for 12 h. The progress of the reaction was monitored by using TLC (ethyl acetate/n-hexane: 30:70). After completion of the reaction, the reaction mixture was diluted with DCM and washed with 1M HCl solution. The organic layer was separated and further treated with saturated sodium bicarbonate solution followed by brine solution. The organic layer was dried on sodium sulfate and concentrated by using rota-evaporator. The crude product was recrystallized in Dichloromethane: Pentane (2:8). 4.1.3.1. 2-Oxo-N-phenyl-2H-chromene-3-carboxamide (13a): Yellow solid; yield 72% Mp 182-184 °C, 1H-NMR (400 MHz, CDCl3): δ 7.38-7.76 (m, 9H, ArH), 9.06 (s, 1H, -C=H), 10.9 (s, 1H, CO-NH); 13C NMR (100 MHz, CDCl3): δ 113.3, 115.2, 116.2, 118.4, 120.3, 120.9, 123.2, 124.4, 126.1 128.8, 128.8, 130.3, 134.4, 146.6, 153.5, 160.5 ppm; IR (KBr): νmax 3387, 3104, 2965, 2864, 1745, 1642, 1549 cm-1; EI-MS (m/z): 266.18 (M+H)+.
71%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: aniline In dichloromethane at 26 - 28℃; for 4h; Inert atmosphere;
65%	With dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;

With propyl phosphoric acid anhydride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0℃; for 0.666667h;

2 2.1.1 General procedure for the preparation of compounds 3a-3f, 3j-3q (Scheme 1) General procedure: To compound 2 (5.0mmol, 0.95g) dissolved in dry DMF (30mL) aniline (6.0mmol, 1mL) was added and the mixture was stirred at iced water. Once 2 was completely dissolved, DIEA (15.0mmol, 1.94g) and T3P (propyl phosphoric acid anhydride, 5.5mmol, 1.75g) were added gradually with stirring and cooling for 40min. After mixed with the appropriate water, the solution was extracted with ethyl acetate, and then washed with water for three times, and the product was purified by column chromatography to give a white solid.

Reference： [1]Jadhav, Hemant R.; Jain, Priti; Wadhwa, Pankaj [Letters in drug design and discovery, 2020, vol. 17, # 4, p. 416 - 425]
[2]Khullar, Sadhika; Mandal, Sanjay K.; Markad, Datta [Inorganic Chemistry, 2020]
[3]Singh; Srivastava; Palit; Shanker [Arzneimittel-Forschung/Drug Research, 1992, vol. 42, # 8, p. 993 - 996]
[4]Yu, Xiang; Teng, Peng; Zhang, Ya-Ling; Xu, Zhao-Jun; Zhang, Ming-Zhi; Zhang, Wei-Hua [Fitoterapia, 2018, vol. 127, p. 387 - 395]

10
[ 531-81-7 ]
[ 625-56-9 ]
2-Oxo-2H-chromene-3-carboxylic acid acetoxymethyl ester [ No CAS ]

Reference： [1]Russian Journal of Bioorganic Chemistry,1997,vol. 23,p. 288 - 291
Bioorganicheskaya Khimiya,1997,vol. 23,p. 310 - 313

11
[ 531-81-7 ]
[ 57260-73-8 ]
[ 287401-64-3 ]

Yield	Reaction Conditions	Operation in experiment
94%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine In acetonitrile at 20℃; for 10h;
74%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With 4-methyl-morpholine; 2-chloro-4,6-dimethoxytriazine In acetonitrile at 0℃; for 2h; Stage #2: N-BOC-1,2-diaminoethane In acetonitrile at 0 - 20℃;
38%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 24h;	15 Coumarin 3-carboxylate (0.762 g, 4 mmol),HOBt (1.62 g, 12 mmol),EDC · HCl (2.30 g, 12 mmol) were mixed,Add DCM (40ml) and dissolve well before addingMono Boc-ethylenediamine (0.769 g, 4.8 mmol),Finally Et3N (1.21 g, 12 mmol),Continue stirring at room temperature for 24h.The reaction was quenched with the appropriate amount of water and extracted with DCM and water to removeWater soluble salt, separated organic phase, dried over anhydrous Na2SO4. After the solvent was removed by rotary evaporation under reduced pressure, 10 ml of CH2Cl2 and 3 g of 60-100 mesh silica gel, mix well spin dry. Flash column chromatography using ethyl acetate / petroleum ether = 1/4 as eluent gave Compound 23 (whiteColor solid, 38% yield).

With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate In acetonitrile at 20℃;

3.2. General Synthetic Method for the Preparation of 2a-e General procedure: Coumarin derivatives 2a-e were synthesised by the adaptation of a previously reported procedurewith an additional step of deprotection for Boc-2e [20]. Coumarin-3-carboxylic acid (1 eq.), a selectedamine (1.1 eq.), and PyBOP (1 eq.) were stirred at room temperature in acetonitrile. Upon completion,the reaction was quenched with brine (30 mL/5 mmol of coumarin-3-carboxylic acid) and extractionwas conducted with dichloromethane (30 mL/5 mmol of coumarin-3-carboxylic acid). The organic layerwas then washed with 10% citric acid, then 10% NaHCO3, following water and brine. The organicresidues were dried over Na2SO4. Finally, the solvent was removed under vacuum. The residues weretriturated with ethyl acetate to give the desired product as a solid.

Reference： [1]Roy, Bidhan C.; Peterson, Rachel; Mallik, Sanku; Campiglia, Andres D. [Journal of Organic Chemistry, 2000, vol. 65, # 12, p. 3644 - 3651]
[2]Brinas, Raymond P.; Troxler, Thomas; Hochstrasser, Robin M.; Vinogradov, Sergei A. [Journal of the American Chemical Society, 2005, vol. 127, # 33, p. 11851 - 11862]
[3]Current Patent Assignee: SHANGHAITECH UNIVERSITY - CN107400072, 2017, A Location in patent: Paragraph 0037; 0128; 0129
[4]Bao, Lei; Cole, Ivan S.; Lan, Minbo; Qian, Bin; Reichman, Suzie M.; Trinchi, Adrian; Váradi, Linda; Wei, Gang [Molecules, 2019, vol. 24, # 19]

12
[ 531-81-7 ]
[ 939-18-4 ]

Reference： [1]Journal of Chemical Research,2005,p. 617 - 619
[2]RSC Advances,2019,vol. 10,p. 482 - 491
[3]Tetrahedron Letters,2001,vol. 42,p. 1065 - 1067

13
[ 531-81-7 ]
[ 44520-55-0 ]
[ 672291-96-2 ]

Reference： [1]Chemistry - A European Journal,2004,vol. 10,p. 173 - 181

14
[ 531-81-7 ]
[ 13052-92-1 ]
2-(2'-oxo-2'H-chromen-3'-yl)-benzoxazole-5-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Journal of Chemical Research,2004,p. 120 - 122

15
[ 959-36-4 ]
[ 531-81-7 ]

Reference： [1]Journal of Heterocyclic Chemistry,1985,vol. 22,p. 463 - 464

16
[ 79-37-8 ]
[ 531-81-7 ]
[ 34805-17-9 ]
[ 196808-22-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; N,N-dimethyl-formamide;	Example 10 3-(4-Benzyloxy-phenyl)-2(S)-[(4-oxo-4H-chromene-3-carbonyl)-amino]-propionic acid methyl ester To a stirring solution of 360 mg (2 mmol) of chromone-3-carboxylic acid in 25 mL of CH2Cl2 at 0 C. were added several drops of DMF followed by 1 mL of 2M solution of oxalyl chloride in CH2Cl2. The resulting solution was stirred 3 h at rt and 643 mg (2 mmol) of <strong>[34805-17-9]O-benzyl-L-tyrosine methyl ester hydrochloride</strong> and 0.2 g (2.0 mmol) of triethylamine in 15 mL of CH2Cl2 were added and stirring continued overnight. Solvent was removed under reduced pressure. Product was purified by LCC on SiO2 (Hexane: EtOAc 13:7) providing 83 mg of title compound as a white solid: low resolution MS (ES+ (M+H), 458; RP-HPLC (Dynamax C-8 25 cm*4.1 mm; 50-90% CH3CN in H2O with 0.1% TFA buffer; 15 minutes; 2 mL/min): tr=10.44 min.

Reference： [1]Patent: US6294580,2001,B1

17
[ 531-81-7 ]
[ 123-30-8 ]
[ 1846-97-5 ]

Yield	Reaction Conditions	Operation in experiment
74%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 24h;
72%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h;	2.1. Synthesis of CA-OH compound Coumarin-6-carboxylic acid (0.95 g, 5.0 mmol), 4-dimethylaminopyridine(DMAP, 0.67 g, 5.5 mmol), and 1-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 1.1 g, 5.5 mmol) were dissolvedin 30 mL of dichloromethane. Dichloromethane mixture of 4-aminophenol (0.57 g, 5.1 mmol) was then added with a dropper andstirred at room temperature for 24 h. The rude product was filtered andpurified by recrystallization (ethanol/water, v/v, 8/2) to obtain 1.1 g ofyellow solid CA-OH compound with 72% yield. 1H NMR (600 MHz,DMSO-d6) 10.45 (s, 1H), 9.35 (s, 1H), 9.35 (s, 1H), 8.90 (s, 1H), 8.01(d, J = 7.8 Hz, 1H), 7.77 (t, J = 7.8 Hz, 1H), 7.55-7.51 (m, 3H), 7.47 (t,J = 7.8 Hz, 1H), 6.77 (d, J = 8.4 Hz, 2H). 13C NMR (151 MHz, DMSO-d6) 161.05, 159.59, 154.76, 154.32, 147.58, 134.59, 130.70, 130.02,125.72, 122.08, 120.42, 119.03, 116.68, 115.87. HRMS (m/z): calcd forC22H12N4O7: 445.0779; found: 445.0795 [M+ H]+.
61%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Stage #2: 4-amino-phenol With triethylamine In dichloromethane at 20℃; for 12h;	4.1.3. Synthesis of 2-Oxo-N-substituted phenyl-2H-chromene-3-carboxamide (13a-13r) General procedure: To the coumarin-3-carboxylic acid (1.0 g) in 20 ml dry DCM was added EDCl-HCl (0.6 g), and HOBt (0.55 g). After stirring at RT for 30 min, the amine (1.1 equiv) was added followed by triethylamine (1 ml). The reaction mixture was stirred at RT for 12 h. The progress of the reaction was monitored by using TLC (ethyl acetate/n-hexane: 30:70). After completion of the reaction, the reaction mixture was diluted with DCM and washed with 1M HCl solution. The organic layer was separated and further treated with saturated sodium bicarbonate solution followed by brine solution. The organic layer was dried on sodium sulfate and concentrated by using rota-evaporator. The crude product was recrystallized in Dichloromethane: Pentane (2:8).

42%

Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: 4-amino-phenol In dichloromethane at 20℃; for 4h; Inert atmosphere;

Reference： [1]Le Bras, Gaëlle; Radanyi, Christine; Peyrat, Jean-François; Brion, Jean-Daniel; Alami, Mouâd; Marsaud, Véronique; Stella, Barbara; Renoir, Jack-Michel [Journal of Medicinal Chemistry, 2007, vol. 50, # 24, p. 6189 - 6200]
[2]Fan, Yu Zhu; Han, Lei; Li, Nian Bing; Luo, Hong Qun; Qing, Min; Xu, Zi Yi; Yang, Yu Zhu [Dyes and Pigments, 2021, vol. 184]
[3]Jadhav, Hemant R.; Jain, Priti; Wadhwa, Pankaj [Letters in drug design and discovery, 2020, vol. 17, # 4, p. 416 - 425]
[4]Fonseca, André; Matos, Maria João; Vilar, Santiago; Kachler, Sonja; Klotz, Karl-Norbert; Uriarte, Eugenio; Borges, Fernanda [Chemical Biology and Drug Design, 2018, vol. 91, # 1, p. 245 - 256]

18
[ 10025-74-8 ]
[ 531-81-7 ]
Dy(cca)2Cl*H₂O [ No CAS ]

Reference： [1]Inorganica Chimica Acta,1989,vol. 159,p. 157 - 162

19
[ 10025-74-8 ]
[ 531-81-7 ]
Dy(cca)Cl₂*0.5n-BuOH [ No CAS ]

Reference： [1]Inorganica Chimica Acta,1989,vol. 159,p. 157 - 162

20
[ 95-14-7 ]
[ 531-81-7 ]
[ 312929-01-4 ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: 1,2,3-Benzotriazole With thionyl chloride In tetrahydrofuran at 20℃; for 0.333333h; Stage #2: 2-oxo-2H-chromene-3-carboxylic acid In tetrahydrofuran at 25℃; for 4h;
87%	Stage #1: 1,2,3-Benzotriazole With thionyl chloride In tetrahydrofuran at 20℃; for 0.333333h; Stage #2: 2-oxo-2H-chromene-3-carboxylic acid In tetrahydrofuran at 25℃; for 4h;
82%	Stage #1: 1,2,3-Benzotriazole With thionyl chloride In tetrahydrofuran at 20℃; for 0.333333h; Stage #2: 2-oxo-2H-chromene-3-carboxylic acid In tetrahydrofuran at 25℃;

76%	With thionyl chloride In dichloromethane
76%	With thionyl chloride In dichloromethane at 20℃; for 12h;
73%	Stage #1: 1,2,3-Benzotriazole With thionyl chloride In dichloromethane at 20℃; for 0.5h; Stage #2: 2-oxo-2H-chromene-3-carboxylic acid In dichloromethane at 20℃; for 12h;	Synthesis of compounds 7a,b General procedure: Thionyl chloride (1.78 g,0.015 mol) was added to a solution of 1H-benzotriazole (5.95 g, 0.05 mol) in CH2Cl2 (75 ml). The mixture was stirred for 30 min at room temperature. Then the corresponding coumarin-3-carboxylic acid 6a,b (0.01 mol) was added and the reaction mixture was stirred for 12 h at room temperature. The precipitate was removed by filtration,and the filtrate was evaporated under reduced pressure. The residue was diluted with CH2Cl2 (100 ml),and the solution was washed with 10% Na2CO3 solution(50 ml) and 4 N HCl (50 ml) and dried over MgSO4. Removal of the solvent under reduced pressure gave compounds 7a,b, which were recrystallized from CH2Cl2-hexane, 1:1.
73%	Stage #1: 1,2,3-Benzotriazole With thionyl chloride In dichloromethane at 20℃; for 0.5h; Stage #2: 2-oxo-2H-chromene-3-carboxylic acid In dichloromethane at 20℃; for 12h;	Synthesis of compounds 8a-f and 9; general procedure General procedure: Thionyl chloride (1.78 g, 0.015 mol) was added to a solution of1H-benzotriazole (5.95 g, 0.05 mol) in CH2Cl2 (75 mL). The mixturewas stirred for 30 min at room temperature. Then the correspondingcoumarin-3-carboxylic acid (6a-f and 7) (0.01 mol) was added and the reaction mixture was stirred for 12 h at room temperature. The precipitate was removed by filtration, and the filtrate was evaporated under reduced pressure. The residue was diluted with CH2Cl2(100 mL), and the solution was washed with 10 % Na2CO3 solution(50 mL) and 4 N HCl (50 mL) and dried over MgSO4. Removal of the solvent under reduced pressure gave compounds 8a-f and 9, whichwere recrystallised from CH2Cl2-hexane, 1:1. 3-(1H-Benzotriazol-1-ylcarbonyl)-2H-chromen-2-one (8a): White solid; yield 2.12 g (73%); m.p. 179-180 °C (lit.10 176-177 °C).
73%	With thionyl chloride In dichloromethane
73%	With sulfuryl dichloride In dichloromethane
	With thionyl chloride In dichloromethane
	With thionyl chloride In dichloromethane at 20℃;
	With thionyl chloride In dichloromethane

Reference： [1]Location in patent: experimental part Katritzky, Alan R.; Narindoshvili, Tamari; Angrish, Parul [Synthesis, 2008, # 13, p. 2013 - 2022]
[2]Location in patent: experimental part Katritzky, Alan R.; Ibrahim, Tarek S.; Tala, Srinivasa R.; Abo-Dya, Nader E.; Abdel-Samii, Zakaria K.; El-Feky, Said A. [Synthesis, 2011, # 9, p. 1494 - 1500]
[3]Location in patent: experimental part Katritzky, Alan R.; Abdelmajeid, Abdelmotaal; Tala, Srinivasa R.; Amine; Steel, Peter J. [Synthesis, 2011, # 1, p. 83 - 90]
[4]Menteşe, Emre; Yilmaz, Fatih; Mutlu, Fatih; Kahveci, Bahittin [Journal of Chemical Research, 2015, vol. 39, # 11, p. 645 - 648]
[5]Menteşe, Emre; Karaali, Nesrin; Akyüz, Gülay; Yılmaz, Fatih; Ülker, Serdar; Kahveci, Bahittin [Chemistry of Heterocyclic Compounds, 2016, vol. 52, # 12, p. 1017 - 1024][Khim. Geterotsikl. Soedin., 2016, vol. 52, # 12, p. 1017 - 1024]
[6]Kahveci, Bahittin; Yilmaz, Fatih; Menteşe, Emre; Ülker, Serdar [Chemistry of Heterocyclic Compounds, 2015, vol. 51, # 5, p. 447 - 456][Khim. Geterotsikl. Soedin., 2015, vol. 51, # 5, p. 447 - 456,10]
[7]Yilmaz, Fatih [Journal of Chemical Research, 2018, vol. 42, # 7, p. 361 - 365]
[8]Fatih Yılmaz; Menteşe, Emre; Baltaş, Nimet [Russian Journal of Bioorganic Chemistry, 2019, vol. 45, # 6, p. 575 - 584][Bioorg. Khim., 2019, vol. 45, # 6, p. 575 - 584,10]
[9]Yilmaz, Fatih; Menteşe, Emre; Sökmen, Bahar Bilgin [Journal of Heterocyclic Chemistry, 2021, vol. 58, # 1, p. 260 - 269]
[10]Biswas, Suvendu; Avan, Ilker; Basak, Akash K.; Abo-Dya, Nader E.; Asiri, Abdullah; Katritzky, Alan R. [Amino Acids, 2013, vol. 45, # 1, p. 159 - 170] Yilmaz, Fatih; Menteşe, Emre [Journal of Chemical Research, 2017, vol. 41, # 1, p. 4 - 6]
[11]Yilmaz, Fatih; Menteşe, Meltem [Revue Roumaine de Chimie, 2017, vol. 62, # 12, p. 941 - 946]
[12]Menteşe, Emre; Akyüz, Gülay; Yılmaz, Fatih; Baltaş, Nimet; Emirik, Mustafa [Archiv der Pharmazie, 2018, vol. 351, # 12]

21
[ 531-81-7 ]
[ 64-04-0 ]
2-oxo-2H-1-benzopyran-3-N-(2-phenylethyl)carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With dmap; N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 50℃; for 8h;	General procedure B for the synthesis of coumarin-3-acylamino derivative General procedure: To a solution of coumarin-3-carboxyl acid derivatives 2 (1 mM) in dry N,N-dimethylformamide (DMF) was added dicyclohexylcarbodiimide (DCC, 1.1 mM) as the dehydrant and N,N-dimethylaminopyridine (DMAP, 5 mg) as the catalyst. The mixture was added N,N-diisopropylethylamine (DIPEA, 0.5 mM) and phenethylamine or tyramine (1.1 mM) after stirred for 10 min, then heated at 50 °C for 8 h. After the reaction mixture was cooled, the precipitates were filtrated, the solution was extracted by CH3COOC2H5 and water, combined organic layers and dried over Na2SO4 and evaporated to afford crude compound 3. The crude product 3 was further purified by flash column chromatography with corresponding eluent.
68%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Stage #2: phenethylamine In dichloromethane at 20℃; for 12h;

Reference： [1]Yang, Yang; Liu, Qing-Wen; Shi, Ye; Song, Zhi-Guang; Jin, Ying-Hua; Liu, Zai-Qun [European Journal of Medicinal Chemistry, 2014, vol. 84, p. 1 - 7]
[2]Location in patent: experimental part Das, Asish R.; Medda, Arunima; Singha, Raghunath; Samanta, Anuva; Guchhait, Nikhil [Journal of the Indian Chemical Society, 2008, vol. 85, # 11, p. 1124 - 1129]

22
[ 531-81-7 ]
[ 75-31-0 ]
[ 158577-01-6 ]

Reference： [1]Synthetic Communications,2010,vol. 40,p. 3281 - 3289

23
[ 531-81-7 ]
[ 665-66-7 ]
[ 302952-33-6 ]

Yield	Reaction Conditions	Operation in experiment
50%		One portion of N,N-carbonyldiimidazole (0.33 g, 2.035 mmol) was added to a solution of coumarin-3-carboxylic acid (0.352 g, 1.85 mmol) in DMF (10 mL). The resulting solution was stirred at 60 C for 24 hrs, after which a solution of <strong>[665-66-7]amantadine hydrochloride</strong> (0.28 g, 1.85 mmol), in DMF (5 mL) and triethylamine (0.77 mL) was added. The resulting solution was stirred for 24 hrs under reflux conditions. The crude product was added to DCM, extracted from water acidified with 32% HCl to pH 3. The water phase was basified with 1 N NaOH (pH 12) and extracted with DCM (2 × 25 mL). The combined organic layers were removed in vacuo rendering the crude product as a white solid. The solid was recrystallized from ethanol, rendering the pure product as a white crystalline solid (0.300 g, 0.93 mmol, 50%).Physical data: C20H21NO3; mp: 300 C; 1H NMR (600 MHz, CDCl3) deltaH: 8.90 (s, 1H,), 7.71-7.62 (m, 2H), 7.41-7.33 (m, 2H), 2.05 (s, 3H), 1.75-1.64 (m, 12H); 13C NMR (150 MHz, CDCl3) deltaC: 161.60, 159.89, 154.30, 147.64, 133.69, 129.64, 125.13, 119.53, 118.72, 116.48, 52.28, 41.35, 36.34, 30.88, 29.39. APCI-MS (300 C, 70 eV) m/z: 324.16 (M+); HREI-MS: Calcd for C20H21NO3 (MH+); 323.15159, found 323.15214. IR (ATR) numax: 3341, 2911, 2853, 1609, 1503, 1365, 754.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 3935 - 3944

24
[ 531-81-7 ]
[ 779-27-1 ]

Yield	Reaction Conditions	Operation in experiment
	With gold; superoxide dismutase; In dimethyl sulfoxide;Irradiation; Enzymatic reaction;Kinetics; Catalytic behavior;	[0050] 2. Experimental Protocol [0051] 2.1. Preparation of 3-coumarin-carboxyIic acid (3-CCA) solution [0052] A 20 mM 3-CCA (Sigma-Aldrich, 99%) solution dissolved in 80 mM equimolar phosphate buffer in 10 mL of Millipore water was gently heated and stirred in a sealed flask until dissolution. After cooling, an addition of 14 i of DMSO yielded a 20 mM 3-CCA/l OO mM DMSO solution. The solution was diluted 10 times with 80 mM phosphate buffer to produce a stock solution of 2 mM CCA/ 10 mM DMSO. [0053] 2.2. Preparation of Samples for Radiation Experiments [0054] In a cell culture plate (Falcon, 24 wells), equal volume of water and the previously prepared stock solution were mixed together to result in a 300 LL of a 1 mM 3- CCA/5 mM DMSO sample. Similarly, an AuNP solution was mixed with the 3-CCA solution in an identical fashion. Both samples were placed in a BD Falcon 24-well Multiwell plate and placed in a HP Faxitron Model 4385SA to irradiate for 30 minutes at 100 kVp at the dose rate of 3.3 Gy/min. The dose rate was calibrated using Fricke dosimeter.1 1 For dose rates from 6-40 Gy/min, the sample was irradiated for a total of 100 Gy using a microfocus X-ray source (L9631 , Hamamatzu). [0055] 2.3 Treatment of Samples after Irradiation [0056] Afterwards, the solution was diluted until the absorbance of the AuNPs no longer caused fuorometric interference. In the case where the concentration of gold was too high to obtain a reasonable signal-to-noise ratio, the solution was filtered by centrifugation at 6000 rpm for 15 minutes (Amicon Ultra- 15 Centrifugal Filter Unit, 10,000 MWCO). [0057] 2.4. Fluorometric Analysis [0058] The resulting solution was subjected to quantitative fluorometric analysis at an excitation wavelength of 395 nm and emission wavelength of 442 nm (FluoroMax-P, HORIBA Jobin Yvon). A calibration was performed to correct for the difference in dosage among the wells. The yield of 7-hydroxy-coumarin-3-carboxylic acid (7-OH-CCA) was determined by comparison with a calibration curve determined by commercial 7-OH-CCA (Anaspec). The method of studying of 3-CCA conversion to 7-OH-CCA under X-ray radiation adopted here was similar to those previously published.12' 13 [0059] 2.5. Superoxide Dismutase (SOD) [0060] Superoxide dismutase (Sigma-Aldrich, Specification) was weighed and dissolved in water to make stock solutions. A calculated volume of the stock solutions is then mixed with pre-made 3-CCA/DMSO stock solution to result in 300 xL of a 0.01 -0.5 mg/mL superoxide dismutase/1 mM 3-CCA/5 mM DMSO solution. Using the same technique, an identical volume of Millipore water was added to another aliquot of the stock CCA/DMSO solution to make a control sample. The two samples were subjected to radiation at 3.3 Gy/min and then measured using fluorometry as described earlier.
	With iron(II) ethylenediaminetetraacetic acid; dihydrogen peroxide; In aq. buffer;pH 9.0;Irradiation;Kinetics;	Coumarin-carboxylic acid (Coumarin-CA) is a commercial fluorescent probe for · OH detection. The present invention selects Coumarin-CA to compare with compound 4. The reaction between OH and Coumarin-CA generates the fluorescent product 7-hydroxycoumarin-3-carboxylic acid, which has an emission light with a peak at 454 nm under excitation at 400 nm. Therefore, the reaction can be monitored by checking the fluorescence intensity I454. At the same time, the reaction of OH with compound 4 can reduce its absorption value at 610 nm, thus providing a simple method for monitoring the reaction. During the test, Coumarin-CA (100 muM) or Compound 4 (40 muM) was incubated with Fenton reagent EDTA-Fe2 + (100 muM) / H2O2 (10 mM) in sodium borate buffer (pH 9.0). In a competitive experiment, Coumarin-CA and compound 4 were pre-mixed, and then subjected to the · OH reaction. The reaction was performed in a 96-well plate, and the emission intensity I454 under 400 nm excitation was recorded every 10 seconds, and the UV-vis absorbance I610 at 610 nm was also recorded.

Reference： [1]Chemistry - A European Journal,2011,vol. 17,p. 10151 - 10160
[2]Journal of the American Chemical Society,2012,vol. 134,p. 1950 - 1953
[3]Patent: WO2013/106219,2013,A1 .Location in patent: Paragraph 0008; 0050-0066
[4]Organic and Biomolecular Chemistry,2014,vol. 12,p. 5936 - 5944
[5]Dalton Transactions,2015,vol. 44,p. 16061 - 16072
[6]Chemistry - A European Journal,2016,vol. 22,p. 7268 - 7280
[7]Dalton Transactions,2016,vol. 45,p. 12627 - 12631
[8]Chemical Communications,2018,vol. 54,p. 11945 - 11948
[9]Patent: CN111072699,2020,A .Location in patent: Paragraph 0090-0093

25
[ 531-81-7 ]
[ 107-19-7 ]
[ 71387-23-0 ]

Yield	Reaction Conditions	Operation in experiment
96%	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 6h;	Typical experimental procedure for the synthesis of prop-2-yn-1-yl 2-oxo-2H-chromene-3-carboxylate 1 A solution of coumarin-3-carboxylic acid (1.9 g, 0.01 mol), propargyl alcohol (0.56 ml, 0.01 mol), N,N-dicyclohexyl cabodiimide (2.3 g, 011 mol), and 4-dimethylaminopyridine (0.122 g, 0.001 mol) in dichloromethane was stirred at room temperature for 6 h. After 6 h, the precipitated N,N-dicyclohexylurea was filtered off and the filtrate was washedwith water, 5% acetic acid, and again with water. It was then dried over magnesium sulphate and the solvent was evaporated. The residue obtained was washed with petroleum ether to afford the ester 1 (2.4 g, 96%).
78%	With potassium hexafluorophosphate at 130℃; for 12h; Sealed tube; Green chemistry;
2.4 g	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 6h;

Reference： [1]Location in patent: experimental part Pramitha; Bahulayan [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 7, p. 2598 - 2603]
[2]Sonam, None; Shinde, Vikki N.; Kumar, Anil [Journal of Organic Chemistry, 2022, vol. 87, # 5, p. 2651 - 2661]
[3]Thasnim; Bahulayan [New Journal of Chemistry, 2017, vol. 41, # 22, p. 13483 - 13489]

26
[ 531-81-7 ]
[ 646-25-3 ]
[ 1416056-39-7 ]

Yield	Reaction Conditions	Operation in experiment
60%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 12h;	General procedure: Compounds 9e-35e were obtained by using one-pot reaction. A mixture of aromatic acid (6.30 mmol), EDCI (7.50 mmol), DMAP (0.60 mmol), and anhydrous dichloromethane (20 mL) was stirred to dissolve, then decane-diamine (3 mmol) was added and stirred at room temperature for 12 h. The mixture solution was filtered under reduced pressure. After that, the residue was washed with little amount of CH2Cl2and water successively, and dried to give the solid. Then, the residue was purified on preparative TLC eluted with chloroform/methanol = 40:1-7:1 to yield compounds 26e, 28e, 30e, and 31e.

Reference： [1]Molecules,2019,vol. 24
[2]Molecules,2012,vol. 17,p. 10846 - 10863

27
[ 6066-82-6 ]
[ 531-81-7 ]
[ 148627-84-3 ]

Yield	Reaction Conditions	Operation in experiment
55%	With dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;	5.5 Coumarin-3-carboxylic acid succinimidyl ester (5) Coumarin-3-carboxylic acid (5 g, 25.2 mmol, 1eq) and N-hydroxysuccinimide (4.45 g, 37.8 mmol, 1.5 eq) were dissolved in anhydrous CH2Cl2 (50 mL). The mixture was cooled to 0 °C, and N,N'-dicyclohexylcarbodiimide (DCC, 7.80 g, 37.8 mmol, 1.5 eq) dissolved in 25 mL CH2Cl2 was added dropwise slowly. The mixture was stirred overnight at room temperature. The N,N'-dicyclohexylurea was filtered out, the residue was washed with CH2Cl2, and the filtrate was evaporated to dryness purified by column chromatography to afford 5 as faint yellow solid with yield 55%. 1H NMR (400 MHz, CDCl3): δ 8.81 (s, 1H, CH), 7.80-7.71 (t, 1H, Ar-H), 7.68 (d, J = 7.3 Hz, 1H, Ar-H), 7.40 (t, J = 7.6 Hz, 2H, Ar-H), 2.92 (s, 4H, CH2).
52%	With dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 30℃; for 8h;	2.2. Synthesis The intermediate compounds of ethyl 2-(quinolin-8-yloxy)acetateand 2-(quinolin-8-yloxy) acetohydrazide (QA)were synthesizedaccording to the previously reported reference [43]. A mixture ofcoumarin-3-carboxylic acid (0.57 g, 3.0mmol), N-hydroxysuccinimide(NHS) (0.37 g, 3.2mmol) anddicyclohexylcarbodiimide (DCC) (0.68 g, 3.3mmol) in of DMF (8mL)were stirred for about 8 h at room temperature. After filtration, thefiltrate was added to the mixture solvent (50 mL) of isopropanolhexanemixture (1/20) to obtain the intermediate 2,5-dioxopyrrolidin-1-yl-2-oxo-2H-chromene-3- carboxylate (DC) [44].Next, the mixture of the intermediate DC, QA (0.70 g, 3.2mmol) and4-Dimethylaminopyridine (0.39 g, 3.2mmol) in of DMF (10mL)werereacted at 85° C for 24 h. Then, pour the mixture into deionizedwater, extracting with dichloromethane. Collecting the organicphase, washed with saturated sodium chloride solution, and thendried by anhydrous sodium sulfate. The solvent was removed underreduced pressure to get crude product. The crude product was purifiedby column chromatography on silica gel with the eluent ofmethanol/dichloromethane (1/30, v/v) to obtained a pale yellowsolid 2-oxo-N’-(2-(quinolin-8-yloxy)acetyl)-2H-chromene-3-carbohydrazide(CHBQ) 0.61 g, yield (52%). 1H NMR (600MHz, CH3CN-d)δ(ppm): 11.72 (b, 1H), 10.82 (s, 1H), 9.00 (m, 1H,) 8.97 (s, 1H), 8.37 (d,J 8.4Hz, 1H), 7.97 (d, J 7.8Hz, 1H), 7.79 (m, 1H), 7.67 (d, J 8.4Hz1H), 7.60 (m, 2H), 7.52 (d, J 8.4Hz, 1H), 7.48 (t, J 7.2Hz, 1H), 7.41 (d,J 7.8Hz, 1H), 4.99 (s, 4H); 13C NMR (100MHz, DMSO-d6)δ (ppm)165.87, 160.37, 159.04, 154.51, 154.45, 149.92, 148.56, 140.43, 136.59,134.93, 130.87, 129.63, 127.27, 125.72, 122.51, 121.81, 118.80, 118.45,116.74, 113.09, 68.70. HRMS-ESI calcd for C21H15N3O5 (m/z) [M+H]:390.1084, found: 390.1085.
	With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 2.5h;	General procedure for synthesis of NHS ester General procedure: To a solution of carboxylic acid (1.0 equiv) in THF (10 mL) at 0 °C were added N-hydroxysuccinimide (1.0 equiv) and DCC (1.0 equiv). The resulting mixture was stirred for 30 min at 0 °C and 2 h at room temperature. The reaction mixture was filtered to remove the precipitates, and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (hexane/EtOAc) afforded the desired N-hydroxysuccinimidyl esters.

Reference： [1]Zhou, Li-Sheng; Yang, Ke-Wu; Feng, Lei; Xiao, Jian-Min; Liu, Cheng-Cheng; Zhang, Yi-Lin; Crowder, Michael W. [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 4, p. 949 - 954]
[2]Wang, Xiaoju; Wang, Haoping; Niu, Yan; Wang, Yunxia; Feng, Liheng [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2020, vol. 226]
[3]Kumar, Rishi; Nasi, Ravindranath; Bhasin, Milan; Khieu, Nam Huan; Hsieh, Margaret; Gilbert, Michel; Jarrell, Harold; Zou, Wei; Jennings, Harold J. [Carbohydrate Research, 2013, vol. 378, p. 45 - 55]

28
[ 13781-67-4 ]
[ 531-81-7 ]
[ 1422255-36-4 ]

Yield	Reaction Conditions	Operation in experiment
52%	Stage #1: 3-(2-hydroxyethyl)thiophene; 2-oxo-2H-chromene-3-carboxylic acid With dmap In dichloromethane; N,N-dimethyl-formamide at 0℃; for 0.5h; Inert atmosphere; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 24h; Inert atmosphere;	2.4.1 Synthesis of monomer 1 The thienyl derivative with coumarin was illustrated in Scheme 1. The coumarin containing carboxylic acid functionality (1 mmol) was reacted with 2-(3-thienyl)ethanol (1 mmol) in the presence of N,N-dimethylaminopyridine (DMAP) (2 mmol) in CH2Cl2/DMF (10 ml/2 ml), cooled to 0 °C and stirred under N2 for 30 min prior to addition of DCC to increase its reactivity. Dicyclohexylcarbodiimide (DCC) (2 mmol) was dissolved in 1-2 ml of CH2Cl2 and added to the stirring mixture at 0 °C [37]. The solution was stirred at room temperature under N2 for 24 h. The solvent was evaporated in vacuo. Dicyclohexyl urea (DCU) was removed by dissolving the crude product in CH2Cl2 and placed in the freezer for 30 min, then filtered through a crucible. The crude product was purified with column chromatography (EtOAc/hexane = 1.5/1) to afford pure thienyl-coumarin (ThC) compound as an off-white solid. The monomer was obtained in a 52% yield:

Reference： [1]Abd-El-Aziz; Dalgakiran; Kucukkaya; Wagner [Electrochimica Acta, 2013, vol. 89, p. 445 - 453]

29
[ 531-81-7 ]
[ 5326-38-5 ]
[ 312706-15-3 ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 2957 - 2964

30
[ 5832-44-0 ]
[ 531-81-7 ]
[ 1542158-13-3 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 796 - 799

31
[ 15513-52-7 ]
[ 531-81-7 ]
[ 1542158-14-4 ]
[ 1542158-15-5 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 796 - 799

32
[ 531-81-7 ]
[ 35108-00-0 ]
2-oxo-2H-chromene-3-carboxylic acid 4-decyloxyphenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	A Typical Procedure for the Synthesis of 2-Oxo-2H-chromene-3-carboxylic acid-4-octyloxy-phenylester (6a) General procedure: A mixture of coumarin-3-carboxylic acid 5a (1 g, 5.25 mmol), 1(3-dimethylaminopropyl-3-ethylcarbodiimide. hydrochloride) (EDCI) (1.1 g, 5.78 mmol), and mole equivalent ofDMAP (dimethyl amino pyridine, 0.70 g, 5.78 mmol) were taken in dichloromethane. Tothis reaction mixture, the 4-alkoxy phenol 4a (1.28 g, 5.78 mmol) was added, stirred atroom temperature for 5 h, and the progress of the reaction was monitored by TLC (ethylacetate: pet ether 1:1). After the completion of the reaction, the reaction mass was dilutedwith water and extracted with DCM (25 mL × 2). The organic layer was washed withsaturated brine solution and dried over anhydrous sodium sulfate. The crude product (6a)thus obtained was purified by column chromatography by using ethyl acetate: petroleumether (2:8) as eluent followed by recrystallization by ethanol. The 600 mg of yield wasobtained as white solid.The synthesis of intermediate 1-(benzyloxy)-4-alkoxybenzenes 3a-g and 4-(alkoxy)phenols 4a-g were reported in literature [36-38] and used here as key intermediates for thesynthesis of the new 4-alkoxyphenyl-coumarin-3-carboxylates 6a-e, 7a-g, 8a-e, and 9a-ecompounds to study their liquid crystal properties.

Reference： [1]Mahadevan, Kittappa M.; Harishkumar, Hosanagara N.; Masagalli, Jagadeesh N.; Srinivasa, Hosapalya T. [Molecular Crystals and Liquid Crystals, 2013, vol. 570, # 1, p. 20 - 35]

33
[ 531-81-7 ]
[ 13037-87-1 ]
2-oxo-2H-chromene-3-carboxylic acid 4-dodecyloxyphenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	A Typical Procedure for the Synthesis of 2-Oxo-2H-chromene-3-carboxylic acid-4-octyloxy-phenylester (6a) General procedure: A mixture of coumarin-3-carboxylic acid 5a (1 g, 5.25 mmol), 1(3-dimethylaminopropyl-3-ethylcarbodiimide. hydrochloride) (EDCI) (1.1 g, 5.78 mmol), and mole equivalent ofDMAP (dimethyl amino pyridine, 0.70 g, 5.78 mmol) were taken in dichloromethane. Tothis reaction mixture, the 4-alkoxy phenol 4a (1.28 g, 5.78 mmol) was added, stirred atroom temperature for 5 h, and the progress of the reaction was monitored by TLC (ethylacetate: pet ether 1:1). After the completion of the reaction, the reaction mass was dilutedwith water and extracted with DCM (25 mL × 2). The organic layer was washed withsaturated brine solution and dried over anhydrous sodium sulfate. The crude product (6a)thus obtained was purified by column chromatography by using ethyl acetate: petroleumether (2:8) as eluent followed by recrystallization by ethanol. The 600 mg of yield wasobtained as white solid.The synthesis of intermediate 1-(benzyloxy)-4-alkoxybenzenes 3a-g and 4-(alkoxy)phenols 4a-g were reported in literature [36-38] and used here as key intermediates for thesynthesis of the new 4-alkoxyphenyl-coumarin-3-carboxylates 6a-e, 7a-g, 8a-e, and 9a-ecompounds to study their liquid crystal properties.

Reference： [1]Mahadevan, Kittappa M.; Harishkumar, Hosanagara N.; Masagalli, Jagadeesh N.; Srinivasa, Hosapalya T. [Molecular Crystals and Liquid Crystals, 2013, vol. 570, # 1, p. 20 - 35]

34
[ 531-81-7 ]
[ 13224-40-3 ]
2-oxo-2H-chromene-3-carboxylic acid 4-tetradecyloxyphenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	A Typical Procedure for the Synthesis of 2-Oxo-2H-chromene-3-carboxylic acid-4-octyloxy-phenylester (6a) General procedure: A mixture of coumarin-3-carboxylic acid 5a (1 g, 5.25 mmol), 1(3-dimethylaminopropyl-3-ethylcarbodiimide. hydrochloride) (EDCI) (1.1 g, 5.78 mmol), and mole equivalent ofDMAP (dimethyl amino pyridine, 0.70 g, 5.78 mmol) were taken in dichloromethane. Tothis reaction mixture, the 4-alkoxy phenol 4a (1.28 g, 5.78 mmol) was added, stirred atroom temperature for 5 h, and the progress of the reaction was monitored by TLC (ethylacetate: pet ether 1:1). After the completion of the reaction, the reaction mass was dilutedwith water and extracted with DCM (25 mL × 2). The organic layer was washed withsaturated brine solution and dried over anhydrous sodium sulfate. The crude product (6a)thus obtained was purified by column chromatography by using ethyl acetate: petroleumether (2:8) as eluent followed by recrystallization by ethanol. The 600 mg of yield wasobtained as white solid.The synthesis of intermediate 1-(benzyloxy)-4-alkoxybenzenes 3a-g and 4-(alkoxy)phenols 4a-g were reported in literature [36-38] and used here as key intermediates for thesynthesis of the new 4-alkoxyphenyl-coumarin-3-carboxylates 6a-e, 7a-g, 8a-e, and 9a-ecompounds to study their liquid crystal properties.

Reference： [1]Mahadevan, Kittappa M.; Harishkumar, Hosanagara N.; Masagalli, Jagadeesh N.; Srinivasa, Hosapalya T. [Molecular Crystals and Liquid Crystals, 2013, vol. 570, # 1, p. 20 - 35]

35
[ 531-81-7 ]
[ 67399-92-2 ]
2-oxo-2H-chromene-3-carboxylic acid 4-octadecyloxyphenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	A Typical Procedure for the Synthesis of 2-Oxo-2H-chromene-3-carboxylic acid-4-octyloxy-phenylester (6a) General procedure: A mixture of coumarin-3-carboxylic acid 5a (1 g, 5.25 mmol), 1(3-dimethylaminopropyl-3-ethylcarbodiimide. hydrochloride) (EDCI) (1.1 g, 5.78 mmol), and mole equivalent ofDMAP (dimethyl amino pyridine, 0.70 g, 5.78 mmol) were taken in dichloromethane. Tothis reaction mixture, the 4-alkoxy phenol 4a (1.28 g, 5.78 mmol) was added, stirred atroom temperature for 5 h, and the progress of the reaction was monitored by TLC (ethylacetate: pet ether 1:1). After the completion of the reaction, the reaction mass was dilutedwith water and extracted with DCM (25 mL × 2). The organic layer was washed withsaturated brine solution and dried over anhydrous sodium sulfate. The crude product (6a)thus obtained was purified by column chromatography by using ethyl acetate: petroleumether (2:8) as eluent followed by recrystallization by ethanol. The 600 mg of yield wasobtained as white solid.The synthesis of intermediate 1-(benzyloxy)-4-alkoxybenzenes 3a-g and 4-(alkoxy)phenols 4a-g were reported in literature [36-38] and used here as key intermediates for thesynthesis of the new 4-alkoxyphenyl-coumarin-3-carboxylates 6a-e, 7a-g, 8a-e, and 9a-ecompounds to study their liquid crystal properties.

Reference： [1]Mahadevan, Kittappa M.; Harishkumar, Hosanagara N.; Masagalli, Jagadeesh N.; Srinivasa, Hosapalya T. [Molecular Crystals and Liquid Crystals, 2013, vol. 570, # 1, p. 20 - 35]

36
[ 531-81-7 ]
[ 3780-50-5 ]
2-oxo-2H-chromene-3-carboxylic acid 4-octyloxyphenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	A Typical Procedure for the Synthesis of 2-Oxo-2H-chromene-3-carboxylic acid-4-octyloxy-phenylester (6a) A mixture of coumarin-3-carboxylic acid 5a (1 g, 5.25 mmol), 1(3-dimethylaminopropyl-3-ethylcarbodiimide. hydrochloride) (EDCI) (1.1 g, 5.78 mmol), and mole equivalent ofDMAP (dimethyl amino pyridine, 0.70 g, 5.78 mmol) were taken in dichloromethane. Tothis reaction mixture, the 4-alkoxy phenol 4a (1.28 g, 5.78 mmol) was added, stirred atroom temperature for 5 h, and the progress of the reaction was monitored by TLC (ethylacetate: pet ether 1:1). After the completion of the reaction, the reaction mass was dilutedwith water and extracted with DCM (25 mL × 2). The organic layer was washed withsaturated brine solution and dried over anhydrous sodium sulfate. The crude product (6a)thus obtained was purified by column chromatography by using ethyl acetate: petroleumether (2:8) as eluent followed by recrystallization by ethanol. The 600 mg of yield wasobtained as white solid.The synthesis of intermediate 1-(benzyloxy)-4-alkoxybenzenes 3a-g and 4-(alkoxy)phenols 4a-g were reported in literature [36-38] and used here as key intermediates for thesynthesis of the new 4-alkoxyphenyl-coumarin-3-carboxylates 6a-e, 7a-g, 8a-e, and 9a-ecompounds to study their liquid crystal properties.Spectroscopic Details 2-Oxo-2H-chromene-3-carboxylic acid-4-octyloxyphenylester(6a)Yield: 94%; mp: 114C-118C; 1H NMR (400 MHz, DMSO-d6): δ = 9.06 (s, 1H),8.0 (dd, J = 1.20 Hz, 1.6 Hz, 1H), 7.78-7.825 (m, 1H), 7.44-7.50 (m, 2H), 7.16-7.2022 K. M. Mahadevan et al.(m, 2H), 6.99-7.02 (m, 2H), 3.99 (t, J = 6.4 Hz, 2H), 1.69-1.75 (m, 2H), 1.40-1.45(m, 2H), 1.29-1.33 (m, 8H), 0.86-0.88 (m, 3H) ppm; 13C NMR (100 MHz, DMSO-d6):161.84, 157.02, 156.36, 155.25, 150.65, 144.00, 135.46, 131.04, 125.46, 123.04, 118.32,117.13, 116.73, 115.53, 68.31, 31.71, 29.21, 29.14, 26.00, 22.55, 14.43 ppm; IR(KBr): v =1726(aromatic C=O) cm-1, 1759(ester C=O) cm-1; GCMS = 394.1; elemental analysiscalcd for C24H26O5 = C, 73.08, H, 6.64% Found: C, 73.66, H, 6.66%.

Reference： [1]Mahadevan, Kittappa M.; Harishkumar, Hosanagara N.; Masagalli, Jagadeesh N.; Srinivasa, Hosapalya T. [Molecular Crystals and Liquid Crystals, 2013, vol. 570, # 1, p. 20 - 35]

37
[ 941-91-3 ]
[ 531-81-7 ]
1-methyl-3-(2-oxo-2H-chromen-3-yl)quinolin-2(1H)-one [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2016,vol. 81,p. 424 - 432

38
[ 531-81-7 ]
[ 7188-38-7 ]
[ 137-07-5 ]
N-(tert-butyl)-2-(2,3,4,5-tetrahydro-2,4-dioxobenzo[b][1,4]thiazepin-3-yl)-2-(2-hydroxyphenyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With immobilized Aspergillus niger lipase bonded on Fe₃O₄ nanoparticles In ethanol at 20℃; for 1h; Green chemistry;	3.1 General Procedure for the Preparation of Benzothiazepines General procedure: A mixture of coumarin-3-carboxylic acid derivative (1 mmol),alkyl isocyanide (1 mmol), aminobenzothiol (0.104 ml,1 mmol), and NBC (0.025 g) in 5 ml ethanol was stirred atroom temperature for 1 h. When the reaction (TLC, eluent:AcOEt/n-hexane 1:1) was completed, the nano biocatalyst was separated using a magnet, the solvent was removed under reduced pressure and the residue was separated by chromatography plates using n-hexane/AcOEt as eluent.

Reference： [1]Baharfar, Robabeh; Mohajer, Saadieh [Catalysis Letters, 2016, vol. 146, # 9, p. 1729 - 1742]

39
[ 531-81-7 ]
[ 7188-38-7 ]
[ 137-07-5 ]
C₂₁H₂₀N₂O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With immobilized Aspergillus niger lipase bonded on Fe₃O₄ nanoparticles In 1,4-dioxane at 20℃; for 1h; Green chemistry;	3.3 General Procedure for the Synthesisof Spirobenzothiazine Chromans General procedure: A mixture of coumarin-3-carboxylic acid derivative(1 mmol), alkyl isocyanide (1 mmol), aminobenzothiol(0.104 ml, 1 mmol), and NBC (0.025 g) in 5 ml dioxane was stirred at room temperature for 1 h. When the reaction (TLC,eluent: AcOEt/n-hexane 1:1) was completed, the NBC was separated using a magnet, the solvent was removed under reduced pressure and the residue was separated by chromatography plates using n-hexane/AcOEt as eluent.

Reference： [1]Baharfar, Robabeh; Mohajer, Saadieh [Catalysis Letters, 2016, vol. 146, # 9, p. 1729 - 1742]

40
[ 531-81-7 ]
[ 931-53-3 ]
[ 137-07-5 ]
N-cyclohexyl-2',3-dioxo-3,4-dihydrospiro[benzo[b][1,4]thiazine-2,3'-chromane]-4'-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With immobilized Aspergillus niger lipase bonded on Fe₃O₄ nanoparticles In 1,4-dioxane at 20℃; for 1h; Green chemistry;	3.3 General Procedure for the Synthesisof Spirobenzothiazine Chromans General procedure: A mixture of coumarin-3-carboxylic acid derivative(1 mmol), alkyl isocyanide (1 mmol), aminobenzothiol(0.104 ml, 1 mmol), and NBC (0.025 g) in 5 ml dioxane was stirred at room temperature for 1 h. When the reaction (TLC,eluent: AcOEt/n-hexane 1:1) was completed, the NBC was separated using a magnet, the solvent was removed under reduced pressure and the residue was separated by chromatography plates using n-hexane/AcOEt as eluent.

Reference： [1]Baharfar, Robabeh; Mohajer, Saadieh [Catalysis Letters, 2016, vol. 146, # 9, p. 1729 - 1742]

41
[ 531-81-7 ]
[ 431879-42-4 ]
3-O-(coumarin-3-ylcarbonyl)-28-O-tritylbetulin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h;	General procedure for the esterification of betulin derivatives General procedure: DMAP(3.0-4.8 mmol), the corresponding acid (2.5-3.0 mmol) and EDC-HCl(3.0-4.8 mmol) were added to a solution of 28-tritylbetulin (or betulin) (1 mmol) in dry CH2Cl2 (20 ml). The mixture was stirred at room temperature. Reaction completion was monitored by TLC. The mixture was quenched by addition of water (20 ml). The organic layer was washed with saturated sodium bicarbonate (20 ml) and brine (20 ml), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purifiedby silica gel column chromatography with ethyl acetate-light petroleum as an eluent to give compounds 3, 5, 6. 3-O-(Coumarin-3-ylcarbonyl)-28-O-tritylbetulin 3a. White solid, yield 90%, mp 159-160 °C. IR (KBr, ν/cm-1): 3059, 2940, 1759, 1707, 1449,1242. 1H NMR (CDCl3) δ: 8.45 (s, 1H, coumarinyl H-4), 7.20-7.70 (m,19H), 4.71 (dd, 1H, H-3, J 10.2, 5.7 Hz), 4.58, 4.52 (2 s, 2×1H, H-29),3.13, 2.91 (2d, 2×1H, H-28, J 8.4 Hz), 2.16-2.22 (m, 3H, H-2 and H-19),1.64 (s, 3H, Me), 0.98 (s, 3H, Me), 0.94 (s, 3H, Me), 0.91 (s, 3H, Me),0.83 (s, 3H, Me), 0.52 (s, 3H, Me). MS (MALDI-TOF), m/z: 878.80[M+Na]+, 894.76 [M+K]+.

Reference： [1]Wang, Ge-Yang; Jin, Lei; Piao, Feng-Yu; Han, Rong-Bi [Mendeleev Communications, 2017, vol. 27, # 1, p. 93 - 94]

42
[ 531-81-7 ]
[ 87156-40-9 ]
C₁₂H₁₀N₄O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 3h;
65%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃; for 3h;	14 Coumarin 3-carboxylate (380.3 mg, 2 mmol),2-Azidoethylamine (206 mg, 2.4 mmol),Et3N (6 mmol, 0.83 ml.),EDC (1.15 g, 6 mmol) andHOBt (810.7 mg, 6 mmol) was dissolved in DMF (30 ml). After reaction for 3 h at room temperature, water (10 ml)The product was extracted with DCM (3 × 30 ml)The combined organic phases were washed successively with saturated NaHCO 3 (20 ml), NH 4 Cl (20 ml) and NaCl (20 ml) and dried over anhydrous Na 2 SO 4.Under reduced pressure, the solvent was removed by rotary evaporation, and 10 ml of CH2Cl2 and 2 g of 60-100 mesh silica gel were added. Using ethyl acetate / petroleum ether = 1/4 as eluent,Flash column chromatography gave compound 21 (white solid, 65% yield).
65%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 3h;

Reference： [1]Li, Zhihong; Huang, Rong; Xu, Hongtao; Chen, Jiakang; Zhan, Yuexiong; Zhou, Xianhao; Chen, Hongli; Jiang, Biao [Organic Letters, 2017, vol. 19, # 18, p. 4972 - 4975]
[2]Current Patent Assignee: SHANGHAITECH UNIVERSITY - CN107400072, 2017, A Location in patent: Paragraph 0037; 0122; 0123
[3]Huang, Rong; Li, Zhihong; Ren, Peiling; Chen, Wenzhang; Kuang, Yuanyuan; Chen, Jiakang; Zhan, Yuexiong; Chen, Hongli; Jiang, Biao [European Journal of Organic Chemistry, 2018, vol. 2018, # 6, p. 829 - 836]

43
[ 531-81-7 ]
[ 95-55-6 ]
[ 1846-95-3 ]

Yield	Reaction Conditions	Operation in experiment
66%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Stage #2: 2-amino-phenol With triethylamine In dichloromethane at 20℃; for 12h;	4.1.3. Synthesis of 2-Oxo-N-substituted phenyl-2H-chromene-3-carboxamide (13a-13r) General procedure: To the coumarin-3-carboxylic acid (1.0 g) in 20 ml dry DCM was added EDCl-HCl (0.6 g), and HOBt (0.55 g). After stirring at RT for 30 min, the amine (1.1 equiv) was added followed by triethylamine (1 ml). The reaction mixture was stirred at RT for 12 h. The progress of the reaction was monitored by using TLC (ethyl acetate/n-hexane: 30:70). After completion of the reaction, the reaction mixture was diluted with DCM and washed with 1M HCl solution. The organic layer was separated and further treated with saturated sodium bicarbonate solution followed by brine solution. The organic layer was dried on sodium sulfate and concentrated by using rota-evaporator. The crude product was recrystallized in Dichloromethane: Pentane (2:8).
54%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: 2-amino-phenol In dichloromethane at 20℃; for 4h; Inert atmosphere;

Reference： [1]Jadhav, Hemant R.; Jain, Priti; Wadhwa, Pankaj [Letters in drug design and discovery, 2020, vol. 17, # 4, p. 416 - 425]
[2]Fonseca, André; Matos, Maria João; Vilar, Santiago; Kachler, Sonja; Klotz, Karl-Norbert; Uriarte, Eugenio; Borges, Fernanda [Chemical Biology and Drug Design, 2018, vol. 91, # 1, p. 245 - 256]

44
[ 531-81-7 ]
[ 95-51-2 ]
[ 74556-29-9 ]

Yield	Reaction Conditions	Operation in experiment
68%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: o-chloroaniline In dichloromethane at 20℃; for 4h; Inert atmosphere;
66%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Stage #2: o-chloroaniline With triethylamine In dichloromethane at 20℃; for 12h;	4.1.3. Synthesis of 2-Oxo-N-substituted phenyl-2H-chromene-3-carboxamide (13a-13r) General procedure: To the coumarin-3-carboxylic acid (1.0 g) in 20 ml dry DCM was added EDCl-HCl (0.6 g), and HOBt (0.55 g). After stirring at RT for 30 min, the amine (1.1 equiv) was added followed by triethylamine (1 ml). The reaction mixture was stirred at RT for 12 h. The progress of the reaction was monitored by using TLC (ethyl acetate/n-hexane: 30:70). After completion of the reaction, the reaction mixture was diluted with DCM and washed with 1M HCl solution. The organic layer was separated and further treated with saturated sodium bicarbonate solution followed by brine solution. The organic layer was dried on sodium sulfate and concentrated by using rota-evaporator. The crude product was recrystallized in Dichloromethane: Pentane (2:8).
	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1.5h; Stage #2: o-chloroaniline at 0℃;	8 General procedure: To compound 2 (5.0mmol, 0.95g) dissolved in dry DMF (30mL) aniline (6.0mmol, 1mL) was added and the mixture was stirred at iced water. Once 2 was completely dissolved, DIEA (15.0mmol, 1.94g) and T3P (propyl phosphoric acid anhydride, 5.5mmol, 1.75g) were added gradually with stirring and cooling for 40min. After mixed with the appropriate water, the solution was extracted with ethyl acetate, and then washed with water for three times, and the product was purified by column chromatography to give a white solid.

Reference： [1]Fonseca, André; Matos, Maria João; Vilar, Santiago; Kachler, Sonja; Klotz, Karl-Norbert; Uriarte, Eugenio; Borges, Fernanda [Chemical Biology and Drug Design, 2018, vol. 91, # 1, p. 245 - 256]
[2]Jadhav, Hemant R.; Jain, Priti; Wadhwa, Pankaj [Letters in drug design and discovery, 2020, vol. 17, # 4, p. 416 - 425]
[3]Yu, Xiang; Teng, Peng; Zhang, Ya-Ling; Xu, Zhao-Jun; Zhang, Ming-Zhi; Zhang, Wei-Hua [Fitoterapia, 2018, vol. 127, p. 387 - 395]

45
[ 531-81-7 ]
[ 106-47-8 ]
[ 1847-02-5 ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Stage #2: 4-chloro-aniline With triethylamine In dichloromethane at 20℃; for 12h;	4.1.3. Synthesis of 2-Oxo-N-substituted phenyl-2H-chromene-3-carboxamide (13a-13r) General procedure: To the coumarin-3-carboxylic acid (1.0 g) in 20 ml dry DCM was added EDCl-HCl (0.6 g), and HOBt (0.55 g). After stirring at RT for 30 min, the amine (1.1 equiv) was added followed by triethylamine (1 ml). The reaction mixture was stirred at RT for 12 h. The progress of the reaction was monitored by using TLC (ethyl acetate/n-hexane: 30:70). After completion of the reaction, the reaction mixture was diluted with DCM and washed with 1M HCl solution. The organic layer was separated and further treated with saturated sodium bicarbonate solution followed by brine solution. The organic layer was dried on sodium sulfate and concentrated by using rota-evaporator. The crude product was recrystallized in Dichloromethane: Pentane (2:8).
41%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: 4-chloro-aniline In dichloromethane at 20℃; for 4h; Inert atmosphere;
	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1.5h; Stage #2: 4-chloro-aniline at 0℃;	10 General procedure: To compound 2 (5.0mmol, 0.95g) dissolved in dry DMF (30mL) aniline (6.0mmol, 1mL) was added and the mixture was stirred at iced water. Once 2 was completely dissolved, DIEA (15.0mmol, 1.94g) and T3P (propyl phosphoric acid anhydride, 5.5mmol, 1.75g) were added gradually with stirring and cooling for 40min. After mixed with the appropriate water, the solution was extracted with ethyl acetate, and then washed with water for three times, and the product was purified by column chromatography to give a white solid.

Reference： [1]Jadhav, Hemant R.; Jain, Priti; Wadhwa, Pankaj [Letters in drug design and discovery, 2020, vol. 17, # 4, p. 416 - 425]
[2]Fonseca, André; Matos, Maria João; Vilar, Santiago; Kachler, Sonja; Klotz, Karl-Norbert; Uriarte, Eugenio; Borges, Fernanda [Chemical Biology and Drug Design, 2018, vol. 91, # 1, p. 245 - 256]
[3]Yu, Xiang; Teng, Peng; Zhang, Ya-Ling; Xu, Zhao-Jun; Zhang, Ming-Zhi; Zhang, Wei-Hua [Fitoterapia, 2018, vol. 127, p. 387 - 395]

46
[ 531-81-7 ]
[ 106-40-1 ]
[ 74555-99-0 ]

Yield	Reaction Conditions	Operation in experiment
71%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Stage #2: 4-bromo-aniline With triethylamine In dichloromethane at 20℃; for 12h;	4.1.3. Synthesis of 2-Oxo-N-substituted phenyl-2H-chromene-3-carboxamide (13a-13r) General procedure: To the coumarin-3-carboxylic acid (1.0 g) in 20 ml dry DCM was added EDCl-HCl (0.6 g), and HOBt (0.55 g). After stirring at RT for 30 min, the amine (1.1 equiv) was added followed by triethylamine (1 ml). The reaction mixture was stirred at RT for 12 h. The progress of the reaction was monitored by using TLC (ethyl acetate/n-hexane: 30:70). After completion of the reaction, the reaction mixture was diluted with DCM and washed with 1M HCl solution. The organic layer was separated and further treated with saturated sodium bicarbonate solution followed by brine solution. The organic layer was dried on sodium sulfate and concentrated by using rota-evaporator. The crude product was recrystallized in Dichloromethane: Pentane (2:8).
34%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: 4-bromo-aniline In dichloromethane at 20℃; for 4h; Inert atmosphere;

Reference： [1]Jadhav, Hemant R.; Jain, Priti; Wadhwa, Pankaj [Letters in drug design and discovery, 2020, vol. 17, # 4, p. 416 - 425]
[2]Fonseca, André; Matos, Maria João; Vilar, Santiago; Kachler, Sonja; Klotz, Karl-Norbert; Uriarte, Eugenio; Borges, Fernanda [Chemical Biology and Drug Design, 2018, vol. 91, # 1, p. 245 - 256]

47
[ 531-81-7 ]
[ 57260-71-6 ]
C₁₉H₂₂N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With benzotriazol-1-ol; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Stage #2: tert-butyl piperazine-1-carboxylate In dichloromethane at 20℃; for 16h;	4-(2-oxo-2H-chromene-3-carbonyl)piperazine-1-carboxylate(3) To a solution of coumarin-3-carboxyl acid derivatives 2(1.80 g, 9.5 mmol) in 30 mL dry dichloromethane (DCM)was added EDCI (2.18 g, 11.4 mmol), HOBT (1.28 mg,9.5 mmol) and N,N-diisopropylethylamine (2.45 g,19 mmol) at 0 °C. After 0.5 h, 1-Boc-piperazine (1.77 g,9.5 mmol) was added, and the reaction mixture was stirredat room temperature for 16 h. The mixtures were concentratedand the residue was extracted by ethyl acetate(EtOAc) and water. The organic layers was combined, driedover MgSO4, and evaporated under reduced pressure. Theresidue was further purified by flash column chromatographywith petroleum ether/EtOAc (1:1) to producedcompound 3 as a white solid (2.87 g, 85% yield). m.p.153-154 °C. 1H NMR (600 MHz, CDCl3) δ 7.95 (s, 1H),7.61 (ddd, J = 8.6, 7.4, 1.4 Hz, 1H), 7.55 (dd, J = 7.7,1.2 Hz, 1H), 7.37 (d, J = 8.3 Hz, 1H), 7.33 (dd, J = 7.6,7.4 Hz, 1H), 3.74 (s, 2H), 3.55 (t, J = 4.5 Hz, 2H), 3.50 (t, J= 4.5 Hz, 2H), 3.36 (s, 2H), 1.47 (s, 9H). 13C NMR(150 MHz, CDCl3) δ 163.8, 158.1, 154.6, 154.3, 143.8,133.2, 128.8, 125.1, 125.0, 118.0, 117.0, 80.5, 47.2, 42.3,28.5. ESI-MS m/z: 359.1 [M+H]+.
	With benzotriazol-1-ol; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;

Reference： [1]Zhang, Juan; Jiang, Cheng-Shi [Medicinal Chemistry Research, 2018, vol. 27, # 6, p. 1717 - 1727]
[2]Feng, Yu-Mei; Liu, Li-Wei; Qi, Pu-Ying; Xiao, Wan-Lin; Yang, Song; Zhang, Tai-Hong; Zhou, Xiang [Journal of Agricultural and Food Chemistry, 2022]

48
[ 531-81-7 ]
[ 108-91-8 ]
[ 4021-23-2 ]

Yield	Reaction Conditions	Operation in experiment
88%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: cyclohexylamine With dmap In dichloromethane at 20℃;	4.1.21 General procedure for the synthesis of coumarin derivatives 8a-g General procedure: 3-Carboxycoumarin 6 (1mmol) was dissolved in 10mL of dichloromethane and DCC (1mmol) was added to the mixture. The resulting reaction mixture was stirred for 1h at room temperature. Then appropriate amine 7a-g (1mmol) and DMAP (10mol%) were added sand stirring continued at room temperature for 3-4h. The progress of the reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was diluted with DCM (5mL) and solid formed was separated by filtration. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel (60-120 mesh) column chromatography using 1% MeOH in CHCl3 as eluent.
88%	With potassium hexafluorophosphate at 130℃; for 12h; Sealed tube; Green chemistry;
	With propyl phosphoric acid anhydride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0℃; for 0.666667h;	21 General procedure: To compound 2 (5.0mmol, 0.95g) dissolved in dry DMF (30mL) aniline (6.0mmol, 1mL) was added and the mixture was stirred at iced water. Once 2 was completely dissolved, DIEA (15.0mmol, 1.94g) and T3P (propyl phosphoric acid anhydride, 5.5mmol, 1.75g) were added gradually with stirring and cooling for 40min. After mixed with the appropriate water, the solution was extracted with ethyl acetate, and then washed with water for three times, and the product was purified by column chromatography to give a white solid.

Reference： [1]Butcher, R. J.; Katiyar, Diksha; Sharma, Rajesh Kumar; Singh, Vineeta; Tiwari, Neha [Bioorganic Chemistry, 2020, vol. 98]
[2]Sonam, None; Shinde, Vikki N.; Kumar, Anil [Journal of Organic Chemistry, 2022, vol. 87, # 5, p. 2651 - 2661]
[3]Yu, Xiang; Teng, Peng; Zhang, Ya-Ling; Xu, Zhao-Jun; Zhang, Ming-Zhi; Zhang, Wei-Hua [Fitoterapia, 2018, vol. 127, p. 387 - 395]

49
[ 531-81-7 ]
[ 2924-15-4 ]
2-oxo-2H-chromene-3-carboxylic acid N'-(2-fluoro-phenyl)-hydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0℃; for 4h;	General procedure: To compound 2 (5.0mmol, 0.95g) dissolved in anhydrous CH2Cl2 (30mL) (2-chlorophenyl) hydrazine hydrochloride (6.0mmol, 1.08g) was added and the mixture was stirred at iced water. Once 2 was completely dissolved, DMAP (4-dimethylaminopyridine, 77.2mmol, 1.53g) and EDCI (carbodiimide hydrochloride, 6.0mmol, 1.15g) were added gradually with stirring and cooling for 4h. The reaction mixture was extracted with saturated brine for three times. After took off the solvent, the resulting precipitate was purified by column chromatography to give an orange solid.

Reference： [1]Fitoterapia,2018,vol. 127,p. 387 - 395

50
[ 531-81-7 ]
[ 2924-16-5 ]
2-oxo-2H-chromene-3-carboxylic acid N'-(3-fluoro-phenyl)-hydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0℃; for 4h;	General procedure: To compound 2 (5.0mmol, 0.95g) dissolved in anhydrous CH2Cl2 (30mL) (2-chlorophenyl) hydrazine hydrochloride (6.0mmol, 1.08g) was added and the mixture was stirred at iced water. Once 2 was completely dissolved, DMAP (4-dimethylaminopyridine, 77.2mmol, 1.53g) and EDCI (carbodiimide hydrochloride, 6.0mmol, 1.15g) were added gradually with stirring and cooling for 4h. The reaction mixture was extracted with saturated brine for three times. After took off the solvent, the resulting precipitate was purified by column chromatography to give an orange solid.

Reference： [1]Fitoterapia,2018,vol. 127,p. 387 - 395

51
[ 138907-68-3 ]
[ 531-81-7 ]
ethyl 1-(4-fluorophenyl)-5-(2-oxo-2H-chromene-3-carboxamido)-1H-pyrazole-4 carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With pyridine; trichlorophosphate;	General procedure: Intermediate 4 (0.001mol) and 5 (0.001mol) were dissolved in pyridine, phosphorus oxychloride is slowly added dropwise under ice bath conditions, then at 40-60C reacted for 5-8h. Finally, the mixture was poured into 30mL saturated Na2CO3 solution and stirred well. After the mixture was acidified, the saturated CuSO4 solution was used to remove pyridine, which greatly improved the purity and yield of the product. The data for compounds 8I-8VI are provided in the supporting information.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 157,p. 81 - 87

52
[ 531-81-7 ]
[ 15001-11-3 ]
ethyl 5-(2-oxo-2H-chromene-3-carboxamido)-1-(p-tolyl)-1H-pyrazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With pyridine; trichlorophosphate;	General procedure: Intermediate 4 (0.001mol) and 5 (0.001mol) were dissolved in pyridine, phosphorus oxychloride is slowly added dropwise under ice bath conditions, then at 40-60C reacted for 5-8h. Finally, the mixture was poured into 30mL saturated Na2CO3 solution and stirred well. After the mixture was acidified, the saturated CuSO4 solution was used to remove pyridine, which greatly improved the purity and yield of the product. The data for compounds 8I-8VI are provided in the supporting information.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 157,p. 81 - 87

53
[ 531-81-7 ]
[ 51516-70-2 ]
N-(4-cyano-1-(4-fluorophenyl)-1H-pyrazol-5-yl)-2-oxo-2H-chromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With pyridine; trichlorophosphate;	General procedure: Intermediate 4 (0.001mol) and 5 (0.001mol) were dissolved in pyridine, phosphorus oxychloride is slowly added dropwise under ice bath conditions, then at 40-60C reacted for 5-8h. Finally, the mixture was poured into 30mL saturated Na2CO3 solution and stirred well. After the mixture was acidified, the saturated CuSO4 solution was used to remove pyridine, which greatly improved the purity and yield of the product. The data for compounds 8I-8VI are provided in the supporting information.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 157,p. 81 - 87

54
[ 531-81-7 ]
[ 51516-67-7 ]
N-(1-(4-chlorophenyl)-4-cyano-1H-pyrazol-5-yl)-2-oxo-2H-chromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With pyridine; trichlorophosphate;	General procedure: Intermediate 4 (0.001mol) and 5 (0.001mol) were dissolved in pyridine, phosphorus oxychloride is slowly added dropwise under ice bath conditions, then at 40-60C reacted for 5-8h. Finally, the mixture was poured into 30mL saturated Na2CO3 solution and stirred well. After the mixture was acidified, the saturated CuSO4 solution was used to remove pyridine, which greatly improved the purity and yield of the product. The data for compounds 8I-8VI are provided in the supporting information.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 157,p. 81 - 87

55
[ 531-81-7 ]
[ 103646-82-8 ]
N-(4-cyano-1-(p-tolyl)-1H-pyrazol-5-yl)-2-oxo-2H-chromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With pyridine; trichlorophosphate;	General procedure: Intermediate 4 (0.001mol) and 5 (0.001mol) were dissolved in pyridine, phosphorus oxychloride is slowly added dropwise under ice bath conditions, then at 40?60°C reacted for 5?8h. Finally, the mixture was poured into 30mL saturated Na2CO3 solution and stirred well. After the mixture was acidified, the saturated CuSO4 solution was used to remove pyridine, which greatly improved the purity and yield of the product. The data for compounds 8I-8VI are provided in the supporting information.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 157,p. 81 - 87

56
[ 3281-08-1 ]
[ 531-81-7 ]
2-oxo-2H-chromene-3-carboxylic acid N'-[2-(quinolin-8-yloxy)acetyl]hydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: 8-quinolinoxyacetic acid hydrazide; 2-oxo-2H-chromene-3-carboxylic acid In dichloromethane at 25 - 30℃; for 0.5h; Stage #2: With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In dichloromethane at 0 - 5℃;
78%	Stage #1: 8-quinolinoxyacetic acid hydrazide; 2-oxo-2H-chromene-3-carboxylic acid With 2,6-dimethylpyridine In dichloromethane at 25 - 30℃; for 0.5h; Stage #2: With O‐(1H‐benzotriazol‐1‐yl)‐N,N,N′,N′‐tetramethyluronium tetrafluoroborate In dichloromethane at 0 - 5℃; for 12h;	4.2.3. General procedure for the preparation of 2-oxo-N’-(2-phenoxy and heteroyloxy acetyl) -2H-chromene-3-carbohydrazide (6a-l) General procedure: To the mixture of compounds ( 4a-l, 0.0037 mol) in dry dichloromethane (20 mL), lutidine (1.2 vol.) was added at 25-30 °C followed by coumarin-3-carboxylic acid ( 5 , 0.0037 mol) and stirred at 25-30 °C for 30 min. The reaction mass was cooled to 0-5 °C and TBTU (0.0037 mol) was added by maintaining the temper- ature below 5 °C. The reaction mass was stirred overnight and monitored by TLC using chloroform: methanol (9: 1). The reaction mixture was diluted with 25 mL of dichloromethane followed by 1.5 N HCl solution (20 mL). The organic layer was washed with water (30 mL), dried over anhydrous sodium sulfate, concentrated to syrupy liquid and recrystallized by diethyl ether to obtain com- pounds ( 6a-l ).
52%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 8h; Stage #2: 8-quinolinoxyacetic acid hydrazide With dmap In acetonitrile at 85℃; for 24h;	1.3; 2.3; 3.3; 4.3 3), 0.19 g of coumarin-3-carboxylic acid (1.0 mmol), 0.14 g of N-hydroxysuccinimide (1.2 mmol) and 0.25 g of dicyclohexylcarbodiimide (1.2 mmol) were dissolved in 5 mL. DMF, reaction at room temperature for 8 h, the product was suction filtered, the filtrate was collected, and the filtrate was added to a mixed solution of isopropanol and n-hexane 1 /20. After solid precipitation, the solid was dissolved in 1 mL of acetonitrile, and 0.65 g of 2-(quinoline)-8-yloxy) acetohydrazide was added. (3.0 mmol) and 0.15 g of 4-dimethylaminopyridine (1.2 mmol) were refluxed at 85 ° C for 24 h, then the solvent was evaporated and extracted with dichloromethane and brine. The organic phase was collected, dried over anhydrous sodium sulfate and evaporated, evaporated, evaporated, evaporated, evaporated, evaporated,2-Oxo-N'_(2-(quinolin-8-yloxy)acetyl)-2-indole-benzopyran-3-formylhydrazide (0.52 mmol), yield 52%.

Reference： [1]Prashanth; Avin, B.R. Vijay; Thirusangu, Prabhu; Ranganatha, V. Lakshmi; Prabhakar; Sharath Chandra, J.N. Narendra; Khanum, Shaukath Ara [Biomedicine and Pharmacotherapy, 2019, vol. 112]
[2]Banumathi; Jyothi, Mahima; Khamees, Hussien Ahmed; Khanum, Shaukath Ara; Prabhakar, B. T.; Sherapura, Ankith; Zabiulla [Journal of Molecular Structure, 2022, vol. 1252]
[3]Current Patent Assignee: SHANXI UNIVERSITY - CN110156762, 2019, A Location in patent: Paragraph 0046-0047; 0050-0051; 0054-0055; 0058-0059; 0062

57
[ 5969-83-5 ]
[ 531-81-7 ]
C₂₀H₁₄ClNO₂ [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 5907 - 5911

58
[ 531-81-7 ]
[ 3475-21-6 ]
4-(2-(4-methylpyridin-2-yl)phenyl)chroman-2-one [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 5907 - 5911

59
[ 68236-21-5 ]
[ 531-81-7 ]
[ 931-53-3 ]
[ 62-53-3 ]
N-(1-(2-chloro-7-methylquinolin-3-yl)-2-(cyclohexylamino)-2-oxoethyl)-2-oxo-N-phenyl-2H-chromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	In methanol; at 20℃;	General procedure: 4.2.3. General procedure for the synthesis of chromene-3-carboxamide (L1-L14) The reaction between 2-chloroquinoline-3-carbaldehydes and amine in methanol, imine was first created, and then coumarin-3-carboxylic acid was added to the reaction and stirring was continued for 30 min. Imine intermediate was prepared for attacking by the nucleophilic isocyanides. The resulting solution was stirred at room temperature for 4-6 h. The reaction was completed after 4-6 h. The reaction mixture was cooled and filtered on Büchner funne (Yields: 69-90%). Scheme 3 shows a mechanism for the synthesis of chromene-3-carboxamide. 4.2.3.1. N-(1-(2-chloroquinolin-3-yl)-2-(cyclohexylamino)-2-oxoethyl)-2- oxo-N-phenyl-2H-chromene-3-carboxamide (L1). White Solid, Yield: 88%. m.p: 199-202 C. IR (KBr) (νmax, cm-1): 3280 (NH), 2930, 1728 (C]O), 1656 (C]O), 755; 1H NMR)500 MHz, CDCl3): δH:1.28-1.33 (m, 1H, CH), 1.39-1.64 (m, 4H, CH), 1.71-1.73 (m, 1H, CH), 1.82-1.84 (m, 1H, CH), 1.90-1.93 (m, 1H, CH), 2.08-2.10 (m, 1H, CH), 2.26-2.28(m, 1H, CH), 4.06-4.12 (m, 1H, CH), 6.93 (t, 1H, J=10 Hz, Ar-H), 6.98-7.06 (m, 2H, Ar-H), 7.09 (s, 1H, Ar-H), 7.20 (brs, 2H, NH+Ar-H), 7.26 (d, 1H, J=10 Hz, Ar-H), 7.34 (t, 1H, J=5 Hz, Ar-H), 7.51 (t, 1H, J=10 Hz, Ar-H), 7.56-7.59 (m, 2H, Ar- H), 7.70 (t, 2H, J=5 Hz, Ar-H), 7.91 (d, 1H, J=5 Hz, Ar-H), 8.05-8.09 (m, 2H, Ar-H), 8.10 (s, 1H, Ar-H). 13C NMR (125 MHz, CDCl3): δC: 25.4, 25.6, 25.8, 33.1, 33.6, 49.9, 62.6, 117.2, 118.3, 125.5, 126.1, 126.8, 127.1, 127.5, 128.34)2C), 128.39, 128.8, 129.1, 129.3, 131.3, 133.4, 138.3, 142.4, 143.4, 147.3, 151.3, 154.1, 159.1, 165.8, 167.0. Anal. Calcd. for C33H28ClN3O4: C, 70.02; H, 4.99; N, 7.42. Found: C, 70.42; H, 5.01; N, 7.63.

Reference： [1]Bioorganic Chemistry,2019,vol. 91

60
[ 68236-21-5 ]
[ 531-81-7 ]
[ 931-53-3 ]
[ 106-49-0 ]
N-(1-(2-chloro-7-methylquinolin-3-yl)-2-(cyclohexylamino)-2-oxoethyl)-2-oxo-N-p-tolyl-2H-chromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	In methanol; at 20℃;	General procedure: The reaction between 2-chloroquinoline-3-carbaldehydes and amine in methanol, imine was first created, and then coumarin-3-carboxylic acid was added to the reaction and stirring was continued for 30 min. Imine intermediate was prepared for attacking by the nucleophilic isocyanides. The resulting solution was stirred at room temperature for 4-6 h. The reaction was completed after 4-6 h. The reaction mixture was cooled and filtered on Büchner funne (Yields: 69-90%). Scheme 3 shows a mechanism for the synthesis of chromene-3-carboxamide.

Reference： [1]Bioorganic Chemistry,2019,vol. 91

61
[ 68236-21-5 ]
[ 531-81-7 ]
[ 931-53-3 ]
[ 108-44-1 ]
N-(1-(2-chloro-7-methylquinolin-3-yl)-2-(cyclohexylamino)-2-oxoethyl)-2-oxo-N-(m-tolyl)-2H-chromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	In methanol; at 20℃;	General procedure: The reaction between 2-chloroquinoline-3-carbaldehydes and amine in methanol, imine was first created, and then coumarin-3-carboxylic acid was added to the reaction and stirring was continued for 30 min. Imine intermediate was prepared for attacking by the nucleophilic isocyanides. The resulting solution was stirred at room temperature for 4-6 h. The reaction was completed after 4-6 h. The reaction mixture was cooled and filtered on Büchner funne (Yields: 69-90%). Scheme 3 shows a mechanism for the synthesis of chromene-3-carboxamide.

Reference： [1]Bioorganic Chemistry,2019,vol. 91

62
[ 531-81-7 ]
[ 159005-71-7 ]
N-((2S,3R)-3-hydroxy-4-((N-isobutyl-4-methoxyphenyl)sulfonamido)-1-phenylbutan-2-yl)-2-oxo-2H-chromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid; N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-4-methoxybenzenesulfonamide With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃; for 1.16667h; Inert atmosphere; Stage #2: With dmap In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere;	4.1.1 N-((2S,3R)-3-hydroxy-4-((N-isobutyl-4-methoxyphenyl)sulfonamido)-1-phenylbutan-2-yl)-2-oxo-2H-chromene-6-carboxamide (6a) General procedure: N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI, 0.029g, 0.15mmol) and 1-hydroxybenzotriazole (HOBt, 0.015g, 0.11mmol) were sequentially added in batches to a stirring solution of 2-oxo-2H-chromene-6-carboxylic acid (4a, 0.019g, 0.10mmol) and N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-4- methoxybenzenesulfonamide (9, 0.043g, 0.105mmol) in dry DMF (1mL) at 0°C under an argon atmosphere. The reaction mixture was stirred for 10minat 0°C and then additional 1h at room temperature. 4-Dimethylaminopyridine (DMAP, 0.0024g, 0.020mmol) was added and the reaction mixture was stirred for another 2h at room temperature. The solvent was removed under reduced pressure. Water (4mL) was added to the residue and extracted with ethyl acetate (3×4mL). The combined organic phases were dried over Na2SO4, and evaporated, in vacuo. The residue was purified by chromatography on a silica gel column (30×6cm). Elution with 1:1 to 2:3 hexanes-ethyl acetate gave 6a as pale yellow crystalline powder: yield 0.050g (87%);

Reference： [1]Zhu, Mei; Ma, Ling; Wen, Jiajia; Dong, Biao; Wang, Yujia; Wang, Zhen; Zhou, Jinming; Zhang, Guoning; Wang, Juxian; Guo, Ying; Liang, Chen; Cen, Shan; Wang, Yucheng [European Journal of Medicinal Chemistry, 2020, vol. 186]

63
[ 531-81-7 ]
[ 251105-80-3 ]
N-((2S,3R)-3-hydroxy-4-((N-isobutyl-4-nitrophenyl)sulfonamido)-1-phenylbutan-2-yl)-2-oxo-2H-chromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid; N-(3S-amino-2R-hydroxy-4-phenylbutyl)-N-isobutyl-4-nitro-benzenesulfonamide hydrochloride With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃; for 1.16667h; Inert atmosphere; Stage #2: With dmap In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere;	4.1.1 N-((2S,3R)-3-hydroxy-4-((N-isobutyl-4-methoxyphenyl)sulfonamido)-1-phenylbutan-2-yl)-2-oxo-2H-chromene-6-carboxamide (6a) General procedure: N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI, 0.029g, 0.15mmol) and 1-hydroxybenzotriazole (HOBt, 0.015g, 0.11mmol) were sequentially added in batches to a stirring solution of 2-oxo-2H-chromene-6-carboxylic acid (4a, 0.019g, 0.10mmol) and N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-4- methoxybenzenesulfonamide (9, 0.043g, 0.105mmol) in dry DMF (1mL) at 0°C under an argon atmosphere. The reaction mixture was stirred for 10minat 0°C and then additional 1h at room temperature. 4-Dimethylaminopyridine (DMAP, 0.0024g, 0.020mmol) was added and the reaction mixture was stirred for another 2h at room temperature. The solvent was removed under reduced pressure. Water (4mL) was added to the residue and extracted with ethyl acetate (3×4mL). The combined organic phases were dried over Na2SO4, and evaporated, in vacuo. The residue was purified by chromatography on a silica gel column (30×6cm). Elution with 1:1 to 2:3 hexanes-ethyl acetate gave 6a as pale yellow crystalline powder: yield 0.050g (87%);

Reference： [1]Zhu, Mei; Ma, Ling; Wen, Jiajia; Dong, Biao; Wang, Yujia; Wang, Zhen; Zhou, Jinming; Zhang, Guoning; Wang, Juxian; Guo, Ying; Liang, Chen; Cen, Shan; Wang, Yucheng [European Journal of Medicinal Chemistry, 2020, vol. 186]

64
[ 531-81-7 ]
[ 169280-56-2 ]
C₃₀H₃₃N₃O₆S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid; 4-amino-N-(2R,3S)(3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfonamide With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃; for 1.16667h; Inert atmosphere; Stage #2: With dmap In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere;	4.1.1 N-((2S,3R)-3-hydroxy-4-((N-isobutyl-4-methoxyphenyl)sulfonamido)-1-phenylbutan-2-yl)-2-oxo-2H-chromene-6-carboxamide (6a) General procedure: N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI, 0.029g, 0.15mmol) and 1-hydroxybenzotriazole (HOBt, 0.015g, 0.11mmol) were sequentially added in batches to a stirring solution of 2-oxo-2H-chromene-6-carboxylic acid (4a, 0.019g, 0.10mmol) and N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-4- methoxybenzenesulfonamide (9, 0.043g, 0.105mmol) in dry DMF (1mL) at 0°C under an argon atmosphere. The reaction mixture was stirred for 10minat 0°C and then additional 1h at room temperature. 4-Dimethylaminopyridine (DMAP, 0.0024g, 0.020mmol) was added and the reaction mixture was stirred for another 2h at room temperature. The solvent was removed under reduced pressure. Water (4mL) was added to the residue and extracted with ethyl acetate (3×4mL). The combined organic phases were dried over Na2SO4, and evaporated, in vacuo. The residue was purified by chromatography on a silica gel column (30×6cm). Elution with 1:1 to 2:3 hexanes-ethyl acetate gave 6a as pale yellow crystalline powder: yield 0.050g (87%);

Reference： [1]Zhu, Mei; Ma, Ling; Wen, Jiajia; Dong, Biao; Wang, Yujia; Wang, Zhen; Zhou, Jinming; Zhang, Guoning; Wang, Juxian; Guo, Ying; Liang, Chen; Cen, Shan; Wang, Yucheng [European Journal of Medicinal Chemistry, 2020, vol. 186]

65
[ 531-81-7 ]
[ 109-73-9 ]
N-(butyl)-2-oxo-2H-chromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With potassium hexafluorophosphate at 130℃; for 12h; Sealed tube; Green chemistry;
70%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: N-butylamine With dmap In dichloromethane at 20℃;	4.1.21 General procedure for the synthesis of coumarin derivatives 8a-g General procedure: 3-Carboxycoumarin 6 (1mmol) was dissolved in 10mL of dichloromethane and DCC (1mmol) was added to the mixture. The resulting reaction mixture was stirred for 1h at room temperature. Then appropriate amine 7a-g (1mmol) and DMAP (10mol%) were added sand stirring continued at room temperature for 3-4h. The progress of the reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was diluted with DCM (5mL) and solid formed was separated by filtration. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel (60-120 mesh) column chromatography using 1% MeOH in CHCl3 as eluent.

Reference： [1]Sonam, None; Shinde, Vikki N.; Kumar, Anil [Journal of Organic Chemistry, 2022, vol. 87, # 5, p. 2651 - 2661]
[2]Butcher, R. J.; Katiyar, Diksha; Sharma, Rajesh Kumar; Singh, Vineeta; Tiwari, Neha [Bioorganic Chemistry, 2020, vol. 98]

66
[ 531-81-7 ]
[ 124-22-1 ]
[ 1846-88-4 ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: n-Dodecylamine With dmap In dichloromethane at 20℃;	4.1.21 General procedure for the synthesis of coumarin derivatives 8a-g General procedure: 3-Carboxycoumarin 6 (1mmol) was dissolved in 10mL of dichloromethane and DCC (1mmol) was added to the mixture. The resulting reaction mixture was stirred for 1h at room temperature. Then appropriate amine 7a-g (1mmol) and DMAP (10mol%) were added sand stirring continued at room temperature for 3-4h. The progress of the reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was diluted with DCM (5mL) and solid formed was separated by filtration. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel (60-120 mesh) column chromatography using 1% MeOH in CHCl3 as eluent.

Reference： [1]Butcher, R. J.; Katiyar, Diksha; Sharma, Rajesh Kumar; Singh, Vineeta; Tiwari, Neha [Bioorganic Chemistry, 2020, vol. 98]

67
[ 531-81-7 ]
oleylamine [ No CAS ]
N-(octadec-9-en-1-yl)-2-oxo-2H-chromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: oleylamine With dmap In dichloromethane at 20℃;	4.1.21 General procedure for the synthesis of coumarin derivatives 8a-g General procedure: 3-Carboxycoumarin 6 (1mmol) was dissolved in 10mL of dichloromethane and DCC (1mmol) was added to the mixture. The resulting reaction mixture was stirred for 1h at room temperature. Then appropriate amine 7a-g (1mmol) and DMAP (10mol%) were added sand stirring continued at room temperature for 3-4h. The progress of the reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was diluted with DCM (5mL) and solid formed was separated by filtration. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel (60-120 mesh) column chromatography using 1% MeOH in CHCl3 as eluent.

Reference： [1]Butcher, R. J.; Katiyar, Diksha; Sharma, Rajesh Kumar; Singh, Vineeta; Tiwari, Neha [Bioorganic Chemistry, 2020, vol. 98]

68
[ 531-81-7 ]
[ 765-30-0 ]
N-(cyclopropyl)-2-oxo-2H-chromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: Cyclopropylamine With dmap In dichloromethane at 20℃;	4.1.21 General procedure for the synthesis of coumarin derivatives 8a-g General procedure: 3-Carboxycoumarin 6 (1mmol) was dissolved in 10mL of dichloromethane and DCC (1mmol) was added to the mixture. The resulting reaction mixture was stirred for 1h at room temperature. Then appropriate amine 7a-g (1mmol) and DMAP (10mol%) were added sand stirring continued at room temperature for 3-4h. The progress of the reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was diluted with DCM (5mL) and solid formed was separated by filtration. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel (60-120 mesh) column chromatography using 1% MeOH in CHCl3 as eluent.

Reference： [1]Butcher, R. J.; Katiyar, Diksha; Sharma, Rajesh Kumar; Singh, Vineeta; Tiwari, Neha [Bioorganic Chemistry, 2020, vol. 98]

69
[ 110-89-4 ]
[ 531-81-7 ]
[ 18144-51-9 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: piperidine With dmap In dichloromethane at 20℃;	4.1.21 General procedure for the synthesis of coumarin derivatives 8a-g General procedure: 3-Carboxycoumarin 6 (1mmol) was dissolved in 10mL of dichloromethane and DCC (1mmol) was added to the mixture. The resulting reaction mixture was stirred for 1h at room temperature. Then appropriate amine 7a-g (1mmol) and DMAP (10mol%) were added sand stirring continued at room temperature for 3-4h. The progress of the reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was diluted with DCM (5mL) and solid formed was separated by filtration. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel (60-120 mesh) column chromatography using 1% MeOH in CHCl3 as eluent.

Reference： [1]Butcher, R. J.; Katiyar, Diksha; Sharma, Rajesh Kumar; Singh, Vineeta; Tiwari, Neha [Bioorganic Chemistry, 2020, vol. 98]

70
[ 109-01-3 ]
[ 531-81-7 ]
[ 324067-20-1 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: 1-methyl-piperazine With dmap In dichloromethane at 20℃;	4.1.21 General procedure for the synthesis of coumarin derivatives 8a-g General procedure: 3-Carboxycoumarin 6 (1mmol) was dissolved in 10mL of dichloromethane and DCC (1mmol) was added to the mixture. The resulting reaction mixture was stirred for 1h at room temperature. Then appropriate amine 7a-g (1mmol) and DMAP (10mol%) were added sand stirring continued at room temperature for 3-4h. The progress of the reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was diluted with DCM (5mL) and solid formed was separated by filtration. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel (60-120 mesh) column chromatography using 1% MeOH in CHCl3 as eluent.

Reference： [1]Butcher, R. J.; Katiyar, Diksha; Sharma, Rajesh Kumar; Singh, Vineeta; Tiwari, Neha [Bioorganic Chemistry, 2020, vol. 98]

71
[ 3295-64-5 ]
[ 531-81-7 ]
4-(1,2,3,4-tetrahydroacridin-4-yl)chroman-2-one [ No CAS ]

Reference： [1]Organic Letters,2020,vol. 22,p. 2600 - 2605

72
[ 531-81-7 ]
[ 827-94-1 ]
N-(2,6-dibromo-4-nitrophenyl)-2-oxo-2H-chromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Stage #2: 2,6-dibromo-4-nitroaniline With triethylamine In dichloromethane at 20℃; for 12h;	4.1.3. Synthesis of 2-Oxo-N-substituted phenyl-2H-chromene-3-carboxamide (13a-13r) General procedure: To the coumarin-3-carboxylic acid (1.0 g) in 20 ml dry DCM was added EDCl-HCl (0.6 g), and HOBt (0.55 g). After stirring at RT for 30 min, the amine (1.1 equiv) was added followed by triethylamine (1 ml). The reaction mixture was stirred at RT for 12 h. The progress of the reaction was monitored by using TLC (ethyl acetate/n-hexane: 30:70). After completion of the reaction, the reaction mixture was diluted with DCM and washed with 1M HCl solution. The organic layer was separated and further treated with saturated sodium bicarbonate solution followed by brine solution. The organic layer was dried on sodium sulfate and concentrated by using rota-evaporator. The crude product was recrystallized in Dichloromethane: Pentane (2:8).

Reference： [1]Jadhav, Hemant R.; Jain, Priti; Wadhwa, Pankaj [Letters in drug design and discovery, 2020, vol. 17, # 4, p. 416 - 425]

73
[ 504-29-0 ]
[ 531-81-7 ]
[ 301817-95-8 ]

Yield	Reaction Conditions	Operation in experiment
66%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Stage #2: 2-aminopyridine With triethylamine In dichloromethane at 20℃; for 12h;	4.1.3. Synthesis of 2-Oxo-N-substituted phenyl-2H-chromene-3-carboxamide (13a-13r) General procedure: To the coumarin-3-carboxylic acid (1.0 g) in 20 ml dry DCM was added EDCl-HCl (0.6 g), and HOBt (0.55 g). After stirring at RT for 30 min, the amine (1.1 equiv) was added followed by triethylamine (1 ml). The reaction mixture was stirred at RT for 12 h. The progress of the reaction was monitored by using TLC (ethyl acetate/n-hexane: 30:70). After completion of the reaction, the reaction mixture was diluted with DCM and washed with 1M HCl solution. The organic layer was separated and further treated with saturated sodium bicarbonate solution followed by brine solution. The organic layer was dried on sodium sulfate and concentrated by using rota-evaporator. The crude product was recrystallized in Dichloromethane: Pentane (2:8).
26%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate In acetonitrile at 20℃;	3.2. General Synthetic Method for the Preparation of 2a-e General procedure: Coumarin derivatives 2a-e were synthesised by the adaptation of a previously reported procedurewith an additional step of deprotection for Boc-2e [20]. Coumarin-3-carboxylic acid (1 eq.), a selectedamine (1.1 eq.), and PyBOP (1 eq.) were stirred at room temperature in acetonitrile. Upon completion,the reaction was quenched with brine (30 mL/5 mmol of coumarin-3-carboxylic acid) and extractionwas conducted with dichloromethane (30 mL/5 mmol of coumarin-3-carboxylic acid). The organic layerwas then washed with 10% citric acid, then 10% NaHCO3, following water and brine. The organicresidues were dried over Na2SO4. Finally, the solvent was removed under vacuum. The residues weretriturated with ethyl acetate to give the desired product as a solid.

Reference： [1]Jadhav, Hemant R.; Jain, Priti; Wadhwa, Pankaj [Letters in drug design and discovery, 2020, vol. 17, # 4, p. 416 - 425]
[2]Bao, Lei; Cole, Ivan S.; Lan, Minbo; Qian, Bin; Reichman, Suzie M.; Trinchi, Adrian; Váradi, Linda; Wei, Gang [Molecules, 2019, vol. 24, # 19]

74
[ 531-81-7 ]
1-(2-aminoethyl)-3-methoxy-2-methylpyridin-4(1H)-one [ No CAS ]
N-(2-(2-methyl-3-hydroxy-1-(4H)-4-oxopyridinyl)ethyl)-2-oxo-2H-benzopyran-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93.1%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dmap; 2-mercaptothiazoline; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 24h; Stage #2: 1-(2-aminoethyl)-3-methoxy-2-methylpyridin-4(1H)-one In dichloromethane at 20℃; for 24h; Stage #3: With boron tribromide In dichloromethane at 0℃; for 12h; Inert atmosphere;	1 Add 3-carboxycoumarin (0.190g, 1mmol), dichloromethane (10mL), and then add dicyclohexylcarbodiimide (0.226g, 1.1mmol), 2-mercaptothiazoline ( 0.130 g, 1.1 mmol), 4-dimethylaminopyridine (5 mg, 0.04 mmol), reacted at room temperature for 24 hours, after the reaction, filtered, and the filtrate was concentrated for use.Add 1-(2-aminoethyl)-2-methyl-3-methoxypyridin-4-one (0.182g, 1mmol) and dichloromethane (10mL) into a 100mL single-neck flask, and add the above filtrate dropwise, React at room temperature for 24 hours. After the reaction is complete, the reaction solution is concentrated and purified by silica gel column chromatography (dichloromethane: methanol = 100:1-20:1 gradient elution) to obtain a white solid (0.237 g) with a yield of 66.9%.Add the above white solid (0.212g, 0.6mmol), anhydrous dichloromethane (10mL) to a 100mL single-neck flask, dissolve boron tribromide (0.601g, 2.4mmol) in anhydrous dichloromethane (10mL) and place Constant pressure dropping funnel, N2Protected, slowly add boron tribromide dropwise at 0°C, after dropping, warm to room temperature and react for 12h.The reaction was monitored by TLC. After the conversion of the raw materials was completed, methanol (10 mL) was added dropwise to quench the reaction. After the dripping was completed, the reaction solution was concentrated for 0.5 h and recrystallized with methanol/ether to obtain a white solid a1b1 (0.190g). Yield 93.1%.
	Multi-step reaction with 2 steps 1.1: dicyclohexyl-carbodiimide; 2-mercaptothiazoline; dmap / dichloromethane / 24 h / 20 °C 1.2: 24 h / 20 °C 2.1: boron tribromide / dichloromethane / 12 h / -48 - 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN110804045, 2020, A Location in patent: Paragraph 0062; 0068; 0069
[2]Bai, Renren; Gu, Jinping; Guo, Jianan; Jiang, Xiaoying; Lv, Yangjing; Mi, Zhisheng; Shi, Yuan; Xie, Yuanyuan; Yao, Chuansheng; Zhang, Changjun; Zhou, Tao [Bioorganic and medicinal chemistry, 2020, vol. 28, # 12]

75
[ 531-81-7 ]
1-(2-aminoethyl)-3-methoxy-2-methylpyridin-4(1H)-one [ No CAS ]
N-(2-(3-methoxy-2-methyl-4-oxopyridin-1(4H)-yl)ethyl)-2-oxo-2H-chromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dmap; 2-mercaptothiazoline; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 24h; Stage #2: 1-(2-aminoethyl)-3-methoxy-2-methylpyridin-4(1H)-one In dichloromethane at 20℃; for 24h;	4.1.10. General procedures for the preparation of compounds 17a-f and19a-w General procedure: To a vigorously stirred suspension of coumarin-3-carboxylic acids14a-g or 16a-r (1 mmol) in DCM (10 mL) were added DCC (0.226 g, 1.1mmol), 2-mercaptothiazoline (0.130 g, 1.1 mmol), and a catalyticamount of DMAP (5 mg) in sequence. The mixture was stirred for 24 hat room temperature, the white precipitate N,N’-dicyclohexylurea(DCU) filtered from the yellow solution, the filtrate added to the amine3a-c, 8a-b, 11a-b (1 mmol) dissolved in DCM (10 mL), and the reactionmixture allowed to stir 24 h. After the reaction was complete, the solventwas removed in vacuo. The residue was further purified by columnchromatography on silica gel (eluant: DCM:MeOH = 100:1-20:1 gradientelution) to afford 17a-f or 19a-w as yellow solids.

Reference： [1]Bai, Renren; Gu, Jinping; Guo, Jianan; Jiang, Xiaoying; Lv, Yangjing; Mi, Zhisheng; Shi, Yuan; Xie, Yuanyuan; Yao, Chuansheng; Zhang, Changjun; Zhou, Tao [Bioorganic and medicinal chemistry, 2020, vol. 28, # 12]

76
[ 531-81-7 ]
1-(2-aminoethyl)-5-methoxy-2-methylpyridin-4(1H)-one [ No CAS ]
N-(2-(5-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)ethyl)-2-oxo-2H-chromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87.3%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dmap; 2-mercaptothiazoline; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 24h; Stage #2: 1-(2-aminoethyl)-5-methoxy-2-methylpyridin-4(1H)-one In dichloromethane at 20℃; for 24h; Stage #3: With boron tribromide In dichloromethane at 0℃; for 12h; Inert atmosphere;	1 Add 3-carboxycoumarin (0.190g, 1mmol), dichloromethane (10mL), and then add dicyclohexylcarbodiimide (0.226g, 1.1mmol), 2-mercaptothiazoline ( 0.130 g, 1.1 mmol), 4-dimethylaminopyridine (5 mg, 0.04 mmol), reacted at room temperature for 24 hours, after the reaction, filtered, and the filtrate was concentrated for use.Add 1-(2-aminoethyl)-6-methyl-3-methoxypyridin-4-one (0.182g, 1mmol) and dichloromethane (10mL) into a 100mL single-neck flask, and add the above filtrate dropwise, React at room temperature for 24 hours. After the reaction is complete, the reaction solution is concentrated and purified by silica gel column chromatography (dichloromethane: methanol = 100:1-20:1 gradient elution) to obtain a white solid (0.115 g) with a yield of 32.5%.Add the above white solid (0.177g, 0.5mmol), anhydrous dichloromethane (10mL) to a 100mL single-neck flask, dissolve boron tribromide (0.463g, 1.85mmol) in anhydrous dichloromethane (10mL) and place Constant pressure dropping funnel, N2Protected, slowly add boron tribromide dropwise at 0°C, after dropping, warm to room temperature and react for 12h.The reaction was monitored by TLC. After the conversion of the raw materials was completed, methanol (10 mL) was added dropwise to quench the reaction. After the dripping was completed, the reaction solution was concentrated for 0.5 h and recrystallized with methanol/ether to obtain a white solid a1b2 (0.148g). Yield 87.3%.
	Multi-step reaction with 2 steps 1.1: dicyclohexyl-carbodiimide; 2-mercaptothiazoline; dmap / dichloromethane / 24 h / 20 °C 1.2: 24 h / 20 °C 2.1: boron tribromide / dichloromethane / 12 h / -48 - 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN110804045, 2020, A Location in patent: Paragraph 0073; 0080; 0081
[2]Bai, Renren; Gu, Jinping; Guo, Jianan; Jiang, Xiaoying; Lv, Yangjing; Mi, Zhisheng; Shi, Yuan; Xie, Yuanyuan; Yao, Chuansheng; Zhang, Changjun; Zhou, Tao [Bioorganic and medicinal chemistry, 2020, vol. 28, # 12]

77
[ 66775-80-2 ]
[ 531-81-7 ]
N-(2-(3-hydroxy-4-oxopyridin-1(4H)-yl)ethyl)-2-oxo-2Hchromene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93.9%	Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With dmap; 2-mercaptothiazoline; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 24h; Stage #2: 1-(2-aminoethyl)-3-methoxypyridin-4(1H)-one In dichloromethane at 20℃; for 24h; Stage #3: With boron tribromide In dichloromethane at 0℃; for 12h; Inert atmosphere;	3 Add 3-carboxycoumarin (0.190g, 1mmol), dichloromethane (10mL), and then add dicyclohexylcarbodiimide (0.226g, 1.1mmol), 2-mercaptothiazoline ( 0.130 g, 1.1 mmol), 4-dimethylaminopyridine (5 mg, 0.04 mmol), reacted at room temperature for 24 hours, after the reaction, filtered, and the filtrate was concentrated for use.Add 1-(2-aminoethyl)-6-methyl-3-methoxypyridin-4-one (0.168g, 1mmol) and dichloromethane (10mL) into a 100mL single-neck flask, and add the above filtrate dropwise, React at room temperature for 24 hours. After the reaction is completed, the reaction solution is concentrated and purified by silica gel column chromatography (dichloromethane: methanol = 100:1-20:1 gradient elution) to obtain a white solid (0.183 g) with a yield of 53.8%.Add the above white solid (0.102g, 0.3mmol), anhydrous dichloromethane (10mL) to a 100mL single-neck flask, dissolve boron tribromide (0.375g, 1.5mmol) in anhydrous dichloromethane (10mL) and place Constant pressure dropping funnel, N2Protected, slowly add boron tribromide dropwise at 0°C, after dropping, warm to room temperature and react for 12h.The reaction was monitored by TLC. After the conversion of the raw materials was completed, methanol (10 mL) was added dropwise to quench the reaction. After the dripping was completed, the reaction solution was concentrated for 0.5 h and recrystallized with methanol/ether to obtain a white solid a1b3 (0.092g). Yield 93.9%.
	Multi-step reaction with 2 steps 1.1: dicyclohexyl-carbodiimide; 2-mercaptothiazoline; dmap / dichloromethane / 24 h / 20 °C 1.2: 24 h / 20 °C 2.1: boron tribromide / dichloromethane / 12 h / -48 - 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN110804045, 2020, A Location in patent: Paragraph 0085; 0093; 0094
[2]Bai, Renren; Gu, Jinping; Guo, Jianan; Jiang, Xiaoying; Lv, Yangjing; Mi, Zhisheng; Shi, Yuan; Xie, Yuanyuan; Yao, Chuansheng; Zhang, Changjun; Zhou, Tao [Bioorganic and medicinal chemistry, 2020, vol. 28, # 12]

78
[ 531-81-7 ]
[ 16179-97-8 ]
[ 1542158-09-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	With 4-methyl-morpholine In tetrahydrofuran at 20℃; for 20h; Sealed tube;	4.2. General Procedure General procedure: An ordinary screw-cap vial was charged with a magnetic stirring bar; the correspondingcoumarin-3-carboxylic acid 2 or chromone-3-carboxylic acid 3 (0.1 mmol, 1equivalent), THF (0.2 mL), N-methyl morpholine (0.17 mmol, 1.7 equivalent), and pyridylaceticacid hydrochloride 1 or 6 (0.15 mmol, 1.5 equivalent) was added. The reactionmixture was stirred at room temperature and monitored by 1H NMR spectroscopy. Afterthe complete consumption of the carboxylic acid 2a or 3a, the mixture was directly subjectedto FC on silica gel (n-hexane:ethyl acetate 3:1 or 2:1) to afford the pure products 4,5 or 7.The ultrasound variant of the reaction proceeded under the same reaction conditions,however without a stirring bar and with the shorter reaction time of 1.5 h.4-[(Pyridin-2-yl)methyl]-3,4-dihydro-2H-1-benzopyran-2-one (4a) pure product was isolatedby flash chromatography on silica gel (n-hexane:ethyl acetate-3:1) as colorless oilin over 98% yield following the regular procedure and 59% yield following the ultrasoundprocedure. 1H NMR (700 MHz, Chloroform-d) δ 8.60 (ddd, J = 4.8, 1.8, 0.9 Hz, 1H), 7.57(td, J = 7.6, 1.8 Hz, 1H), 7.27-7.23 (m, 1H), 7.17 (ddd, J = 7.5, 4.9, 1.1 Hz, 1H), 7.07 (d, J = 8.0Hz, 1H), 7.06-7.02 (m, 2H), 6.96 (d, J = 7.7 Hz, 1H), 3.68 (dddd, J = 8.8, 6.9, 5.9, 3.7 Hz, 1H),3.11 (dd, J = 13.8, 6.9 Hz, 1H), 2.94 (dd, J = 13.8, 8.8 Hz, 1H), 2.79 (dd, J = 16.0, 5.9 Hz, 1H),2.73 (dd, J = 16.0, 3.7 Hz, 1H). 13C NMR (176 MHz, Chloroform-d) δ 168.1, 157.9, 151.5,149.8, 136.7, 128.6, 127.8, 126.2, 124.5, 124.3, 122.0, 117.2, 43.2, 35.4, 34.2.

Reference： [1]Albrecht, Anna; Bojanowski, Jan [Molecules, 2021, vol. 26, # 15]

79
[ 531-81-7 ]
[ 6622-91-9 ]
4-[(pyridin-4-yl)methyl]-3,4-dihydro-2H-1-benzopyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With 4-methyl-morpholine In tetrahydrofuran at 20℃; for 1.5h; Sealed tube; Sonication;	4.2. General Procedure General procedure: An ordinary screw-cap vial was charged with a magnetic stirring bar; the correspondingcoumarin-3-carboxylic acid 2 or chromone-3-carboxylic acid 3 (0.1 mmol, 1equivalent), THF (0.2 mL), N-methyl morpholine (0.17 mmol, 1.7 equivalent), and pyridylaceticacid hydrochloride 1 or 6 (0.15 mmol, 1.5 equivalent) was added. The reactionmixture was stirred at room temperature and monitored by 1H NMR spectroscopy. Afterthe complete consumption of the carboxylic acid 2a or 3a, the mixture was directly subjectedto FC on silica gel (n-hexane:ethyl acetate 3:1 or 2:1) to afford the pure products 4,5 or 7.The ultrasound variant of the reaction proceeded under the same reaction conditions,however without a stirring bar and with the shorter reaction time of 1.5 h.

Reference： [1]Albrecht, Anna; Bojanowski, Jan [Molecules, 2021, vol. 26, # 15]

80
[ 531-81-7 ]
[ 16738-00-4 ]
N’-(2-(4-bromophenoxy)acetyl)-2-oxo-2H-chromene-3-carbohydrazide [ No CAS ]