Name: 496-41-3|Benzofuran-2-carboxylic acid|98%
Brand: Ambeed
SKU: A315071
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1
[ 54008-77-4 ]
[ 496-41-3 ]

Reference： [1]Journal of the American Chemical Society,1948,vol. 70,p. 1655

2
[ 59214-70-9 ]
[ 109-72-8 ]
[ 60-29-7 ]
[ 496-41-3 ]

Reference： [1]Journal of the American Chemical Society,1948,vol. 70,p. 1655

3
[ 1646-26-0 ]
[ 496-41-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	With Oxone; trifluoroacetic acid In 1,4-dioxane for 10h; Reflux; Green chemistry;	Benzoic Acid (3a); Typical Procedure from Acetophenone or Phenylacetylene General procedure: To a mixture of acetophenone (100 mg, 1 equiv) or phenylacetylene (1 equiv) in dioxane (5 mL), Oxone (2 equiv) and TFA (2 equiv) were added. The mixture was then heated to reflux for 10 h and then cooled to r.t. H2O (10 mL) was added and the mixture was extracted with EtOAc (2 × 20 mL). The combined organic layers were treated with sat. NaHCO3 solution and the aqueous layer was poured onto crushed ice and treated with 2 M HCl; a colorless solid precipitated out. The precipitate was filtered off and dried in vacuo to give benzoic acid (3a) after column chromatography (silica gel; EtOAc-hexane, 1:9) as a white crystalline solid; yield: 0.096 g (95%) from 1a; mp 122-123 °C.
	With potassium permanganate
	With alkaline aqueous sodium hypochlorite solution

Reference： [1]Aravinda Kumar; Venkateswarlu, Vunnam; Vishwakarma, Ram A.; Sawant, Sanghapal D. [Synthesis, 2015, vol. 47, # 20, p. 3161 - 3168]
[2]Stoermer [Chemische Berichte, 1897, vol. 30, p. 1711]
[3]Farrar; Levine [Journal of the American Chemical Society, 1950, vol. 72, p. 4433,4435]

4
[ 67-56-1 ]
[ 496-41-3 ]
[ 1646-27-1 ]

Yield	Reaction Conditions	Operation in experiment
82%	With thionyl chloride; at 40℃; for 6h;	Compound benzofuran-2-carboxylic acid (0901-135) (1.0 g, 6.1 mmol, 1.0 equiv)Dissolved in 50 ml of methanol.The ice bath was cooled and thionyl chloride (1.3 mL, 18.3 mmol, 3.0 equiv) was slowly added dropwise.The mixture was stirred at 40 C for 6 hours.After completion of the reaction, the mixture was concentrated under reduced pressure, and the residue was dissolved in methylene chloride. Saturated sodium hydrogen carbonate solution was added and the mixture was made basic and liquid-separated.The organic phase was dried over anhydrous sodium sulfate, spin-dried, and the residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 10/1) to give the product methyl benzofuran-2-carboxylate ( 900 mg, yield: 82%).

Reference： [1]Patent: CN107383024,2017,A .Location in patent: Paragraph 0401
[2]Bollettino Scientifico della Facolta di Chimica Industriale di Bologna,1952,vol. 10,p. 168

5
[ 496-41-3 ]
[ 64-17-5 ]
[ 3199-61-9 ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 7973 - 7978
[2]Chemische Berichte,1886,vol. 19,p. 2399
[3]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1988,vol. 27,p. 524 - 526
[4]Journal of Medicinal Chemistry,2013,vol. 56,p. 437 - 450
[5]Medicinal Chemistry Research,2014,vol. 23,p. 2080 - 2092

6
[ 496-41-3 ]
[ 55038-01-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	With lithium aluminium tetrahydride In diethyl ether at 20℃; for 10h;
80%	With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere;
80%	With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	2.9. Typical procedure for the preparation of benzofuran-2-ylmethanols: synthesis of the benzofuran-2-ylmethanol In a flame dried two-necked round bottom flask charged with a stir bar, LiAlH4 in THF (2 M, 3.4 mL, 6.79 mmol, 1.1 equiv.) was added dropwise to a solution of benzofuran-2-carboxylic acid (1.0 g, 6.17 mmol, 1.0 equiv.) in anhydrous THF (20 mL) at 0°C under argon. The mixture was allowed to warm to room temperature and stirred for 2 hours. After the complete consumption of the starting material (TLC, hexane/EtOAc 90/10 v/v), the reaction was cooled down to 0°C and quenched by slow addition of an 80 percent aqueous MeOH solution. The mixture was extracted with AcOEt, washed with brine and the combined organic phase was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by chromatography on SiO2 (25-40 μm), eluting with a 85/15 (v/v) n-hexane/AcOEt mixture (Rf = 0.24) to afford 0.713 g of benzofuran-2-ylmethanol as a pale yellow oil (0.713 g, 80% yield).

	With lithium aluminium tetrahydride; diethyl ether
	With lithium aluminium tetrahydride In diethyl ether
	Multi-step reaction with 6 steps 1: thionyl chloride 2: diethyl ether; pyridine 3: aqueous hydrochloric acid 4: aqueous KOH-solution 5: aniline / anschliessend erhitzen mit wss. Salzsaeure 6: aqueous KOH-solution
	Multi-step reaction with 5 steps 1: thionyl chloride 2: diethyl ether; pyridine 3: aqueous hydrochloric acid 4: aniline / anschliessend erhitzen mit wss. Salzsaeure 5: aqueous KOH-solution
	Multi-step reaction with 4 steps 1: thionyl chloride 2: diethyl ether; pyridine 3: aqueous acetic acid; zinc / anschliessend erwaermen mit wss. Kaliumcarbonat-Loesung 4: aqueous KOH-solution
	In tetrahydrofuran; diethyl ether; water	35.a a a 1-Benzofuran-2-ylmethanol Lithium aluminium hydride (467 mg, 12.3 mmol) was suspended in diethyl ether and the suspension was heated under reflux. The suspension was added dropwise with 1-benzofurane-2-carboxylic acid (2.00 g, 12.3 mmol), dissolved in tetrahydrofuran (10 ml) and further heated under reflux for 20 minutes. The reaction mixture was cooled to 0° C., and then added with water (0.8ml) and stirred at the same temperature for 30 minutes. Insoluble solids were removed by filtration using Celite, and then the solvent was evaporated under reduced pressure to obtain the title compound as yellow oil (1.72 g, yield: 94%). 1H-NMR(CDCl3): 7.54-7.58(1H,m), 7.45-7.49(1H,m), 7.19-7.32(2H,m), 6.67(1H,s), 4.78(2H,d,J=4.5), 1.94(1H,brs)
	With sodium hydroxide; magnesium sulfate In diethyl ether; water	57.a a) a) Benzofuran-2-methanol Benzofuran-2-carboxylic acid (4.59 g., 28.3 mmol) as a solution in dry ethyl ether (100 mL) was added dropwise over 15 minutes to a suspension of lithium aluminum hydride (4.3 g., 113 mmol) in ethyl ether (180 mL) at 0° C. The reaction mixture was stirred for 2 hours while warming to room temperature. After recooling to 0° C., 4.3 mL of water was added with extreme caution. Sodium hydroxide (4.3 mL, 15% in water) was then added followed by an additional 12.9 mL of water. Magnesium sulfate (about 10 g.) was added and the thick white suspension was stirred briskly for about 30 minutes. The suspension was filtered through silica gel and the filter cake was washed thoroughly with ethyl ether. The filtrate was concentrated and dried under high vacuum to afford 4.15 g. of the title A product as a light yellow oil.
3.58 g (78%)	With diborane In tetrahydrofuran; water	6.1 Step 1) Preparation of Benzofuran-2-methanol Step 1) Preparation of Benzofuran-2-methanol 1 Molar diborane in tetrahydrofuran (61.6 mL, 61.6 mmol) was added dropwise over 10 minutes to a stirred solution of benzofuran-2-carboxylic acid (5.00 g, 30.8 mmol) in tetrahydrofuran (50 mL) at 0° C. Stirring was continued at 0° C. for 30 minutes, then at room temperature for 18 hours. The reaction mixture was quenched carefully by slow addition of 1:1 tetrahydrofuran/water, and extracted with ether. The organic extracts were dried (MgSO4) and concentrated to afford 3.58 g (78%) of product as a colorless oil. 1 H NMR (DMSO-d6): δ7.57 (m, 2H, ArH), 7.27 (m, 2H, ArH), 6.75 (s, 1H, CH=C--), 4.58 (s, 2H, CH2 OH).
	With sulfuric acid; sodium hydrogencarbonate In tetrahydrofuran; ethanol	5 Synthesis of (benzofuran-2-yl)methanol Synthesis of (benzofuran-2-yl)methanol 2-Benzofurancarboxylic acid (2.43 g) was dissolved in ethanol (50 mL), and concentrated sulfuric acid (1 mL) was added thereto, followed by refluxing for four hours. After cooling of the mixture, ethanol was removed under reduced pressure, saturated sodium hydrogencarbonate solution was added thereto, followed by extraction with ether (250 mL). The extract was dried over magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified through silica gel column chromatography (silica gel (30 g), eluent; hexane: ethyl acetate = 5:1), to thereby yield 2.72 g of an ethyl ester (yield 95.4%). The ethyl ester (2.72 g) was dissolved in THF (30 mL), and lithium aluminum hydride (0.54 g) was added thereto. The atmosphere was purged with nitrogen, the mixture was stirred for 30 minutes at room temperature. The reaction mixture was diluted with ether (100 mL), and saturated sodium sulfate solution was added thereto, to thereby decompose the excessive reagent. The organic layer was separated through decantation, and the residue was washed twice with ether (50 mL). The organic layers were combined and dried over magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified through silica gel column chromatography (silica gel (20 g), eluent; hexane: ethyl acetate = 4:1), to thereby yield 1.95 g of the target alcohol compound (yield 92.0%). NMR δ ppm(CDCl3): 1.90(t, 1H, J=6.5Hz), 4.78(d, 2H, J=6.5Hz), 6.67(s, 1H), 7.18-7.32(m, 2H), 7.47(d, 1H, J=8.4Hz), 7.55(dd, 1H, J=6.5, 1.1Hz)
	Multi-step reaction with 2 steps 1.1: chloroformic acid ethyl ester; triethylamine / dichloromethane / 1 h / 0 °C 1.2: 0 - 23 °C 2.1: sodium hydride; zinc(II) iodide; sodium iodide / tetrahydrofuran; mineral oil / 7 h / 40 °C / Sealed tube
	With D-Glucose; Bacillus subtilis glucose dehydrogenase; Segniliparus rugosus carboxylic acid reductase; nicotinamide adenine dinucleotide phosphate; dimethyl sulfoxide; ATP; magnesium chloride In aq. phosphate buffer at 30℃; for 18h; Enzymatic reaction;
	With D-Glucose; Escherichia coli endogenous alcohol dehydrogenase; Segniliparus rugosus carboxylic acid reductase; dimethyl sulfoxide; magnesium chloride In aq. phosphate buffer at 30℃; for 18h; Enzymatic reaction;

Reference： [1]Tseng, Pen-Wen; Yeh, Su-Wen; Chou, Chin-Hsing [Journal of Organic Chemistry, 2008, vol. 73, # 9, p. 3481 - 3485]
[2]Arcadi, Antonio; Fabrizi, Giancarlo; Fochetti, Andrea; Ghirga, Francesca; Goggiamani, Antonella; Iazzetti, Antonia; Marrone, Federico; Mazzoccanti, Giulia; Serraiocco, Andrea [RSC Advances, 2020, vol. 11, # 2, p. 909 - 917]
[3]Arcadi, Antonio; Calcaterra, Andrea; Chiarini, Marco; Fabrizi, Giancarlo; Fochetti, Andrea; Goggiamani, Antonella; Iazzetti, Antonia; Marrone, Federico; Marsicano, Vincenzo; Serraiocco, Andrea [Synthesis, 2021, vol. 54, # 3, p. 741 - 753]
[4]Gaertner [Journal of the American Chemical Society, 1951, vol. 73, p. 4400,4403]
[5]Mouysset; Bellan; Payard; Tisne-Versailles [Farmaco, Edizione Pratica, 1987, vol. 42, # 11, p. 805 - 813]
[6]Reichstein; Reichstein [Helvetica Chimica Acta, 1930, vol. 13, p. 1275,1280]
[7]Reichstein; Reichstein [Helvetica Chimica Acta, 1930, vol. 13, p. 1275,1280]
[8]Reichstein; Reichstein [Helvetica Chimica Acta, 1930, vol. 13, p. 1275,1280]
[9]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - US2003/212094, 2003, A1
[10]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US5223516, 1993, A
[11]Current Patent Assignee: PFIZER INC - US5084463, 1992, A
[12]Current Patent Assignee: POLA ORBIS HOLDINGS INC - EP1346987, 2003, A1
[13]Ong, Derek Yiren; Yen, Zhihao; Yoshii, Asami; Revillo Imbernon, Julia; Takita, Ryo; Chiba, Shunsuke [Angewandte Chemie - International Edition, 2019, vol. 58, # 15, p. 4992 - 4997][Angew. Chem., 2019, vol. 131, p. 5046 - 5051,6]
[14]Aleku, Godwin A.; Leys, David; Roberts, George W. [Green Chemistry, 2020, vol. 22, # 12, p. 3927 - 3939]
[15]Aleku, Godwin A.; Leys, David; Roberts, George W. [Green Chemistry, 2020, vol. 22, # 12, p. 3927 - 3939]

7
[ 496-41-3 ]
[ 41717-28-6 ]

Yield	Reaction Conditions	Operation in experiment
88%	With thionyl chloride; In dichloromethane; for 6h;Reflux;	General procedure: A mixture of the corresponding carboxylic acid (12.3mmol) and thionyl chloride (6 ml, 83 mmol) in 40 ml of dry dichloromethane (DCM) was stirred under reflux for 6 h. After cooling to room temperature, DCM and excess thionyl chloride were evaporated under reduced pressure. The residue was treated without further purification.
	With thionyl chloride; In benzene;	a) preparation of benzofuran-2-carbonyl chloride Thionyl chloride (12.5 ml) was added to a suspension of benzofuran-2-carboxylic acid (20 g) in anhydrous benzene (250 ml). The mixture was refluxed for 3 hours, then allowed to cool down to room temperature. Removal of the volatiles left the desired acid chloride (21.8 g, 98%).
	With thionyl chloride; N,N-dimethyl-formamide; at 45℃; for 0.5h;	SOCI2 (5 ml) and DMF (2 drops) were added to the carboxylic acid (3.08 mmol) and the mixture was stirred at 45C for 30 minutes. The excess of SOCI2 was removed under reduced pressure. Traces of SOCI2 were removed by distillation from DCM (2x5 ml). The acyl chloride was dissolved in DCM (5 ml) and added at O0C under nitrogen atmosphere to a stirred mixture of the amine (3.08 mmol) and Et3N (18.5 mmol) or DIEA (18.5 mmol) in DCM (5 ml). The mixture was stirred at O0C for 30 min and then allowed to warm up to room temperature. The reaction mixture was stirred at room temperature for a period of 30 minutes to 24 hours. The mixture was poured into water (100 ml) and extracted with DCM (3x100 ml). The combined organic phases were dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash chromatography, semi-preparative HPLC or recrystallization.

	With thionyl chloride; N,N-dimethyl-formamide; In dichloromethane; for 5h;Reflux;	The mixture of benzofuran-2-carboxalic acid (0.20 g, 1.23 mmol), SOCl2 (0.44 g, 3.70 mmol) and one drop DMF in CH2Cl2 (5 mL) was refluxed for 5 h. The crude product of benzofuran-2-carboxachloride was obtained after evaporation and directly used in the next step without further purification.
	With thionyl chloride; In chloroform; for 1h;Reflux;	SOCl2 (2.38g, 20mmol) was added drop-wise to a stirringsolution of 3-chlorobenzoic acid (6b, 0.78 g, 5 mmol) inCHCl3 (10 mL) under ice-water bath, and the mixture wasrefluxed for 1 h and then was concentrated under reducedpressure to get the intermediate.The intermediate in CHCl3 was added drop-wise to a stirringsolution of 1-(m-tolyl)piperazine hydrochloride (4b,0.53 g, 2.5 mmol) and TEA (10 mmol) in CHCl3 under icewaterbath. After being refluxed for 8h, the mixture waswashed with H2O and NaHCO3 saturated solution, then driedover Na2SO4 and concentrated under reduced pressure. Thecrude material was purified by CC (petroleum ether AcEt =4:1) and was acidulated with HCl and then was recrystallizedin EtOH to give the title compound 7c as white solid (0.30 g,34.19%)
	With thionyl chloride; In benzene; at 0℃; for 0.5h;	General procedure: To the solution of heterocyclic acid (1 mmol) in benzene at 0C was added SOCl2 (1.5 mmol) and reaction mixture was stirred for 30 min. Solvent was evaporated and heterocyclic acid chlorides obtained were used for next step without any purification.
	With thionyl chloride;Reflux;	Compound 9a (191 mg, 1 mmol) was refluxed in excess of thionylchloride (3 mL) overnight. Excess of thionyl chloride was evaporatedand the residue was dissolved in CH2Cl2, 3-bromopropylamine hydrobromide (328 mg, 1.5 mmol was addedfollowed by triethylamine (TEA; 0.42 mL, 3 mmol). The reactionmixture was stirred at room temperature. After the reaction wascompleted, the reaction mixture was diluted with CH2Cl2 andsequentially washed with water, 1 N HCl and saturated NaHCO3.The organic layer was dried over MgSO4, filtered and concentrated.The obtained product was purified by column chromatographywith n-hexane/ethyl acetate (EtOAc) = 4:1 to obtain 10a, (236 mg,76%) as white solid.
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0℃; for 3h;Inert atmosphere;	General procedure: The starting aryl carboxylic acid (1.0 equiv) was added as a 0.5 M solution in dry CH2Cl2 to a dry round-bottom flask charged with a stir bar under nitrogen atmosphere. The solution was then cooled to 0C. Catalytic DMF (few drops to 1mL) was then added. Oxalyl chloride (1.2 equiv) was added over 1min with stirring at 0C using a needle to vent into a balloon. After 15min, the reaction was allowed to warm to room temperature with continued stirring. Upon completion, the reaction was concentrated under reduced pressure; the generated acid chloride was re-dissolved in dry THF to make a 1M solution, and the solution was added slowly to the prepared enolate at-78C. The enolate was prepared by first adding MeOAc (1.05 equiv) to a dry flask charged with a stir bar under nitrogen. The flask was cooled down to-78C to which LHMDS (1M in THF, 2.10 equiv) was added dropwise and stirred for 45minat-78C. The reaction was monitored by TLC until complete conversion of the acid chloride was observed. Upon completion, the reaction was quenched with NH4Cl (aq) at-78C, extracted with EtOAc three times, dried over Na2SO4, and filtered through a celite plug. The combined organic layers were concentrated under reduced pressure and purified by flash chromatography on silica gel using EtOAc/Hexanes as the mobile phase.
	With thionyl chloride; for 2h;Reflux;	General procedure: Thionyl chloride (9 mL) was added to the carboxylic acid (1.0 equiv, 10.0 mmol) and the mixture wasrefluxed for 2 h. The solution was then concentrated in vacuo. An oven-dried round-bottomed flask(100 mL) equipped with a stir bar was charged with glutarimide (909.4 mg, 0.91 equiv, 8.04 mmol), acyl chloride (1.0 equiv, 8.84 mmol), 4-dimethylaminopyridine (DMAP, 280.4 mg, 0.25 equiv, 2.5mmol) and dichloromethane (50 mL). Triethylamine (typically, 2.0 equiv) was added dropwise to the reaction mixture with vigorous stirring at 0 C, and the reaction mixture was stirred overnight at room temperature. After the indicated time, the reaction mixture was diluted with Et2O (20 mL) and filtered.The organic layer was washed with HCl (1.0 N, 30 mL), brine (30 mL), dried, and concentrated. The residue was purified by recrystallization or chromatography on silica gel to afford the corresponding amide.
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃;Inert atmosphere; Sealed tube;	324.0 mg (2 mmol) of benzofuran-2-carboxylic acid was suspended in 5 mLs of methylene chloride. The flask was flushed with argon for 10 minutes before injection of 0.4 mL (4 mmol) oxalyl chloride. Two drops of dimethylformamide were injected and furious bubbling began. The sealed vessel was continuously flushed with argon and vented for 2 hours at room temperature. 10 mLs of sieve dried ethanol was slowly injected and allowed to stir for an additional hour. Volatiles were removed under vacuum and the crude intermediate was resuspended in 5 mLs ethanol. To this solution was added 250 mg (5 mmol) of hydrazine water salt. The reaction was refluxed for 3 hours to give the corresponding hydrazide. Volatiles were removed under vacuum and the product suspended in 10 mLs of ethanol. From here the reaction proceeded as described in Series 1 General Procedure to yield 369.1 mg of dry product (72% yield). ?H NMR (400 MHz, DMSO): 10.26 (d, J 6.0 Hz, 1H),7.78 (d, J 8.0 Hz, 1H), 7.66 (d, J 8.4 Hz, 1H), 7.54 (s, 1H), 7.49-7.45 (m, 1H), 7.36-7.32 (m, 1H), 5.16-5.13 (m, 1H), 2.84-2.79 (m, 2H), 1.48-1.41 (m, 2H), 1.39-1.33 (m, 2H), 0.90 (t, J= 7.2 Hz,3H); ?3CNMR(100MHz,DMSO): 157.7, 154.7, 148.7, 127.5, 127.2, 124.2, 123.1, 112.2, 109.6, 51.2, 30.2, 20.3, 14.4. [(m+H)/z = 233.25]. (2254) purity 98.8%, tR 11.53 mins.
	With thionyl chloride;Reflux;	General procedure: Compound 28a (191 mg, 1 mmol) was refluxed in excess of thionylchloride (3 mL) overnight. Excess of thionyl chloride was evaporatedand the residue was dissolved in CH2Cl2, 3-bromopropylamine hydrobromide(328 mg, 1.5 mmol was added followed by triethylamine (TEA;0.42 mL, 3 mmol). The reaction mixture was stirred at room temperature.After the reaction was completed, the reaction mixture was dilutedwith CH2Cl2 and sequentially washed with water, 1 N HCl and saturatedNaHCO3. The organic layer was dried over MgSO4, filtered and concentrated.The obtained product was purified by column chromatographywith n-hexane: Ethyl acetate (EtOAc)=4:1 to obtain 29a,(236 mg, 76%) as white solid.
	With thionyl chloride; for 0.25h;Heating / reflux;	2. Amide route (Scheme 2);The acid chlorides (R'COCI) required for this method can be prepared in various ways. Benzo[ib]furan-2-carbonyl chloride was synthesised by refluxing benzo[Jb]furan-2-carboxylic acid in thionyl chloride for 15 min, then removing the excess thionyl chloride in vacuo. In the case of indole-2-carbonyl chlorides, PCI5 (1.1 equiv.) was added to a slurry of the indole-2-carboxylic acid (1.0 equiv.) in ether (0.1 mol acid to 400 mL ether). After 16 h the solvent was removed in vacuo, ether was added and removed in vacuo (repeated twice) and this procedure was performed using chloroform to give the indole-2-carbonyl chloride which was used in the coupling step.; Example 2.1; 2-(1-Benzofuran-2-yl)-4(3W)-quinazolinone (C: R=H, R'=1-benzofuran-2-yl); The intermediate amide (E: R=H, R'=H) was synthesised by refluxing anthranilamide (2.22 g, 16.3 mmol) and 1-benzofuran-2-carbonyl chloride (from benzo[fo]furan-2-carboxylic acid, 2.79 g, 17.2 mmol) in pyridine (30 mL) for 0.5 h. The intermediate amide was refluxed in 5% aqueous KOH (40 mL)/EtOH (20 mL) for 0.5 h to give the product (3.56 g, 83%) as a solid. 1H NMR (DMSO-d6) S ppm 12.75 (bs, 1H), 8.17 (dd, 1H, J=7.9, 1.2 Hz), 8.08 (d, 1H, J=0.7 Hz), 7.73-7.89 (m, 4H), 7.56 (td, 1H, J=7.3, 1.2 Hz), 7.50 (ddd, 1H, J=8.3, 7.5, 1.2 Hz), 7.37 (td, 1H, J=7.5, 0.9 Hz). ACPI-MS Found: [M+H]+= 263.

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[2]Journal of Medicinal Chemistry,2003,vol. 46,p. 3822 - 3839
[3]Asian Journal of Chemistry,2014,vol. 26,p. 209 - 215
[4]Journal of Medicinal Chemistry,2013,vol. 56,p. 3783 - 3805
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[6]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 2187 - 2197
[7]Chemische Berichte,1901,vol. 34,p. 774
[8]Helvetica Chimica Acta,1930,vol. 13,p. 1275,1280
[9]Journal of the Chemical Society,1951,p. 824
[10]Tetrahedron Letters,1990,vol. 31,p. 4297 - 4300
[11]Chemistry of Heterocyclic Compounds,1987,vol. 23,p. 751 - 754
Khimiya Geterotsiklicheskikh Soedinenii,1987,p. 915 - 918
[12]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1988,vol. 27,p. 378 - 379
[13]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1988,vol. 27,p. 524 - 526
[14]Journal of the American Chemical Society,1993,vol. 115,p. 536 - 547
[15]Journal of the American Chemical Society,1992,vol. 114,p. 3346 - 3355
[16]European Journal of Medicinal Chemistry,1993,vol. 28,p. 943 - 948
[17]Il Farmaco,1998,vol. 53,p. 667 - 674
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[19]Angewandte Chemie - International Edition,2006,vol. 45,p. 5194 - 5197
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[22]Patent: US5310930,1994,A
[23]Patent: WO2006/66879,2006,A2 .Location in patent: Page/Page column 48
[24]Tetrahedron Letters,2004,vol. 45,p. 8931 - 8934
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[46]Patent: WO2018/71740,2018,A1 .Location in patent: Page/Page column 22; 23
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8
[ 496-41-3 ]
[ 1914-60-9 ]

Yield	Reaction Conditions	Operation in experiment
74%	With hydrogen;palladium 10% on activated carbon; In ethyl acetate; under 3361.55 - 3620.13 Torr; for 48h;	a) (R,S)-2,3-Dihydro-benzofuran-2-carboxylic acid (54a) Commercially available benzofuran-2-carboxylic acid (Aldrich Chemical Company) (27 g, 167.7 mmol) was dissolved in ethyl acetate (300 mL) and hydrogenated in the presence of 10% Pd/C (20 g) at 65-70 psi for 2 days. After filtration of the solution and evaporation of the solvent, a mixture of solvent (ethyl acetate-hexane, 1:6) was added to the residue. The title compound was obtained as a crystalline solid by filtration (20.23 g, 74%). m.p: 116-117 C.; 1H NMR (300 MHz, CDCl3) delta: 11.05 (brs, 1H), 7.17 (m, 2H), 6.91 (m, 2H), 5.24 (dd, 1H), 3.63 (dd, 1H), 3.42 (dd, 1H).
	With hydrogen; acetic acid;palladium hydroxide on carbon; at 60℃; under 4137.29 Torr; for 2h;	Preparation 10; 2,3-Dihydro-1-benzofuran-2-carboxylic acidA mixture of 1-benzofuran-2-carboxylic acid (40.0 g, 250.0 mmol) and palladium hydroxide (20 wt. % on carbon, 2.0 g) in acetic acid (400 ml) was heated at 60 C. under a hydrogen atmosphere (80 psi) for 2 h. The mixture was filtered to give a solution of the title compound (39.5 g) in acetic acid.1H-NMR (d6-DMSO): 3.19-3.23 (1H), 3.50-3.54 (1H), 5.16-5.20 (1H), 6.78-6.82 (2H), 7.09-7.12 (1H), 7.18-7.20 (1H)

Reference： [1]Patent: US2005/54630,2005,A1 .Location in patent: Page/Page column 42
[2]Justus Liebigs Annalen der Chemie,1883,vol. 216,p. 169
[3]Il Farmaco,1998,vol. 53,p. 764 - 772
[4]Patent: US2008/200540,2008,A1 .Location in patent: Page/Page column 18

9
[ 939-18-4 ]
[ 496-41-3 ]

Reference： [1]Journal of the Chemical Society,1871,vol. 24,p. 43
Zeitschrift fuer Chemie,1871,p. 178
[2]Journal of the Chemical Society,1924,vol. 125,p. 561

10
[ 186581-53-3 ]
[ 496-41-3 ]
[ 1646-27-1 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1983,vol. 56,p. 2762 - 2767

11
[ 5036-48-6 ]
[ 496-41-3 ]
[ 95059-48-6 ]

Yield	Reaction Conditions	Operation in experiment
71%	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In N,N-dimethyl-formamide at 20℃; for 2h;	N-(3,4-dimethoxyphenethyl)benzo[b]thiophene-2-carboxamide (7) General procedure: A solution of compound 4b (0.4 g, 2.25 mmol),compound 3 (0.45 g, 2.47 mmol), HBTU (1.01 g, 2.69 mmol) and Et3N (0.48 mL, 3.37 mmol) in DMF (10 mL) was stirred at room temperature for 2 h.Then, the mixture was diluted with water (100 mL), and extracted with EtOAc (50mL × 3). The combined organic layers were dried over MgSO4, concentrated and purified by silica gel column chromatography (CH2Cl2: MeOH = 100:2) to give compound 7 (0.63 g, 73%) as a yellow solid, mp: 93-96 C.
	With water; 1,1'-carbonyldiimidazole 1.) DMF, RT, 2 h, 2.) DMF, a) RT, 18-24 h, b) reflux, 3-6 h; Yield given. Multistep reaction;

Reference： [1]Chen, Wei; Dong, Guoqiang; He, Shipeng; Xu, Tianying; Wang, Xia; Liu, Na; Zhang, Wannian; Miao, Chaoyu; Sheng, Chunquan [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 3, p. 765 - 768]
[2]Press; Wright Jr.; Chan; Haug; Marsico; Tomcufcik [Journal of Medicinal Chemistry, 1987, vol. 30, # 6, p. 1036 - 1040]

12
[ 496-41-3 ]
[ 124-38-9 ]
[ 131-76-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: Benzofuran-2-carboxylic acid With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: carbon dioxide In tetrahydrofuran; hexane at -78 - 20℃;	30.1 Step-1: To a solution of diisopropyl amine (62.7 mL, 444 mmol) in THF (620 mL) was added n-BuLi (2.5 M in hexane, 185 mL, 444 mmol) dropwise at -78oC. The above solution was added to a solution of benzofuran-2-carboxylic acid (24.0 g, 148 mmol) in tetrahydrofuran (500 mL) dropwise at -78°C. The resulting mixture was stirred at -78°C for 1 h and dry ice (100 g) was added portion wise. The mixture was stirred at room temperature overnight and quenched with ice, diluted with 1 N hydrochloric acid (700 mL), extracted with ethyl acetate (700 mL X 3). The organic layer was dried and evaporated to give benzofuran-2,3-dicarboxylic acid (26.0 g, 85%) as white solid. (MS ESI -ve, 205.03 [M-H]).
	With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃;

Reference： [1]Current Patent Assignee: FLATLEY DISCOVERY LAB LLC - WO2021/113795, 2021, A1 Location in patent: Page/Page column 49; 50
[2]Costa, Ana M. B. S. R. C. S.; Dean, Francis M.; Jones, Michael A.; Varma, Rajender S. [Journal of the Chemical Society. Perkin transactions I, 1985, p. 799 - 808]

13
[ 496-41-3 ]
[ 174775-48-5 ]
5-[(Benzofuran-2-carbonyl)-amino]-benzofuran-2-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 232 - 239

14
[ 496-41-3 ]
[ 33094-66-5 ]
[ 64209-68-3 ]
[ 10242-12-3 ]

Reference： [1]Canadian Journal of Chemistry,1983,vol. 61,p. 2287 - 2290

15
[ 496-41-3 ]
[ 69227-70-9 ]
[ 69227-69-6 ]
[ 10242-12-3 ]

Reference： [1]Canadian Journal of Chemistry,1983,vol. 61,p. 2287 - 2290

16
[ 3199-61-9 ]
[ 496-41-3 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium hydroxide; In ethanol; water; for 2h;Reflux;	General procedure: To ethyl-1-benzofuran-2-carboxylate (2) (1mmol) containing ethanol was added water (2:1, 30mL) and otassium hydroxide (2mmol). The mixture refluxed for 2h. The reaction was monitored by thin layer chromatography. After completion of the reaction, the reaction mixture was decanted into ice water and extracted the ethyl acetate ayer to give target compounds 3a and 3b. 4.1.2.1. Benzofuran-2-carboxylic acid (3a) White crystal; yield: 85%; mp 190C [mp lit. 191-192C] [50]; 1H NMR (500MHz, DMSO-d6): 7.35 (t, J=7.5Hz, 1H, H5-benzofuran), 7.50 (t, J=7.5Hz, 1H, H6-benzofuran), 7.66 (s, 1H, H3-benzofuran), 7.69 (d, J=8.5Hz, 1H, H7-benzofuran), 7.79 (d, J=7.5Hz, H4-benzofuran), 13.5 (bs, 1H, -OH).
	With sodium hydroxide; In water; N,N-dimethyl-formamide; at 60℃; for 0.5h;	General procedure: To a solution of intermediates 3a-3q (1mmol) in 10ml DMF, 2.0mL of 20% sodium hydroxide solution was dropped at 60C to carry out the ester hydrolysis reaction for 30min. Afterwards, the mixture was cooled to room temperature, and the PH value of the solution was adjusted to 2 using 10% hydrochloric acid, then the mixture was extracted with ethyl acetate. The organic phase was combined and condensed by vacuum concentration to afford the crude product, which was purified by recrystallization to give the designed compounds (4a-4q).

Reference： [1]Bioorganic Chemistry,2018,vol. 80,p. 180 - 188
[2]Bulletin of the Chemical Society of Japan,1983,vol. 56,p. 2762 - 2767
[3]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 71 - 74
[4]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 4939 - 4946
[5]Journal of Medicinal Chemistry,2017,vol. 60,p. 1959 - 1970
[6]European Journal of Medicinal Chemistry,2020,vol. 190

17
[ 496-41-3 ]
[ 87571-88-8 ]
Benzofuran-2-carboxylic acid ((1R,3R,5S)-8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-amide; hydrochloride [ No CAS ]

Reference： [1]Arzneimittel-Forschung/Drug Research,1993,vol. 43,p. 913 - 918

18
[ 55038-01-2 ]
[ 496-41-3 ]

Yield	Reaction Conditions	Operation in experiment
75%	With chromium(VI) oxide; sulfuric acid In water; acetone

Reference： [1]Kundu, Nitya G.; Pal, Manojit; Mahanty, Jyan S.; De, Mahuya [Journal of the Chemical Society. Perkin transactions I, 1997, # 19, p. 2815 - 2820]

19
[ 939-18-4 ]
alcoholic KOH-solution [ No CAS ]
[ 496-41-3 ]

Reference： [1]Journal of the Chemical Society,1871,vol. 24,p. 43
Zeitschrift fuer Chemie,1871,p. 178

20
[ 939-18-4 ]
aqueous KOH-solution [ No CAS ]
[ 496-41-3 ]

Reference： [1]Journal of the Chemical Society,1871,vol. 24,p. 43
Zeitschrift fuer Chemie,1871,p. 178

21
[ 939-18-4 ]
Na₂SO₃-solution [ No CAS ]
[ 496-41-3 ]

Reference： [1]Journal of the Chemical Society,1924,vol. 125,p. 561

22
[ 496-41-3 ]
[ 198821-79-3 ]
benzofuran-2-carboxylic acid (3-methoxy-4-oxazol-5-yl-phenyl)-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 2879 - 2882

23
[ 496-41-3 ]
[ 13325-10-5 ]
[ 357616-15-0 ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: Benzofuran-2-carboxylic acid With 1-hydroxybenzotriazol-hydrate; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: 4-Aminobutanol In dichloromethane at 20℃;
97%	Stage #1: Benzofuran-2-carboxylic acid With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; Inert atmosphere; Stage #2: 4-Aminobutanol In dichloromethane at 20℃; Inert atmosphere;	1 N-[4-(1-Hydroxy)butyl]benzo[b]furan-2-carboxamide (5a). To a solution of 2-benzofurancarboxylic acid 4a (0.50 g, 3.08 mmol) in dry dichloromethane (10.0 mL), 1-hydroxybenzotriazole hydrate (HOBT) (0.46 g, 3.40 mmol) and 1,3-dicyclohexylcarbodiimide (0.70 g, 3.40 mmol) were added at 0° C. under argon; the suspension was warmed to room temperature and stirred for 1 h. Then 4-amino-1-butanol (0.28 mL, 3.08 mmol) was added and the mixture was stirred overnight at room temperature. The resulting suspension was filtered through Celite, washed with chloroform (3×10 mL) and the filtrate evaporated. The crude product was purified by means of flash chromatography (10% methanol in chloroform) to give 0.70 g (97%) of 5a as a white solid: mp (methanol) 95-96° C.; 1H NMR (CDCl3) δ 1.67 (m, 4H), 2.14 (br s, 1H), 3.53 (m, 2H), 3.73 (m, 2H), 6.89 (br s, 1H), 7.25-7.48 (m, 4H), 7.63 (d, 1H; J=7.7 Hz). Anal. (C13H15NO3) C, H, N.
	With 1,1'-carbonyldiimidazole In tetrahydrofuran

Reference： [1]Campiani, Giuseppe; Butini, Stefania; Trotta, Francesco; Fattorusso, Caterina; Catalanotti, Bruno; Aiello, Francesca; Gemma, Sandra; Nacci, Vito; Novellino, Ettore; Stark, Jennifer Ann; Cagnotto, Alfredo; Fumagalli, Elena; Carnovali, Francesco; Cervo, Luigi; Mennini, Tiziana [Journal of Medicinal Chemistry, 2003, vol. 46, # 18, p. 3822 - 3839]
[2]Current Patent Assignee: UNIVERSITA DEGLI STUDI DI SIENA - US2009/238761, 2009, A1 Location in patent: Page/Page column 25; 18
[3]Zou, Mu-Fa; Keck, Thomas M.; Kumar, Vivek; Donthamsetti, Prashant; Michino, Mayako; Burzynski, Caitlin; Schweppe, Catherine; Bonifazi, Alessandro; Free, R. Benjamin; Sibley, David R.; Janowsky, Aaron; Shi, Lei; Javitch, Jonathan A.; Newman, Amy Hauck [Journal of Medicinal Chemistry, 2016, vol. 59, # 7, p. 2973 - 2988]

24
[ 496-41-3 ]
[ 874-89-5 ]
[ 73918-56-6 ]
[ 31708-25-5 ]
benzofuran-2-carboxylic acid [2-(4-bromo-phenyl)-ethyl]-[4-(4-cyano-benzyl)-4H-[1,2,4]triazol-3-ylmethyl]-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 5407 - 5411

25
[ 496-41-3 ]
[ 86060-82-4 ]
[ 88574-06-5 ]
6-{(2S)-2-[(1-benzofuran-2-ylcarbonyl)amino]-6-[benzyloxycarbonylamino]hexanoylamino}hexanoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 3103 - 3106

26
[ 204316-36-9 ]
[ 496-41-3 ]
[ 88574-06-5 ]
6-{(2S)-2-[(1-benzofuran-2-ylcarbonyl)amino]-3-[benzyloxycarbonylamino]propanoylamino}hexanoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 3103 - 3106

27
[ 252049-08-4 ]
[ 496-41-3 ]
[ 88574-06-5 ]
6-{(2S)-2-[(1-benzofuran-2-ylcarbonyl)amino]-4-[benzyloxycarbonylamino]butanoylamino}hexanoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 3103 - 3106

28
2-(benzofuran-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane [ No CAS ]
[ 124-38-9 ]
[ 496-41-3 ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: 2-(benzofuran-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane; carbon dioxide With copper(l) iodide; 5,5-bis(4,5-dihydrooxazol-2-yl)nonane; cesium fluoride In N,N-dimethyl-formamide at 90℃; for 10h; Stage #2: With hydrogenchloride; water In N,N-dimethyl-formamide
67%	Stage #1: 2-(benzofuran-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane; carbon dioxide With potassium <i>tert</i>-butylate; silver(I) acetate; triphenylphosphine In 1,4-dioxane at 100℃; for 8h; Inert atmosphere; Autoclave; Stage #2: With hydrogenchloride In tetrahydrofuran; water Inert atmosphere;
59%	With 1,3-bis(bis(4-methoxyphenyl)phosphino)propane; cesium fluoride In 1,4-dioxane at 60℃;

Reference： [1]Takaya, Jun; Tadami, Satoshi; Ukai, Kazutoshi; Iwasawa, Nobuharu [Organic Letters, 2008, vol. 10, # 13, p. 2697 - 2700]
[2]Zhang, Xiao; Zhang, Wen-Zhen; Shi, Ling-Long; Guo, Chun-Xiao; Zhang, Ling-Ling; Lu, Xiao-Bing [Chemical Communications, 2012, vol. 48, # 50, p. 6292 - 6294]
[3]Ukai, Kazutoshi; Aoki, Masao; Takaya, Jun; Iwasawa, Nobuharu [Journal of the American Chemical Society, 2006, vol. 128, # 27, p. 8706 - 8707]

29
[ 496-41-3 ]
[ 3199-61-9 ]

Reference： [1]Angewandte Chemie - International Edition,2006,vol. 45,p. 5194 - 5197
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 9942 - 9959

30
[ 496-41-3 ]
[ 57153-50-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: Cu; quinoline / 240 °C 2.1: BuLi / diethyl ether 2.2: -10 °C

Reference： [1]Kennis, Ludo E.J.; Bischoff, Francois P.; Mertens, Carolus J.; Love, Christopher J.; Van den Keybus, Frans A.F.; Pieters, Serge; Braeken, Mirielle; Megens, Anton A.H.P.; Leysen, Josee E. [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 1, p. 71 - 74]

31
[ 496-41-3 ]
[ 62119-70-4 ]

Reference： [1]Journal of the American Chemical Society,1951,vol. 73,p. 4400,4403
[2]Helvetica Chimica Acta,1930,vol. 13,p. 1275,1280
[3]Helvetica Chimica Acta,1930,vol. 13,p. 1275,1280

32
[ 496-41-3 ]
[ 4265-25-2 ]

Reference： [1]Journal of the American Chemical Society,1951,vol. 73,p. 4400,4403

33
[ 496-41-3 ]
[ 620628-32-2 ]
[ 620628-33-3 ]

Yield	Reaction Conditions	Operation in experiment
85%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1h;	9.D To compound 9C (47mg, 0.129 mmol) dissolved in DMF (1.5 mL) was added 2- Benzofuran carboxylic acid (21mg, 0.129 mmol), BOP reagent (57mg, 0.129 mmol) and DIEA (34, uL, 25 mg, 0.193 mmol). The reaction mixture was stirred at RT for 1 h, the solvent removed under vacuum, and the crude product purified by column chromatography using silica gel (eluent 25% EtOAc: hexanes). The solvent was removed under vacuum to afford 9D (56 mg, 85%), as a clear film (M+H=509.15)

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2003/91252, 2003, A1 Location in patent: Page/Page column 56

34
[ 496-41-3 ]
[ 280551-95-3 ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium fluoride; Selectfluor In water; 1,2-dichloro-ethane at 70℃;
75%	With potassium fluoride; selectfluor II In water; 1,2-dichloro-ethane at 70℃; for 15h; Sealed tube;	1 Example 1Synthesis and Separation of 2-Fluorobenzofuran: In a 50 mL round bottom flask equipped with a magnetic stirrer,Benzofuran-2-carboxylic acid (162 mg, 1.0 mmol, 1.0 eq),Selectfluor (708 mg, 2.0 mmol, 2.0 eq), potassium fluoride(232 mg, 4.0 mmol, 4.0 eq); then dichloroethane (3.3 mL) and water (1.7 mL) were added as solvent;The reaction bottle was sealed in an oil bath at 70 ° C and heated and stirred for 15 hours. After the reaction was completed,The reaction mixture was extracted twice with 20 mL of ether. The organic phase was combined and washed with saturated brine and then dried over anhydrous sodium sulfate. After drying,Solvent to give the crude product; the crude product was subjected to column separation using analytically pure n-pentane as eluent to give the final productThe 2-fluorobenzofuran was a yellow oily liquid in 75% yield.
	With sodium hydrogencarbonate; Selectfluor In water; pentane at 20℃; for 1h;	11.a Chloromethyl-4-fluoro-1, 4-diazobicyclo [2.2. 2] octane bis-(tetrafluoroborate ("SelectfluorNo.") (13.11 g, 37.01 mmol) was added to a mixture of benzofuran-2-carboxylic acid (5. 0 g, 30.84 mmol) and sodium bicarbonate (6.22 g, 74.0 mmol) stirred in 70 mL of pentane/water (2: 5 by volume) at room temperature. After lhour at the pentane layer containing 2- fluorobenzofuran was separated from the mixture, and the water layer was extracted with pentane. The combined organic extract was dried through MgS04, and then the solvent was evaporated to give 2-fluorobenzofuran (1.70 g) as a yellow oil. The 2-fluorobenzofuran (850 mg, 6.24 mmol) and potassium acetate (1.29 g, 13.11 mL) were stirred in of chloroform (3.5 mL) at room temperature, and a solution of bromine (2.05 g, 12.80 mmol) in of chloroform (1 mL), and added slowly into the reaction mixture. After stirring for 1 h at room temperature, the mixture was washed with 5% NaHSO3 then brine, dried through MgS04, and the solvent was evaporated to give trans-2-fluoro-3-hydro-2, 3-dibromo-benzofuran as a light-brown oil (1.70 g). trans-2-Fluoro-3-hydro-2, 3-dibromo-benzofuran (1.66 g, 5.62 mmol) was dissolved in anhydrous ethanol (11 mL), and sodium ethoxide (420 mg, 6.18 mmol) was added. The mixture was stirred at RT for 5 min then brine was added, and the solution was extracted with pentane. The pentane layer was washed with water and with brine, dried through MgS04, and then the solvent was evaporated to give 3-bromo-2-fluorobenzofuran as a light-brown oil (950 mg). Under nitrogen, 3-bromo-2-fluorobenzofuran (465 mg, 2.16 mmol) was dissolved in anhydrous ether (5 mL), and stirred at-78 oC under nitrogen. n-Butyllithium (1.6M, 1.50 mL, 2.38 mmol) was added followed after 5 min by triethylstannyl bromide (680 mg, 2.38 mmol). The mixture was then allowed to warm to room temperature and stirring was continued for a further 1 h. The mixture was quenched, and washed with 1N sodium hydroxide, dried through MgS04, and then the solvent was evaporated to give the sub-title compound as a brown oil (370 mg), which was used directly without further purification for the next step.

Reference： [1]Yuan, Xi; Yao, Jian-Fei; Tang, Zhen-Yu [Organic Letters, 2017, vol. 19, # 6, p. 1410 - 1413]
[2]Current Patent Assignee: CENTRAL SOUTH UNIVERSITY - CN106397377, 2017, A Location in patent: Paragraph 0054; 0055; 0056; 0057; 0058
[3]Current Patent Assignee: ASTRAZENECA PLC - WO2003/87102, 2003, A1 Location in patent: Page/Page column 21-22

35
[ 496-41-3 ]
[ 1646-27-1 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; In methanol;	Synthesis of methyl 2-benzofurancarboxylate After adding thionyl chloride (3.80 ml) to a solution of 2-benzofurancarboxylic acid (2.00 g) in MeOH (60 ml) at -40 C., the mixture was stirred for 19 hours while the temperature gradually increased to room temperature. The reaction solution was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (n-hexane/AcOEt=6/1) to obtain methyl 2-benzofurancarboxylate. Yield: 2.16 g (y. 99.2%) 1H NMR(delta ppm, CDCl3): 3.99(s, 3H), 7.28 to 7.50(m, 2H), 7.54(s, 1H), 7.60(d, J=8.9 Hz, 1H), 7.69(d, J=7.6 Hz, 1H)

Reference： [1]Patent: US6589984,2003,B1

36
[ 496-41-3 ]
[ 7732-18-5 ]
[ 55038-01-2 ]

Yield	Reaction Conditions	Operation in experiment
3.58 g (78%)	With diborane In tetrahydrofuran	6.1 Step 1) Preparation of Benzofuran-2-methanol Step 1) Preparation of Benzofuran-2-methanol 1 Molar diborane in tetrahydrofuran (61.6 mL, 61.6 mmol) was added dropwise over 10 minutes to a stirred solution of benzofuran-2-carboxylic acid (5.00 g, 30.8 mmol) in tetrahydrofuran (50 mL) at 0° C. Stirring was continued at 0° C. for 30 minutes, then at room temperature for 18 hours. The reaction mixture was quenched carefully by slow addition of 1:1 THF/H2 O, and extracted with ether. The organic extracts were dried (MgSO4) and concentrated to afford 3.58 g (78%) of product as a colorless oil. 1 H NMR (DMSO-d6): δ7.57 (m, 2H, ArH), 7.27 (m, 2H, ArH), 6.75 (s, 1H, CH=C--), 4.58 (s, 2H, CH2 OH).

Reference： [1]Current Patent Assignee: PFIZER INC - US5104892, 1992, A

37
[ 496-41-3 ]
[ 115951-16-1 ]
benzofuran-2-carboxylic acid {1-[(4S,7R)-7-methyl-3-oxo-1-(pyridine-2-sulfonyl)-azepan-4-ylcarbamoyl]-cyclohexyl}-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 34 Preparation of Benzofuran-2-carboxylic acid {1-[(4S,7R)-7-methyl-3-oxo-1-(pyridine-2-sulfonyl)-azepan-4-ylcarbamoyl]-cyclohexyl}-amide Following the procedure of Example 12 (a-m), except substituting "N-Boc-amino-cyclohexane carboxylic acid" for "Boc-L-leucine" and "benzofuran-2-carboxylic acid" for "quinoline-6-carboxylic acid" gave the title compound: 1H NMR: 8.74-8.73 (s, 1H), 8.02-7.91(m, 2H), 7.71-7.69(d, 1H), 7.58-7.28(m, 6H), 6.73(s, 1H) 5.10-5.08(m, 1H), 4.78-4.73(d,1H), 4.44-4.13(m, 1H), 3.86-3.81(d, 1H), 2.33-2.01 (m, 6H), 1.98-1.40(m,8H), 0.99-0.97(d, 3H); Electrospray mass spec: M+H+=553.4.

Reference： [1]Patent: US2004/44201,2004,A1

38
[ 6066-82-6 ]
[ 496-41-3 ]
[ 861848-46-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 5 - 25℃; for 9.05h;	1; 4 Preparation of the Succinate Ester 4-3.; Charged a 2 L 3-necked flask equipped with magnetic stirrer bar, thermometer, and nitrogen inlet with benzofuran 2-carboxylic acid (100 g), N-hydroxysuccimide (78.2 g, 1.1 equiv) and N,N-dimethylformamide (620 ml). Stirred and cooled the suspension with an ice bath to 5° C. Added EDC.HCl (142 g, 1.2 equiv) portionwise (3 portions, add every 1 minute). The temperature increased by 20° C. during addition. Removed the ice bath, and stirred the suspension at 25° C. for 9 h. Cooled the solution with an ice bath, and poured it into water (1.5 L). Extracted with ethyl acetate (1.5 L, 500 ml), and washed the combined organic layers with water (2×500 ml) and saturated NaCl aqueous solution (500 ml). Removed the solvent under reduced pressure to afford a yellow solid. Treated the solid with ethyl acetate (40 ml), t-butyl methyl ether (200 ml) and isopropyl ether (200 ml). Filtered under reduced pressure, and washed the solid with iPr2O (50 ml). Dried the solid under vacuum at 40° C. for 4 h to give a pale yellow solid (136 g, 85%). 1H NMR (400 MHz, CDCl3) δ 7.86 (s, 1H), 7.77 (dd, 1H, J=7.9, 0.5 Hz), 7.65 (d, 1H, J=8.5 Hz), 7.56 (td, 1H, J=7.2, 1.2 Hz), 7.39 (dd, 1H, J=7.9, 7.3 Hz), 2.95 (s, 4H).

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2008/262224, 2008, A1 Location in patent: Page/Page column 8; 12-13

39
[ 496-41-3 ]
[ 849425-49-6 ]
[ 849425-50-9 ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: [(S)-1-(8-hydroxy-5,13-dioxo-5,8,9,10,11,13-hexahydro-7H-[1,2]diazepino[1,2-b]phthalazin-9-ylcarbamoyl)-3-methyl-butyl]-carbamic acid tert-butyl ester With hydrogenchloride In 1,4-dioxane; methanol at 20℃; for 1h; Stage #2: Benzofuran-2-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	1.g 4M HC1 in dioxane (1 ml, 4 mmol) was added to a solution of [ (S)-1- (8-hydroxy- 5, 13-dioxo-5, 8,9, 10, 11, 13-hexahydro-7H- [1, 2] diazepino [1, 2-b] phthalazin-9-ylcarbamoyl) - 3-methyl-butyl] -carbamic acid tert-butyl ester (129 mg, 0.272 mmol) in MeOH (1 ml) at RT. The reaction mixture was stirred for 1 hr at RT, then was concentrated under the reduced pressure. After drying under the vacuum, the residue was dissolved in DMF (2 ml) followed by the addition of benzofuran-2-carboxylic acid (54 mg, 0.33 mmol), 1- hydroxybenzotriazole (47 mg, 0.35 mmol), 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide HC1 (67 mg, 0.35 mmol), and N, N diisopropylethylamine (0.12 ml, 0.66 mmol). The reaction mixture was stirred for overnight at rt, then was diluted with EtOAc (50 ml), washed with cold IN HC1 (30 ml), sat'd NaHCO3 (30 ml), and brine (30 ml), dried over magnesium sulfate, filtered, concentrated iii vacuo by rotary evaporation, and chromatographed on silica gel (50% to 90% EtOAc/hexane) to yield the title compound (131 mg, 94% for two steps) ; LCMS (MH+) : 519.2

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2005/34838, 2005, A2 Location in patent: Page/Page column 21-22; 25

40
[ 633294-97-0 ]
[ 496-41-3 ]
benzofuran-2-carboxylic acid [(S)-1-((6S,7S,9aR)-6-hydroxy-3-oxo-octahydro-pyrrolo[1,2-a]azepin-7-ylcarbamoyl)-3-methyl-butyl]-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	Stage #1: [(S)-1-((6S,7S,9aR)-6-hydroxy-3-oxo-octahydro-pyrrolo[1,2-a] azepin-7-ylcarbamoyl)-3-methyl-butyl]-carbamic acid tert-butyl ester With trifluoroacetic acid In dichloromethane at 20℃; for 1h; Stage #2: Benzofuran-2-carboxylic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In DMF (N,N-dimethyl-formamide) at 20℃;	1h 1h. Benzofuran-2-carboxylic acid [(S)-1-((6S,7S,9aR)-6-hydroxy-3-oxo-octahydro-pyrrolo [1,2-a] azepin-7-ylcarbamoyl)-3-methyl-butyl]-amide Trifluoroacetic acid (2 ml) was added to a solution of (S)-1-((6S,7S,9aR)-6- hydroxy-3-oxo-octahydro-pyrrolo[1,2-a]azepin-7-ylcarbamoyl)-3-methyl-butyl]-carbamic acid tert-butyl ester (158 mg, 0.4 mmol) in CH2Cl2 (2 ml) at rt. The reaction mixture was stirred for 1 hr at rt, then was concentrated under the reduced pressure. After drying under the vacuum, the residue was dissolved in DMF (3 ml) followed by the addition of benzofuran-2-carboxylic acid (76 mg, 0.47 mmol), hydroxybenztriazole (69 mg, 0.51 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCl (97 mg, 0.51 mmol), and diisopropylethylamine (0.18 ml, 1.03 mmol). The reaction mixture was stirred for overnight at rt, and DMF was removed under the reduced pressure, then was diluted with EtOAc (70 ml), washed with cold 1N HCl (50 ml), sat'd NAHC03 (50 ml), and brine (50 ml), dried over magnesium sulfate, filtered, concentrated in vacuo by rotary evaporation, and chromatographed on silica gel (2% to 5% MeOH/CH2Cl2) to yield the title compound (116 mg, 66% for two steps); 1H NMR (CDCl3)]: δ 0.99 (d, J = 6.3 Hz, 3H), 1.01 (d, J = 6.3 Hz, 3H), 1.50-1.96 (m, 8H), 2.10-2.20 (m, 1H), 2.38-2. 53 (m, 2H), 3.19 (d, J = 14.2 Hz, 1H), 3.66-3.75 (m, 1H), 3.81-3.93 (m, 2H), 4.10 (d, J = 15.2 Hz, 1H), 4.58-4.65 (m, 1H), 6.66 (brs, 1H), 7.01 (d, J = 8.1 Hz, 1H), 7.31-7.56 (m, 4H), 7.70 (d, J = 7.6 Hz, 1H); LCMS: 442.2 (MH+).

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2003/103574, 2003, A2 Location in patent: Page 25; 21

41
[ 496-41-3 ]
[ 95-76-1 ]
[ 420097-22-9 ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: Benzofuran-2-carboxylic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran for 1h; Inert atmosphere; Stage #2: m,p-dichloroaniline In tetrahydrofuran at 20℃; for 14h; Inert atmosphere;	General procedure for the synthesis of benzofuran-2-carboxylic acid N-(substituted)phenylamide derivatives (3a-4k) General procedure: To a mixture of benzofuran-2-carboxylic acid (8) (1 eq) and 1,1’-carbodiimidazole (1.2 eq) in anhydrous THF was stirred for 1h then substituted aniline (0.9 eq) was added at room temperature. After stirring for 14 h, solvent was evaporated then the mixture acidified with 6N HCl to pH 2. The mixture was extracted with EtOAc (3 × 20 mL). The combined extracts were dried over anhydrous MgSO4 and the solvent was evaporated. After evaporation, the residue was purified by column chromatography (EtOAc/hexane = 1:2 - 1:50).
	Stage #1: Benzofuran-2-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 20℃; Stage #2: m,p-dichloroaniline In 1,4-dioxane at 50℃;

Reference： [1]Choi, Minho; Jo, Hyeju; Park, Hyun-Jung; Sateesh Kumar, Arepalli; Lee, Joonkwang; Yun, Jieun; Kim, Youngsoo; Han, Sang-Bae; Jung, Jae-Kyung; Cho, Jungsook; Lee, Kiho; Kwak, Jae-Hwan; Lee, Heesoon [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 12, p. 2545 - 2549]
[2]Engers, Darren W.; Niswender, Colleen M.; Weaver, C. David; Jadhav, Satyawan; Menon, Usha N.; Zamorano, Rocio; Conn, P. Jeffrey; Lindsley, Craig W.; Hopkins, Corey R. [Journal of Medicinal Chemistry, 2009, vol. 52, # 14, p. 4115 - 4118]

42
[ 496-41-3 ]
[ 3304-51-6 ]
[ 857646-43-6 ]

Yield	Reaction Conditions	Operation in experiment
		Example 243-1; (2S)-2- (l-Benzofuran-2-ylcarbonyl) amino-5- [ (benzyloxycarbonyl) amino] pentanoic acid; To a solution of (2S)-2-amino-5-[(benzyloxycarbonyl) amino] pentanoic acid (5. 0g, 18. 77mmol) in NMP (50mL),. was added BSA (11. 6mL, 46.93mmol), and the mixture was stirred for 1 hour at room temperature. To the reaction mixture was added a mixture of 1-benzofuran-2-carboxylic acid (3.35g, 20. 65mmol), PyBOP (10.74g, 20. 65mmol) and DIEA (7. 37mL, 41. 29mmol) in NMP (40mL). The mixture was stirred 24 hours at room temperature. The resultant mixture was partitioned between 25% n-hexane in EtOAc and 10% aqueous KHSO4solution. The organic phase was separated, washed with brine, and dried over MgSO4. Evaporation of the solvent gave a residue, which was purified by column chromatography on silica-gel (CHC13-MeOH 9: 1) to give the target compound (4.1g, 49. 9%) as a foam. MS ( (-) ESI) m/z : 409 (M-H)-. 1H-NMR (DMSO-d6) : 6 1.40-1. 95 (4H, m), 2.95-3. 10 (2H, m), 4.30-4. 45 (1H, m), 5.01 (2H, s), 7.25-7. 45 (7H, m), 7.44-7. 53 (1H, m), 7.63-7. 82 (3H, m), 8.85 (1H, d, J=7. 9Hz).

Reference： [1]Patent: WO2005/61475,2005,A2 .Location in patent: Page/Page column 164

43
[ 169447-86-3 ]
[ 496-41-3 ]
C₂₅H₂₈N₂O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 3771 - 3774

44
[ 54008-77-4 ]
[ 2258-42-6 ]
[ 496-41-3 ]

Reference： [1]Synthetic Communications,2012,vol. 42,p. 658 - 666

45
[ 496-41-3 ]
[ 112275-50-0 ]
[ 1397262-93-9 ]

Yield	Reaction Conditions	Operation in experiment
87%	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 20h; Inert atmosphere;	tert-Butyl 4-(benzofuran-2-carbonyl)-homopiperazine-1-carboxylate (41) To a suspension of EDC·HCl (2.99 g, 15.6 mmol, 1.2 equiv.) and NMM (5.72 mL, 52 mmol, 4 equiv.) in N,N-dimethylformamide (40 mL) were added successively HOBt (2.11 g, 15.6 mmol, 1.2 equiv.) and benzofuran-2-carboxylic acid 21 (2.11 g, 13 mmol, 1 equiv.). To this mixture was added a solution of N-tert-butoxycarbonylhomopiperazine 40 (2.60 g, 13 mmol, 1 equiv.) in N,N-dimethylformamide (12 mL). The reaction was allowed to stir at RT for 20 h and then diluted with water (200 mL) and extracted with ethyl acetate (3 × 200 mL). The combined organic fractions were then washed with brine, dried (Na2SO4) and concentrated under reduced pressure to give a viscous oil. Purification by column chromatography on silica gel (50:50 v/v hexanes:EtOAc) afforded the title compound 41 as a light yellow oil (3.89 g, 87%); Rf 0.33 (50:50 v/v hexanes:EtOAc); IR (ZnSe) 2974, 1685 (C=O), 1624, 1412, 1252, 1161, 926, 744, 467; 1H NMR (300 MHz, CDCl3) δ 7.65 (1H, d, J = 7.8 Hz, ArH), 7.51 (1H, d, J = 7.8 Hz, ArH), 7.34 (1H, dd, J = 7.8 Hz, J = 7.8 Hz, ArH), 7.30 (1H, br s, furan H), 7.23 (1H, dd, J = 7.8 Hz, J = 7.8 Hz, ArH), 3.93 (2H, app. br s, CH2), 3.84 (2H, app. br s, CH2), 3.63 (2H, app. br s, CH2), 3.47 (2H, app. br s, CH2), 2.04 (2H, app. br s, CH2CH2CH2), 1.47 (9H, s, 3 CH3); 13C NMR (75.5 MHz, CDCl3) δ 161.1 (C), 155.6 (C), 155.1 (C), 149.7 (C), 127.3 (C), 126.9 (aryl), 124.0 (aryl), 122.7 (aryl), 112.5 (aryl), 112.2 (furan CH), 80.3 (C(CH3)3), 50.3 (homopiperaz. CH2), 49.4 (homopiperaz. CH2), 48.6 (homopiperaz. CH2), 46.8 (homopiperaz. CH2), 28.8 (CH3), 26.5 (CH2CH2CH2); HRMS (+ESI) Calc. for C19H24N2O4 [M + Na]+ 367.1628, found: 367.1630; m/z (+ESI) 367.00 ([M + Na]+, 25%), 711.07 ([2M + Na]+, 100%).

Reference： [1]Moussa, Iman A.; Banister, Samuel D.; Manoli, Miral; Doddareddy, Munikumar Reddy; Cui, Jinquan; MacH, Robert H.; Kassiou, Michael [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 17, p. 5493 - 5497]

46
[ 496-41-3 ]
[ 100-46-9 ]
[ 21315-63-9 ]

Yield	Reaction Conditions	Operation in experiment
91%	With tris(1,2-dioxyphenyl)cyclotriphosphazene In toluene at 128℃; for 16h; Inert atmosphere; Dean-Stark;	Amides; General Procedure General procedure: An oven-dried 50 mL two-necked round-bottom flask was equippedwith a Teflon coated magnetic stirrer bar and connected to an azeotropiccondenser. To seal the apparatus, a balloon was connected tothe azeotropic condenser by a three-way stopcock; then, the atmospherewas replaced by N2 gas. Under a flow of N2, the flask wascharged with the CA (0.5 mmol, 1 equiv) and TAP-1 (11.48 mg, 5mol%). Then, the amine (0.5 mmol, 1 equiv) was added under N2 flow,followed by the solvent (dehydrated toluene or chlorobenzene; 7 mL).The reaction mixture was stirred under azeotropic reflux at 128 °C(133 °C in the case of chlorobenzene) for 16 h. Thereafter, the reaction flask was cooled to r.t., and the solvent was evaporated under reducedpressure using a rotary evaporator. The purification was performedby a three-step acid/base extraction. To this end, a separatory funnelwas charged with H2O and a DCM solution of the crude product mixture;after extraction, the organic layers (3 × 25 mL of DCM) were collectedand washed with sat. aq Na2CO3 (25 mL). The aqueous layerwas subsequently extracted with DCM (3 × 25 mL), and the organicphases were combined. The combined organic phases were washedwith aq HCl (1 M, 25 mL). The aqueous phase was extracted withDCM (3 × 25 mL). The combined organic layers were washed withbrine solution, dried over Na2SO4, and filtered. Finally the solvent ofthe filtrate was removed under reduced pressure.
88%	With tetrakis(dimethylamido)diborane In chlorobenzene for 7h; Reflux;
68%	With 1-Methylpyrrolidine; diphenylsilane In acetonitrile at 100℃; for 1h; Microwave irradiation; Green chemistry;

With Bromotrichloromethane; 4-(diphenylphosphino)-benzyltrimethylammonium bromide; triethylamine In tetrahydrofuran at 60℃; for 6h; Inert atmosphere;

4.3 Typical experimental procedure for amidation with IS-PPh₃ General procedure: IS-PPh3 (746 mg, 1.8 mmol) was dried by a vacuum pump for 2 h at 70 °C. To a flask containing IS-PPh3 were added 4-methoxycarboxylic acid (152 mg, 1.0 mmol), BrCCl3 (357 mg, 1.8 mmol), benzylamine (129 mg, 1.2 mmol), triethylamine (0.14 mL, 1.0 mmol), and THF (4 mL). The obtained mixture was stirred for 6 h at 60 °C under Ar atmosphere. After the reaction, diethyl ether (10 mL) and aq HCl (1 M, 2 mL) were added at 0 °C and the obtained mixture was stirred for 15-30 min at room temperature. Then, the reaction mixture was poured into water (8 mL) and the obtained mixture was extracted with diethyl ether (10 mL×4). The combined organic layer was washed with water (10 mL) and brine (10 mL), and then dried over Na2SO4. After removal of the solvent under reduced pressure, N-benzyl-4-methoxybenzamide was obtained in 93% yield with 99% purity, as estimated by 1H NMR measurement. For cinnamic and aliphatic amides (entries 18-25 in Table 2) and indole-2-carboxamide (entry 16 in Table 2), the reaction mixture was poured into water (8 mL) and the obtained mixture was extracted with chloroform (10 mL×4). The combined organic layer was washed with water (10 mL) and brine (10 mL), and then dried over Na2SO4. After removal of the solvent under reduced pressure, N-benzylamide was obtained. or the recovery of IS-Ph3PO, NaCl (5.0 g) was added to the aqueous layer. The aqueous solution was extracted with CHCl3 (10 mL×5) and the combined organic layer was dried over NaSO4. After removal of the solvent, IS-Ph3PO containing a trace amount of IS-Ph3P was obtained in 95% yield.

Reference： [1]Movahed, Farzaneh Soleymani; Sawant, Dinesh N.; Bagal, Dattatraya B.; Saito, Susumu [Synthesis, 2020, vol. 52, # 21, p. 3253 - 3262]
[2]Sawant, Dinesh N.; Bagal, Dattatraya B.; Ogawa, Saeko; Selvam, Kaliyamoorthy; Saito, Susumu [Organic Letters, 2018, vol. 20, # 15, p. 4397 - 4400]
[3]D'Amaral, Melissa C.; Jamkhou, Nick; Adler, Marc J. [Green Chemistry, 2021, vol. 23, # 1, p. 288 - 295]
[4]Kawagoe, Yuhsuke; Moriyama, Katsuhiko; Togo, Hideo [Tetrahedron, 2013, vol. 69, # 19, p. 3971 - 3977]

47
[ 496-41-3 ]
[ 41717-32-2 ]

Reference： [1]European Journal of Organic Chemistry,2013,p. 5886 - 5892
[2]Organic Letters,2019,vol. 21,p. 6779 - 6784

48
[ 496-41-3 ]
[ 75-03-6 ]
[ 3199-61-9 ]

Reference： [1]European Journal of Organic Chemistry,2013,p. 5886 - 5892

49
[ 578-66-5 ]
[ 496-41-3 ]
[ 876690-37-8 ]

Yield	Reaction Conditions	Operation in experiment
73%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 0 - 20℃; for 24.3333h;	Synthesis of substrates 1a-e from the carboxylic acids General procedure: To a solution of the benzofuran-2-carboxylic acid substrate (1.0 equiv) in DCM (0.1 M), wasadded 8-AQ (1.5 equiv), HATU (1.7 equiv.) and DIPEA (1.9 equiv). The resulting reactionmixture was stirred at 0 °C for 20 min and then at rt for 24 h. Then, the reaction mixture wasdiluted with DCM and washed with H2O (3x). The organic layer was dried over MgSO4,filtered and concentrated under reduced pressure. Pure products were obtained followingcolumn chromatography (0-2% MeOH in DCM)
	With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 15h; Inert atmosphere;
	Stage #1: Benzofuran-2-carboxylic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 0.166667h; Stage #2: 8-amino quinoline In N,N-dimethyl-formamide for 20h;	N-(Quinolin-8-yl)benzofuran-2-carboxamide H7 [00451] Benzofuran-2-carboxylic acid (1.0 mmol) and N-(3-dimethylaminopropyl)-N’- ethylcarbodiimide hydrochloride (1.2 mmol) were dissolved in dimethylformamide (5 mL). N,N-Diisopropylethylamine (1.5 mmol) was added and the solution was stirred for 10 mm. To this solution 8-aminoquinoline (1.0 mmol) was added, and the mixture was stirred for 20 hrs. The mixture was diluted with water and extracted with 2 volumes of ethyl acetate. The organic layers were collected and the solvent was removed by rotary evaporation. The residue was purified by preparative reverse-phase HPLC using a water-acetonitrile gradient to afford the desired product H7. ESI-MS: m/z 289 [M+H]b.

Stage #1: Benzofuran-2-carboxylic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 0.166667h; Stage #2: 8-amino quinoline In N,N-dimethyl-formamide for 20h;

7.2.73 7.2.73. N-(Quinolin-8-yl)benzofuran-2-carboxamide H7 Benzofuran-2-carboxylic acid (1.0 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (1.2 mmol) were dissolved in dimethylformamide (5 mL). N,N-Diisopropylethylamine (1.5 mmol) was added and the solution was stirred for 10 min. To this solution 8-aminoquinoline (1.0 mmol) was added, and the mixture was stirred for 20 hrs. The mixture was diluted with water and extracted with 2 volumes of ethyl acetate. The organic layers were collected and the solvent was removed by rotary evaporation. The residue was purified by preparative reverse-phase HPLC using a water-acetonitrile gradient to afford the desired product H7. ESI-MS: m/z 289 [M+H]+.

Reference： [1]Holm, Linus Johansson; Oschmann, Michael; Pourghasemi‐Lati, Monireh; Verho, Oscar [Molecules, 2020, vol. 25, # 2]
[2]Kanyiva, Kyalo Stephen; Kuninobu, Yoichiro; Kanai, Motomu [Organic Letters, 2014, vol. 16, # 7, p. 1968 - 1971]
[3]Current Patent Assignee: NEURODON - WO2016/32569, 2016, A1 Location in patent: Page/Page column 214
[4]Current Patent Assignee: NEURODON - US2019/151303, 2019, A1 Location in patent: Paragraph 0714

50
[ 496-41-3 ]
[ 1605323-33-8 ]
[ 1605323-78-1 ]

Yield	Reaction Conditions	Operation in experiment
66.3%	Stage #1: Benzofuran-2-carboxylic acid; (2S,3R)-2-amino-3-hydroxy-N-octylbutanamide With benzotriazol-1-ol In tetrahydrofuran at 0℃; for 0.0833333h; Stage #2: With 4-methyl-morpholine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 0 - 20℃;	12 Example 12: Condensation of NZJU1-NZJU4 with Benzofuran-2-carboxylic Acid General procedure: At 0°C, to a solution of 1.0 mmol of benzofuran-2-carboxylic acid in anhydrous THF(20mL),0.135g(1.0mmol) of HOBt and 1.0 mmol of (2S,3R)- 2-Amino-3-hydroxy-N-octylbutanamide, (2S,3R)-2-Amino-3-hydroxy-N- dodecylbutanamide, (2 S,3 R)-2-Amino-3 -hydroxy-N-tetradecylbutanamide, or (2S,3R)-2-Amino-3-hydroxy-N-octadecylbutanamide were added. After 5 min, 0.220g (1.1 mmol) of EDC-HCl was added, and the pH of the solution was adjusted to 8-9 with 4-methylmorpholine. The mixture was stirred at 0 °C for 2 h and at room temperature overnight. On evaporation the residue was dissolved in 80 mL of ethyl acetate. The solution was washed successively with saturated sodium bicarbonate, 5% potassium bisulfate, and saturated sodium chloride, and the organic phase was separated and dried over anhydrous magnesium sulfate for 2 h. After filtration and evaporation under reduced pressure crude product was obtained and recrystallized using ethyl acetate to obtain compounds NZJUlh, NZJU2h, NZJU3h, and NZJU4h. N-((2S,3R)-3-hydroxy- 1-oxo- l-(octylamino)butan-2-yl)-benzofuran- 2-carboxamide (NZJUlh) was obtained in a yield of 0.248 g (66.3%) as colorless powder. XH NMR (300 MHz, CDC13) δ 7.70 (d, J= 6.9 Hz, 1H), 7.66 (d, J= 7.8 Hz, 1H), 7.53 (d, J= 8.3 Hz, 1H), 7.48 (s, 1H), 7.46 - 7.37 (m, 1H), 7.33 - 7.27 (m, 1H), 6.96 (s, 1H), 4.61 - 4.42 (m, 2H), 3.36 - 3.12 (m, 2H), 1.57 - 1.41 (m, 2H), 1.37 - 1.06 (m, 13H), 0.83 (t, J= 6.7 Hz, 3H); 13C NMR (75 MHz, CDC13) δ 170.3, 159.8, 155.0, 147.9, 127.3, 123.8, 122.7, 112.0, 11 1.2, 66.8, 57.2, 39.7, 31.8, 29.4, 29.2, 26.9, 22.6, 18.2, 14.1; ESI/MS (m/e) 409.15 [M+Cl]"; Anal. Calcd. For C21H30 2O4: C, 67.35; H, 8.07; N, 7.48%. Found: C, 67.37; H, 8.13; N, 7.39%. N-((2S,3R)-3-hydroxy- 1-oxo- 1 -(dodecylamino)butan-2-yl)- benzofuran- 2-carboxamide (NZJU2h) was obtained in a yield of 0.276 g (64.2%) as colorless powder. XH NMR (300 MHz, CDC13) δ 7.76 - 7.61 (m, 2H), 7.53 (d, J= 8.3 Hz, 1H), 7.48 (s, 1H), 7.47 - 7.38 (m, 1H), 7.31 (d, J = 7.2 Hz, 1H), 6.95 (s, 1H), 4.64 - 4.41 (m, 2H), 3.39 - 3.09 (m, 2H), 1.59 - 1.41 (m, 2H), 1.39 - 1.02 (m, 21H), 0.87 (t, J= 6.6 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 170.6, 159.8, 155.0, 147.8, 127.4, 123.9, 122.7, 112.1, 111.3, 66.6, 56.8, 39.7, 31.9, 29.6, 29.6, 29.5, 29.4, 29.3, 26.9, 22.7,18.2, 14.1; ESI/MS (m/e) 431.10 [M+H]+; Anal. Calcd. For C25H38N2O4: C, 69.74; H, 8.90; N, 6.51%. Found: C, 69.78; H, 8.76; N, 6.44%. N-((2S,3R)-3-hydroxy- 1-oxo- 1 -(tetradecylamino)butan-2-yl)- benzofuran- 2-carboxamide (NZJU3h) was obtained in a yield of 0.323 g (70.5%) as colorless powder. XH NMR (300 MHz, CDC13) δ 7.74 - 7.60 (m, 2H), 7.54 (d, J= 8.3 Hz, 1H), 7.50 (s, 1H), 7.44 (t, J= 7.6 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H), 6.85 (s, 1H), 4.61 - 4.44 (m, 2H), 3.37 - 3.09 (m, 2H), 1.58 - I.40 (m, 2H), 1.41 - 1.01 (m, 25H), 0.88 (t, J= 6.5 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 170.5, 159.7, 155.0, 147.8, 127.3, 123.8, 122.7, 112.1, 111.2, 66.6, 56.9, 39.7, 31.9, 29.7, 29.5, 29.4, 29.3, 26.9, 22.7, 18.2, 14.1; ESI/MS (m/e) 459.15 [M+H]+; Anal. Calcd. For C27H42N2O4: C, 70.71; H, 9.23; N, 6.11%. Found: C, 70.59; H, 9.29; N, 6.18%. N-((2S,3R)-3-hydroxy- 1-oxo- 1 -(octadecylamino)butan-2-yl)- benzofuran- 2-carboxamide (NZJU4h) was obtained in a yield of 0.362 g (70.4%) as colorless powder. XH NMR (300 MHz, CDC13) δ 7.71 - 7.62 (m, 2H), 7.54 (d, J= 8.3 Hz, 1H), 7.50 (s, 1H), 7.48 - 7.40 (m, 1H), 7.30 (t, J= 7.2 Hz, 1H), 6.87 (s, 1H), 4.59 - 4.44 (m, 2H), 3.35 - 3.15 (m, 2H), 1.57 - 1.43 (m, 2H), 1.36 - 1.11 (m, 33H), 0.88 (t, J= 6.6 Hz, 3H); 13C NMR (75 MHz, CDCI3) δ 170.4, 159.7, 155.0, 147.8, 127.3, 123.8, 122.7, 112.0, 111.2, 66.6, 56.9, 39.7, 31.9, 29.7, 29.6, 29.5, 29.4, 29.3, 26.9, 22.7, 18.2, 14.1; ESI/MS (m/e) 515.25 [M+H]+; Anal. Calcd. For C31H50N2O4: C, 72.33; H, 9.79; N, 5.44%. Found: C, 72.31; H, 9.81; N, 5.43%.
66.3%	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 0 - 20℃;	2.1.2. Synthetic procedure for 5xa-xj General procedure: To a solution of carboxylic acid (1.0 mmol) in anhydrous THF (20 mL) were added (2S,3R)-2-amino-3-hydroxy-N-alkylbutanamide 4a-d (1.0 mmol) and HOBt (1.0 mmol, 0.135 g) at 0 °C. After the reaction mixture was stirred for 5 min, EDC·HCl (0.220 g, 1.1 mmol) was added. The pH value of the solution was adjusted to 8-9 with 4-methylmorpholine. The reaction mixture was stirred at 0 °C for 2 h and overnight at room temperature. After evaporation of the mixture in vacuo, the residue was dissolved in ethyl acetate (50 mL). The solution was washed successively with saturated NaHCO3, 5% KHSO4, and saturated NaCl. The organic phase was separated and dried over anhydrous MgSO4. After filtration and evaporation in vacuo, residue was purified by recrystallization in petroleum ester/ethyl acetate to give the desired ceramide analogues 5xa-xj.

Reference： [1]Current Patent Assignee: UNIVERSITY SYSTEM OF GEORGIA; ZHEJIANG UNIVERSITY - WO2014/66613, 2014, A2 Location in patent: Page/Page column 92-93
[2]Liu, Qianqian; Li, Xia; Bao, Yong-Sheng; Lu, Jingxin; Li, Hua; Huang, Zhizhen; Liu, Feiyan [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 8, p. 1489 - 1496]

51
[ 496-41-3 ]
[ 18107-18-1 ]
[ 1646-27-1 ]

Reference： [1]Chemical Communications,2014,vol. 50,p. 14360 - 14363
[2]Green Chemistry,2018,vol. 20,p. 3931 - 3943

52
[ 6142-06-9 ]
[ 496-41-3 ]
N-methyl-N-(thiazol-2-yl)benzofuran-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With N-ethyl-N,N-diisopropylamine; HATU; In ethyl acetate; N,N-dimethyl-formamide; at 0 - 20℃; for 24.5h;Inert atmosphere;	Example 2 N-methyl-N-(thiazol-2-yl)benzofuran-2-carboxamide [0287] benzofuran-2-carboxylic acid (30 mg, 0.17 mmol) and <strong>[6142-06-9]N-methyl-2-thiazolamine</strong> (24.3 mg, 0.213 mmol) in DMF (1 mL) at 0 C. was added HATU (80.8 mg, 0.213 mmol), followed by addition of DIEA (63.8 mul, 0.366 mmol). After stirring under argon at 0 C. for 0.5 hours and at room temperature over 24 hours, the reaction mixture was taken up in EtOAc (10 mL) and 0.1 N HCl (10 mL). The organic layers were washed with 0.1 N NaOH (10 mL), brine (5 mL), dried (Na2SO4) and concentrated in vacuo. The resulting solid was chromatographed on silica gel with 5% and 10% EtOAc/hexane to give the target molecule as a white solid (38 mg, 82%).

Reference： [1]Patent: US2015/126507,2015,A1 .Location in patent: Paragraph 0287-0288

53
[ 496-41-3 ]
[ 62-53-3 ]
[ 50635-12-6 ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: Benzofuran-2-carboxylic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran for 1h; Inert atmosphere; Stage #2: aniline In tetrahydrofuran at 20℃; for 14h; Inert atmosphere;	General procedure for the synthesis of benzofuran-2-carboxylic acid N-(substituted)phenylamide derivatives (3a-4k) General procedure: To a mixture of benzofuran-2-carboxylic acid (8) (1 eq) and 1,1’-carbodiimidazole (1.2 eq) in anhydrous THF was stirred for 1h then substituted aniline (0.9 eq) was added at room temperature. After stirring for 14 h, solvent was evaporated then the mixture acidified with 6N HCl to pH 2. The mixture was extracted with EtOAc (3 × 20 mL). The combined extracts were dried over anhydrous MgSO4 and the solvent was evaporated. After evaporation, the residue was purified by column chromatography (EtOAc/hexane = 1:2 - 1:50).
77%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 0 - 20℃; for 24.3333h;	Synthesis of substrates 1a-e from the carboxylic acids General procedure: To a solution of the benzofuran-2-carboxylic acid substrate (1.0 equiv) in DCM (0.1 M), wasadded 8-AQ (1.5 equiv), HATU (1.7 equiv.) and DIPEA (1.9 equiv). The resulting reactionmixture was stirred at 0 °C for 20 min and then at rt for 24 h. Then, the reaction mixture wasdiluted with DCM and washed with H2O (3x). The organic layer was dried over MgSO4,filtered and concentrated under reduced pressure. Pure products were obtained followingcolumn chromatography (0-2% MeOH in DCM)

Reference： [1]Choi, Minho; Jo, Hyeju; Park, Hyun-Jung; Sateesh Kumar, Arepalli; Lee, Joonkwang; Yun, Jieun; Kim, Youngsoo; Han, Sang-Bae; Jung, Jae-Kyung; Cho, Jungsook; Lee, Kiho; Kwak, Jae-Hwan; Lee, Heesoon [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 12, p. 2545 - 2549]
[2]Holm, Linus Johansson; Oschmann, Michael; Pourghasemi‐Lati, Monireh; Verho, Oscar [Molecules, 2020, vol. 25, # 2]

54
[ 496-41-3 ]
[ 95-53-4 ]
benzofuran-2-carboxylic acid N-(2-methylphenyl)amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	Stage #1: Benzofuran-2-carboxylic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran for 1h; Inert atmosphere; Stage #2: <i>o</i>-toluidine In tetrahydrofuran at 20℃; for 14h; Inert atmosphere;	General procedure for the synthesis of benzofuran-2-carboxylic acid N-(substituted)phenylamide derivatives (3a-4k) General procedure: To a mixture of benzofuran-2-carboxylic acid (8) (1 eq) and 1,1’-carbodiimidazole (1.2 eq) in anhydrous THF was stirred for 1h then substituted aniline (0.9 eq) was added at room temperature. After stirring for 14 h, solvent was evaporated then the mixture acidified with 6N HCl to pH 2. The mixture was extracted with EtOAc (3 × 20 mL). The combined extracts were dried over anhydrous MgSO4 and the solvent was evaporated. After evaporation, the residue was purified by column chromatography (EtOAc/hexane = 1:2 - 1:50).

Reference： [1]Choi, Minho; Jo, Hyeju; Park, Hyun-Jung; Sateesh Kumar, Arepalli; Lee, Joonkwang; Yun, Jieun; Kim, Youngsoo; Han, Sang-Bae; Jung, Jae-Kyung; Cho, Jungsook; Lee, Kiho; Kwak, Jae-Hwan; Lee, Heesoon [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 12, p. 2545 - 2549]

55
[ 496-41-3 ]
[ 95-64-7 ]
benzofuran-2-carboxylic acid N-(3,4-dimethylphenyl)amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: Benzofuran-2-carboxylic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran for 1h; Inert atmosphere; Stage #2: 4-amino-o-xylene In tetrahydrofuran at 20℃; for 14h; Inert atmosphere;	General procedure for the synthesis of benzofuran-2-carboxylic acid N-(substituted)phenylamide derivatives (3a-4k) General procedure: To a mixture of benzofuran-2-carboxylic acid (8) (1 eq) and 1,1’-carbodiimidazole (1.2 eq) in anhydrous THF was stirred for 1h then substituted aniline (0.9 eq) was added at room temperature. After stirring for 14 h, solvent was evaporated then the mixture acidified with 6N HCl to pH 2. The mixture was extracted with EtOAc (3 × 20 mL). The combined extracts were dried over anhydrous MgSO4 and the solvent was evaporated. After evaporation, the residue was purified by column chromatography (EtOAc/hexane = 1:2 - 1:50).

Reference： [1]Choi, Minho; Jo, Hyeju; Park, Hyun-Jung; Sateesh Kumar, Arepalli; Lee, Joonkwang; Yun, Jieun; Kim, Youngsoo; Han, Sang-Bae; Jung, Jae-Kyung; Cho, Jungsook; Lee, Kiho; Kwak, Jae-Hwan; Lee, Heesoon [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 12, p. 2545 - 2549]

56
[ 496-41-3 ]
[ 328-93-8 ]
benzofuran-2-carboxylic acid N-(2,5-ditrifluoromethylphenyl)amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
7%		General procedure: To a mixture of benzofuran-2-carboxylic acid (8) (1 eq) and 1,1?-carbodiimidazole (1.2 eq) in anhydrous THF was stirred for 1h then substituted aniline (0.9 eq) was added at room temperature. After stirring for 14 h, solvent was evaporated then the mixture acidified with 6N HCl to pH 2. The mixture was extracted with EtOAc (3 × 20 mL). The combined extracts were dried over anhydrous MgSO4 and the solvent was evaporated. After evaporation, the residue was purified by column chromatography (EtOAc/hexane = 1:2 ? 1:50).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 2545 - 2549

57
[ 496-41-3 ]
[ 32837-87-9 ]
2-(1-benzofuran-2-yl)-5,5-dimethyl-4-oxo-4,5-dihydro-3-furancarbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With triethylamine In acetonitrile at 100℃; for 3h; Microwave irradiation; chemoselective reaction;	Synthesis of 3(2H)-Furanones 3a-f General procedure: 2-(2-Furyl)-5,5-dimethyl-4-oxo-4,5-dihydro-3-furancarbonitrile (3a). To a stirred solutionoffuran-2-carboxylic acid (1a) (112 mg,1 mmol) and 4-hydroxy-4-methyl-2-pentynenitrile (2a) (135 mg,1.2 mmol) in MeCN (5 mL), Et3N (101 mg,1 mmol) was added dropwise over 1 min. The reaction mixture was irradiated with microwave at 100 °C at 1.2 atm for 2 h (or was stirred at 100 °C for 5 h). The residue was concentrated and washed with a mixture of C5H12-(CH3)2CO, 5:1 and 3:1, and then recrystallized with (CH3)2CO to give the desired product 3a as colorless crystals (172 mg, 85% or163 mg, 80% at 100°C);

Reference： [1]Trofimov, Boris A.; Stepanov, Anton V.; Malkina, Anastasiya G.; Volostnykh, Olga G.; Shemyakina, Olesya A.; Ushakov, Igor A. [Synthetic Communications, 2015, vol. 45, # 23, p. 2718 - 2729]

58
[ 496-41-3 ]
[ 32837-88-0 ]
2-(1-benzofuran-2-yl)-5-ethyl-5-methyl-4-oxo-4,5-dihydro-3-furancarbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylamine In acetonitrile at 100℃; for 17h; Microwave irradiation; chemoselective reaction;	Synthesis of 3(2H)-Furanones 3a-f General procedure: 2-(2-Furyl)-5,5-dimethyl-4-oxo-4,5-dihydro-3-furancarbonitrile (3a). To a stirred solutionoffuran-2-carboxylic acid (1a) (112 mg,1 mmol) and 4-hydroxy-4-methyl-2-pentynenitrile (2a) (135 mg,1.2 mmol) in MeCN (5 mL), Et3N (101 mg,1 mmol) was added dropwise over 1 min. The reaction mixture was irradiated with microwave at 100 °C at 1.2 atm for 2 h (or was stirred at 100 °C for 5 h). The residue was concentrated and washed with a mixture of C5H12-(CH3)2CO, 5:1 and 3:1, and then recrystallized with (CH3)2CO to give the desired product 3a as colorless crystals (172 mg, 85% or163 mg, 80% at 100°C);

Reference： [1]Trofimov, Boris A.; Stepanov, Anton V.; Malkina, Anastasiya G.; Volostnykh, Olga G.; Shemyakina, Olesya A.; Ushakov, Igor A. [Synthetic Communications, 2015, vol. 45, # 23, p. 2718 - 2729]

59
[ 496-41-3 ]
[ 32837-89-1 ]
2-(1-benzofuran-2-yl)-4-oxo-1-oxaspiro[4.5]dec-2-ene-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With triethylamine In acetonitrile at 100℃; for 12h; Microwave irradiation; chemoselective reaction;	Synthesis of 3(2H)-Furanones 3a-f General procedure: 2-(2-Furyl)-5,5-dimethyl-4-oxo-4,5-dihydro-3-furancarbonitrile (3a). To a stirred solutionoffuran-2-carboxylic acid (1a) (112 mg,1 mmol) and 4-hydroxy-4-methyl-2-pentynenitrile (2a) (135 mg,1.2 mmol) in MeCN (5 mL), Et3N (101 mg,1 mmol) was added dropwise over 1 min. The reaction mixture was irradiated with microwave at 100 °C at 1.2 atm for 2 h (or was stirred at 100 °C for 5 h). The residue was concentrated and washed with a mixture of C5H12-(CH3)2CO, 5:1 and 3:1, and then recrystallized with (CH3)2CO to give the desired product 3a as colorless crystals (172 mg, 85% or163 mg, 80% at 100°C);

Reference： [1]Trofimov, Boris A.; Stepanov, Anton V.; Malkina, Anastasiya G.; Volostnykh, Olga G.; Shemyakina, Olesya A.; Ushakov, Igor A. [Synthetic Communications, 2015, vol. 45, # 23, p. 2718 - 2729]

60
[ 496-41-3 ]
[ 89756-60-5 ]
C₁₁H₁₂N₂O₄S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 2054 - 2066

61
[ 496-41-3 ]
[ 6638-79-5 ]
N-methoxy-N-methylbenzofuran-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: Benzofuran-2-carboxylic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1h; Stage #2: N,O-dimethylhydroxylamine*hydrochloride With pyridine In dichloromethane at 0 - 20℃; for 18h;	N-Methoxy-N-methylbenzofuran-2- rboxamide (121) Oxalyl chloride (3.13 mL, 3.70 mmol) was added to a suspension of benzofuran-2- carboxylic acid (5.00 g, 3.08 mmol) in DCM (100 mL, anhydrous) and DMF (0.1 mL, 1.3 mmol) at r.t.. The mixture was stirred at r.t. for 1 h to give a colourless solution which was cooled to 0 °C. N,O-Dimethylhydroxylamine hydrochloride (3.31 g, 3.39 mmol) and pyridine (7.5 mL, 9.27 mmol) were added sequentially and the mixture was stirred at r.t. for 18 h, then partitioned between EtOAc and sat. aq. NaHC03. Column chromatography (3 : 1 hexanes:EtOAc) gave 121 (6.32 g, 100%). 1H MR (CDC13) δ 7.69 (ddd, 7.9, 1.2, 0.7 Hz, 1H), 7.61 (ddd, J = 8.4, 1.7, 0.9 Hz, 1H), 7.51 (d, J = 1.0 Hz, 1H), 7.48 (ddd, J = 7.9, 7.2, 1.3 Hz, 1H), 7.30 (ddd, J = 7.5, 7.3, 0.9 Hz, 1H), 3.84 (s, 3H), 3.43 (s, 3H). Found: [M+H]=206.2. l-(Benzofuran-2-yl)-3-(dimethylamino ropan-l-one (122)
100%	Stage #1: Benzofuran-2-carboxylic acid With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: N,O-dimethylhydroxylamine*hydrochloride With pyridine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 18h;	4.1.2.2. 1-(Benzofuran-2-yl)-3-(dimethylamino)propan-1-one (classD-2). Oxalyl chloride (3.13 mL, 3.70 mmol) was added to a suspensionof benzofuran-2-carboxylic acid (5.00 g, 3.08 mmol) in DCM(100 mL, anhydrous) and DMF (0.1 mL, 1.3 mmol) at 20 C. Themixture was stirred at 20 C for 1 h to give a colourless solutionwhich was cooled to 0 C. N,O-Dimethylhydroxylamine hydrochloride(3.31 g, 3.39 mmol) and pyridine (7.5 mL, 9.27 mmol) wereadded sequentially and the mixture was stirred at 20 C for 18 h,then partitioned between EtOAc and sat. aq. NaHCO3. Column chromatography(3:1 hexanes:EtOAc) gave N-methoxy-N-methylbenzofuran-2-carboxamide (6.32 g, 100%). 1H NMR (CDCl3) d 7.69(ddd, 7.9, 1.2, 0.7 Hz, 1H), 7.61 (ddd, J = 8.4, 1.7, 0.9 Hz, 1H),7.51 (d, J = 1.0 Hz, 1H), 7.48 (ddd, J = 7.9, 7.2, 1.3 Hz, 1H), 7.30(ddd, J = 7.5, 7.3, 0.9 Hz, 1H), 3.84 (s, 3H), 3.43 (s, 3H). Found:[M+H] = 206.2.
60%	With dmap; triethylamine; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;

Reference： [1]Current Patent Assignee: TB ALLIANCE INC; JOHNSON & JOHNSON INC - WO2017/155909, 2017, A1 Location in patent: Paragraph 0179
[2]Sutherland, Hamish S.; Tong, Amy S.T.; Choi, Peter J.; Conole, Daniel; Blaser, Adrian; Franzblau, Scott G.; Cooper, Christopher B.; Upton, Anna M.; Lotlikar, Manisha U.; Denny, William A.; Palmer, Brian D. [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 8, p. 1797 - 1809]
[3]Hu, Naifu; Jung, Hoimin; Zheng, Yu; Lee, Juhyeong; Zhang, Lilu; Ullah, Zakir; Xie, Xiulan; Harms, Klaus; Baik, Mu-Hyun; Meggers, Eric [Angewandte Chemie - International Edition, 2018, vol. 57, # 21, p. 6242 - 6246][Angew. Chem., 2018, vol. 130, p. 6350 - 6354,5]

62
[ 496-41-3 ]
[ 54008-77-4 ]
[ 64150-61-4 ]

Reference： [1]Chemical Science,2018,vol. 9,p. 3860 - 3865

63
[ 496-41-3 ]
[ 50919-77-2 ]
2-(benzofuran-2-carbonyl)-5-methyl-1H-indene-1,3(2H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;	2 3.2. General experimental procedure General procedure: In a 20 or 40 mL reaction vial equipped with magnetic stir bar and Teflon-lined cap, a solution of the corresponding carboxylic acid (1.5 mmol, 3.0 eq) and DMAP (183.3 mg, 1.5 mmol, 3.0 eq) in anhydrous DMF (9.0 mL) was homogenized by stirring for 5-10min. EDCI·HCl (287.6mg, 1.5mmol, 3.0 eq) was added, and the resulting mixture was homogenized by stirring for 5-10 min. The corresponding 1,3-indandione (0.5mmol, 1.0 eq) was added, and the resulting mixture was resealed and stirred for 12-72h, monitoring by LCMS. When complete, workup method A, B, or C was used to isolate the final products.

Reference： [1]Larsen, Brian J.; Rosano, Robert J.; Ford-Hutchinson, Thomas A.; Reitz, Allen B.; Wrobel, Jay E. [Tetrahedron, 2018, vol. 74, # 22, p. 2762 - 2768]

64
[ 496-41-3 ]
[ 27611-39-8 ]
2-(benzofuran-2-carbonyl)-5-bromo-1H-indene-1,3(2H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;	2 3.2. General experimental procedure General procedure: In a 20 or 40 mL reaction vial equipped with magnetic stir bar and Teflon-lined cap, a solution of the corresponding carboxylic acid (1.5 mmol, 3.0 eq) and DMAP (183.3 mg, 1.5 mmol, 3.0 eq) in anhydrous DMF (9.0 mL) was homogenized by stirring for 5-10min. EDCI·HCl (287.6mg, 1.5mmol, 3.0 eq) was added, and the resulting mixture was homogenized by stirring for 5-10 min. The corresponding 1,3-indandione (0.5mmol, 1.0 eq) was added, and the resulting mixture was resealed and stirred for 12-72h, monitoring by LCMS. When complete, workup method A, B, or C was used to isolate the final products.

Reference： [1]Larsen, Brian J.; Rosano, Robert J.; Ford-Hutchinson, Thomas A.; Reitz, Allen B.; Wrobel, Jay E. [Tetrahedron, 2018, vol. 74, # 22, p. 2762 - 2768]

65
[ 496-41-3 ]
[ 4535-07-3 ]
2-(benzofuran-2-carbonyl)-4-nitro-1H-indene-1,3(2H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;	2 3.2. General experimental procedure General procedure: In a 20 or 40 mL reaction vial equipped with magnetic stir bar and Teflon-lined cap, a solution of the corresponding carboxylic acid (1.5 mmol, 3.0 eq) and DMAP (183.3 mg, 1.5 mmol, 3.0 eq) in anhydrous DMF (9.0 mL) was homogenized by stirring for 5-10min. EDCI·HCl (287.6mg, 1.5mmol, 3.0 eq) was added, and the resulting mixture was homogenized by stirring for 5-10 min. The corresponding 1,3-indandione (0.5mmol, 1.0 eq) was added, and the resulting mixture was resealed and stirred for 12-72h, monitoring by LCMS. When complete, workup method A, B, or C was used to isolate the final products.

Reference： [1]Larsen, Brian J.; Rosano, Robert J.; Ford-Hutchinson, Thomas A.; Reitz, Allen B.; Wrobel, Jay E. [Tetrahedron, 2018, vol. 74, # 22, p. 2762 - 2768]

66
[ 606-23-5 ]
[ 496-41-3 ]
2-(benzofuran-2-carbonyl)-1H-indene-1,3(2H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;	2 3.2. General experimental procedure General procedure: In a 20 or 40 mL reaction vial equipped with magnetic stir bar and Teflon-lined cap, a solution of the corresponding carboxylic acid (1.5 mmol, 3.0 eq) and DMAP (183.3 mg, 1.5 mmol, 3.0 eq) in anhydrous DMF (9.0 mL) was homogenized by stirring for 5-10min. EDCI·HCl (287.6mg, 1.5mmol, 3.0 eq) was added, and the resulting mixture was homogenized by stirring for 5-10 min. The corresponding 1,3-indandione (0.5mmol, 1.0 eq) was added, and the resulting mixture was resealed and stirred for 12-72h, monitoring by LCMS. When complete, workup method A, B, or C was used to isolate the final products.

Reference： [1]Larsen, Brian J.; Rosano, Robert J.; Ford-Hutchinson, Thomas A.; Reitz, Allen B.; Wrobel, Jay E. [Tetrahedron, 2018, vol. 74, # 22, p. 2762 - 2768]

67
[ 496-41-3 ]
[ 154258-82-9 ]
C₂₆H₁₉FN₂O₂ [ No CAS ]
C₂₆H₁₉FN₂O₂ [ No CAS ]
C₂₆H₁₉FN₂O₂ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 6242 - 6246
Angew. Chem.,2018,vol. 130,p. 6350 - 6354,5

68
[ 496-41-3 ]
[ 154258-82-9 ]
C₁₈H₁₁FN₂O₂ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 6242 - 6246
Angew. Chem.,2018,vol. 130,p. 6350 - 6354,5

69
[ 496-41-3 ]
[ 27069-17-6 ]
C₂₇H₂₂N₂O₃ [ No CAS ]
C₂₇H₂₂N₂O₃ [ No CAS ]
C₂₇H₂₂N₂O₃ [ No CAS ]
C₂₇H₂₂N₂O₃ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 6242 - 6246
Angew. Chem.,2018,vol. 130,p. 6350 - 6354,5

70
[ 496-41-3 ]
[ 27069-17-6 ]
C₁₉H₁₄N₂O₃ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 6242 - 6246
Angew. Chem.,2018,vol. 130,p. 6350 - 6354,5

71
[ 1646-27-1 ]
[ 496-41-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In methanol; at 20℃;	General procedure: To a solution of intermediate 2a-c (1 equiv.) in methanol was added 2N sodium hydroxide at ambient temperature. The reaction mixture was stirred for 4 h and the methanol was removed by rotary evaporation. The resultant mixture was adjusted to pH =5-6 with 1N HCl. The precipitated white solid was collected by filtration and dried to give the carboxylic acid intermediate (1a-c).
	With sodium hydroxide; In methanol; at 60℃; for 7h;	The benzofuran -2 - carboxylic acid methyl ester 2 g (10.4 mmol) dissolved in 20 ml in methanol, adding 2 N NaOH solution (10 ml). Then the reaction mixture is 60 C under stirring 7 h, the completion of the thin layer chromatographic detection reaction, reduced pressure to remove the methanol, for 2 N hydrochloric acid to adjust the pH to 2 - 3, the filtering white solid, drying to obtain the desired compound.

Reference： [1]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 3242 - 3253
[2]ChemMedChem,2018,vol. 13,p. 1517 - 1529
[3]Patent: CN109232396,2019,A .Location in patent: Paragraph 0076; 0079; 0080

72
[ 90-02-8 ]
[ 105-39-5 ]
[ 496-41-3 ]
[ 3199-61-9 ]

Reference： [1]Chemical Biology and Drug Design,2018,vol. 92,p. 1497 - 1503

73
[ 4265-25-2 ]
[ 496-41-3 ]

Yield	Reaction Conditions	Operation in experiment
21.7%	With tetrakis(o-chlorophenyl)iron porphyrin; oxygen; potassium hydroxide; In ethanol; at 130℃; under 15001.5 Torr; for 2h;Autoclave;	1.41 g of potassium hydroxide was sequentially added to a 200 mL autoclave.2.82g <strong>[4265-25-2]2-methylbenzofuran</strong>, 30mL absolute ethanol,18 mg of metalloporphyrin tetrakis (o-chlorophenyl)iron porphyrin,Passing 2.0MPa of oxygen,The reaction was carried out at 130 C for 2 hours.The product is acidified, filtered,After recrystallization from hot water, benzofuran-2-carboxylic acid is obtained.The yield was 21.7%.

Reference： [1]Patent: CN109206388,2019,A .Location in patent: Paragraph 0019-0048

74
[ 496-41-3 ]
[ 495-78-3 ]

Reference： [1]Science,2019,vol. 363,p. 838 - 845

75
[ 496-41-3 ]
[ 66-71-7 ]
[ 7732-18-5 ]
nickel(II) nitrate [ No CAS ]
C₂₄H₂₀N₄NiO₂⁽²⁺⁾*2C₉H₅O₃^(1-)*5H₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: Benzofuran-2-carboxylic acid With sodium hydrogencarbonate In ethanol; water Stage #2: 1,10-Phenanthroline In ethanol; water for 1h; Stage #3: water; nickel(II) nitrate In ethanol at 60℃; for 5h;	General procedure: Firstly, coumarilate salt compounds with natrium cationwere synthesized by 0.005 mol of coumarilic acid dissolvedin a 50:50 (v/v) EtOH/H2O solution in a beakerfollowed by the addition of 0.005 mol of NaHCO3 providingCO2 output. Then, the 1,10-phenanthroline solution(0.005 mol 25 mL H2O) was first added to the salt solutionsand mixed for 1 h in the magnetic stirrer. Finally, themetal-nitrate salts (0.0025 mol) in solid phase wereappended to the main solution in 1:2 ratio concerning thecoumarilate anion and mixed for 5 h at 60 C (Scheme 2,Eq. 2).The final solution was allowed to crystallize at atmosphericpressure by standing at room temperature. Thecrystals precipitated in approximately 20-30 days werecollected by filtration. The metal/ligand/ligand ratio wereconsidered as 1:2:2 for Co(II) and Ni(II) compounds and1:2:1 for Cu(II) and Zn(II) compounds obtained.

Reference： [1]Dağlı, Özge; Köse, Dursun Ali; İçten, Okan; Avcı, Gülçin Alp; Şahin, Onur [Journal of Thermal Analysis and Calorimetry, 2019, vol. 136, # 4, p. 1467 - 1480]

76
[ 496-41-3 ]
[ 66-71-7 ]
[ 7732-18-5 ]
copper(II) nitrate [ No CAS ]
C₃₀H₂₀CuN₂O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: Benzofuran-2-carboxylic acid With sodium hydrogencarbonate In ethanol; water Stage #2: 1,10-Phenanthroline In ethanol; water for 1h; Stage #3: water; copper(II) nitrate In ethanol at 60℃; for 5h;	General procedure: Firstly, coumarilate salt compounds with natrium cationwere synthesized by 0.005 mol of coumarilic acid dissolvedin a 50:50 (v/v) EtOH/H2O solution in a beakerfollowed by the addition of 0.005 mol of NaHCO3 providingCO2 output. Then, the 1,10-phenanthroline solution(0.005 mol 25 mL H2O) was first added to the salt solutionsand mixed for 1 h in the magnetic stirrer. Finally, themetal-nitrate salts (0.0025 mol) in solid phase wereappended to the main solution in 1:2 ratio concerning thecoumarilate anion and mixed for 5 h at 60 C (Scheme 2,Eq. 2).The final solution was allowed to crystallize at atmosphericpressure by standing at room temperature. Thecrystals precipitated in approximately 20-30 days werecollected by filtration. The metal/ligand/ligand ratio wereconsidered as 1:2:2 for Co(II) and Ni(II) compounds and1:2:1 for Cu(II) and Zn(II) compounds obtained.

Reference： [1]Dağlı, Özge; Köse, Dursun Ali; İçten, Okan; Avcı, Gülçin Alp; Şahin, Onur [Journal of Thermal Analysis and Calorimetry, 2019, vol. 136, # 4, p. 1467 - 1480]

77
[ 496-41-3 ]
benzofuran-2-carbonyl fluoride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With tetramethylammonium trifluoromethanethiolate In dichloromethane Inert atmosphere;	1-3. Procedures of preparation of acyl fluoride 1 General procedure: Method AS3: Under N2 atmosphere, the corresponding carboxylic acid (3.00 mmol) was transferredto a PFA bottle equipped with a stirrer bar. After addition of CH2Cl2 (5.00 mL) to the bottle, the reactionmixture was cooled at 0 °C in ice bath. Then, Deoxo-fluor (0.560 mL, 3.04 mmol) was added to thesolution. The bottle was capped, and the reaction mixture was stirred at 0 °C for 5-30 min (written ateach substrate in parentheses). The reaction was quenched by addition of aqueous NaHCO3. Themixture was extracted with CH2Cl2 (10.0 mL) three times. The combined organic layer was dried overNa2SO4. Solvents were removed under reduced pressure. The crude material was purified by silica gelcolumn chromatography (hexane/AcOEt = 97:3) to give the corresponding acid fluoride.Method BS4: Under N2 atmosphere, the corresponding carboxylic acid (1.00 mmol) was transferredto a PFA bottle equipped with a stirrer bar. To the reaction vessel, Me4N•SCF3 (230 mg, 1.31 mmol)and CH2Cl2 (5.00 mL) were added. Then, the reaction mixture was stirred until completelyconsumption of Me4N•SCF3. The resulting suspension was filtered through a silica gel pad. Solventswere removed under reduced pressure. The crude material was purified by silica gel columnchromatography (hexane/AcOEt = 97:3) to give the corresponding acid fluoride.
	With N,N,N',N'-tetramethyl-1,8-diaminonaphthalene; fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate In tetrahydrofuran at 20℃;
	With (bis-(2-methoxyethyl)amino)sulfur trufluoride In dichloromethane at 0℃; for 1h;

Reference： [1]Ishida, Naoyoshi; Iwamoto, Hiroaki; Sunagawa, Denise Eimi; Ohashi, Masato; Ogoshi, Sensuke [Synthesis, 2021, vol. 53, # 17, p. 3137 - 3143]
[2]Malapit, Christian A.; Bour, James R.; Brigham, Conor E.; Sanford, Melanie S. [Nature, 2018, vol. 563, # 7729, p. 100 - 104]
[3]Kayumov, Muzaffar; Zhao, Jian-Nan; Mirzaakhmedov, Sharafitdin; Wang, Dong-Yu; Zhang, Ao [Advanced Synthesis and Catalysis, 2020, vol. 362, # 4, p. 776 - 781]

78
[ 496-41-3 ]
[ 646-25-3 ]
N,N′-(decane-1,10-diyl)bis(benzofuran-2-carboxamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 12h;	in a round bottom flask, 0.400 g of benzofuran-2-carboxylic acid, 0.193 g of decanediamine, 0.473 g of EDCI, 0.027 g of DMAP, and 10 mL of anhydrous dichloromethane were successively added, and the mixture was stirred at room temperature for 12 hours.A white solid precipitated, suction filtered, and then dichloromethane (2×2.5 mL)Wash with water (3 x 5 mL), dry,Obtained 0.220 g of a white solid.The yield was 43% (see Figure 25 for the synthetic route and Figure 26 for the characterization map).
43%	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]Patent: CN110229110,2019,A .Location in patent: Paragraph 0112-0113
[2]Molecules,2019,vol. 24

79
[ 496-41-3 ]
[ 1353016-70-2 ]
LDT-Ahx-K(Mtt)-Ahx-EEEAAAVVV-K(lauryl)-NH2 [ No CAS ]
benzofuran-2-carboxylic acid-LDT-Ahx-K(DBCO)-Ahx-EEEAAAVVV-K(lauryl)-NH2 [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Low loading (0.35 mmol/g) rink amide MBHA resin was Fmoc deprotected (20% 4- methypiperidine in DMF) before adding Fmoc-K(Mtt)-OH, 2 equiv., HBTU (1.9 equiv.) and DIEA (4 equiv.), which was allowed to shake for 4 hours at room temperature (rt). The Mtt protecting group was then removed as described above before adding lauric acid using 4 equiv., HBTU (3.9 equiv.) and DIEA (8 equiv.) in DMF for 6 hours. The remainder of the base peptide was then synthesized using automated peptide synthesis resulting in H2N-LDT- Ahx-K(Mtt)-Ahx-EEEAAAVVV-K(lauryl) (SEQ ID NO: 13) that was tested for completion by test cleavage (MS - calc. 1918 m/z, obs. 1918 m/z). Benzofuran-2-carboxylic acid (X2) was then added using 4 equiv., HBTU (3.9 equiv.) and DIEA (8 equiv.) in DMF for 4 h and the mass was confirmed by test cleavage (MS - calc. 2053 m/z, obs. 2053 m/z). The Mtt protecting group was then removed and DBCO-Acid (Click Chemistry Tools) 2 equiv., HBTU (1.9 equiv.) and DIEA (4 equiv.) was then added in DMF for 4 h to overnight and the mass of the resulting final product was confirmed by test cleavage (MS - calc. 2339 m/z, obs. 2340 m/z). LDT= leucine-aspartic acid-threonine tripeptide.

Reference： [1]Patent: WO2019/200298,2019,A1 .Location in patent: Page/Page column 27; 28; 29

80
[ 496-41-3 ]
[ 13324-66-8 ]
N-benzyl-N-cyclopropylbenzofuran-2-carboxamide [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 18844 - 18848
Angew. Chem.,2019,vol. 131,p. 19020 - 19024,5

81
[ 496-41-3 ]
[ 517-89-5 ]
(R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl benzofuran-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35.7%	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0℃; for 8h;	4.1.3 Synthesis of compounds 6a-6q General procedure: Shikonin (1mmol), benzofuran-2-carboxylic acid derivatives (4a-4q) (3mmol), 4-dimethyaminopyridine (0.5mmol), and N, N′- dicyclohexylcarbodiimide (0.5mmol) were suspended in the anhydrous DCM (10ml). The reaction mixture was stirred for 8h under 0°C. Afterwards, the targeted compounds 6a-6q were purified by column chromatography. 4.1.3.1 (R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl benzofuran-2-carboxylate (6a) Violet powder. Yield: 35.7%. m. p: 88.7-90.3°C. 1H NMR (600MHz, CDCl3): 12.62 (s, 1H, OH), 12.42 (s, 1H, OH), 7.72 (d, J=7.8Hz, 1H, ArH), 7.62 (d, J=6.2Hz, 2H, ArH), 7.49 (t, J=7.9Hz, 1H, ArH), 7.34 (t, J=7.3Hz, 1H, ArH), 7.19 (s, 2H, ArH), 7.15 (s, 1H, ArH), 6.32 (dd, J=6.7, 4.7Hz, 1H, CH-O), 5.22 (t, J=7.3Hz, 1H, CH=C), 2.81-2.76 (m, 1H, CH2), 2.65 (dt, J=14.9, 7.4Hz, 1H, CH2), 1.69 (s, 3H, CH3), 1.62 (s, 3H, CH3). 13C NMR (151MHz, CDCl3): 177.38, 175.85, 168.34, 167.81, 158.32, 155.97, 147.43, 144.86, 136.63, 133.25, 133.06, 131.51, 128.03, 126.85, 124.00, 122.96, 117.41, 114.70, 112.50, 111.88, 111.65, 70.54, 32.99, 25.84, 18.05. HRMS (ESI) m/z: 455.1102 [M+Na]+ (calcd for 455.1101, C25H20NaO7).

Reference： [1]Kong, Ling-Yi; Leng, Jia-Fu; Lian, Bao-Ping; Shao, Yu-Ying; Xia, Yuan-Zheng; Yin, Yong [European Journal of Medicinal Chemistry, 2020, vol. 190]

82
[ 496-41-3 ]
[ 3416-24-8 ]
N-(2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2Hpyran-3-yl)benzofuran-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: Benzofuran-2-carboxylic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In acetonitrile Stage #2: 2-amino-2-deoxyglucose In acetonitrile at 30℃; for 0.833333h;

Reference： [1]Cao, Zhi-Ling; Liu, Shu-Hao; Liu, Wei-Wei; Liu, Xiu-Jian; Ren, Shu-Ting; Shi, Da-Hua; Wang, Lei; Wang, You-Xian; Wu, Yu-Ran [Heterocyclic Communications, 2019, vol. 25, # 1, p. 162 - 166]

83
[ 496-41-3 ]
[ 5440-00-6 ]
8-(benzofuran-2-yl)-1,3-dimethyl-1H-purine-2,6-(3H,7H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With hydrogenchloride; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In 1,4-dioxane; lithium hydroxide monohydrate at 20℃;	2 8-(benzofuran-2-yl)-1,3-dimethyl-1H-purine-2,6-(3H,7H)-dione (I-1-2) Combine 1mmol of intermediate 5,6-diamino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione and 1mmol of EDCI (1-ethyl-(3-dimethylaminopropyl) Base) carbodiimide hydrochloride) was added to the reaction flask in turn, 5mL dioxane and 5mL water were added, 1mmol of benzo[b]furan-2-carboxylic acid was added under stirring at room temperature, and added dropwise to the reaction solution Adjust pH with 1M HCl aqueous solution=56,Reaction at room temperature with stirring to generate amide compound;TLC detection reaction (developer: chloroform: methanol = 20:1),After the reaction is completed, add 1 mmol of NaOH solid and 1 mL of water, and heat to reflux for reaction;TLC detection reaction (developer: chloroform: methanol = 20:1),After the completion of the reaction, the pH was adjusted to 5-6 with 1M aqueous hydrochloric acid solution, and a large amount of solid was precipitated, which was filtered and washed with water and recrystallized from ethanol to obtain compound 8-(benzofuran-2-yl)-1,3-dimethyl-1H-purine- 2,6-(3H,7H)-dione, the yield is 55%.
	Multi-step reaction with 2 steps 1.1: N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride / 1,4-dioxane; lithium hydroxide monohydrate / 0.5 h / 20 °C 1.2: pH 5 - 6 2.1: sodium hydroxide / 1,4-dioxane; lithium hydroxide monohydrate / 1 h / 110 °C

Reference： [1]Current Patent Assignee: SHANDONG XINHUA PHARMACEUTICAL CO., LTD. - CN112209930, 2021, A Location in patent: Paragraph 0184-0187
[2]Li, Jiarong; Meng, Zihui; Wang, Hongyi; Wang, Yiyun; Xu, Haojie; Xu, Zhibin; Xue, Min; Zheng, Zhonghui [Chemical Biology and Drug Design, 2022]

84
[ 496-41-3 ]
[ 36887-98-6 ]
C₁₈H₁₆N₂O₂ [ No CAS ]

Reference： [1]Archiv der Pharmazie,2021,vol. 354

85
[ 496-41-3 ]
C₁₂H₁₃N₃O*ClH [ No CAS ]
N-(3-(1H-imidazole-1-yl)-1-oxo-1-phenylpropan-2-yl)benzofuran-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66.3%	Stage #1: Benzofuran-2-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: C₁₂H₁₃N₃O*ClH With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	4.7. General procedure for the synthesis of compounds (14a-j) General procedure: To a solution of acid 13a-j (1.0 equiv.) in DMF, HOBt (1.1 equiv.)and EDCI (1.1 equiv.) were added and the mixturewas stirred for 1 hat room temperature. Then the amino salt 12a (1.1 equiv.) and DIEA(2.2 equiv.) were added. The reaction was stirred and monitoredwith TLC. The mixture was poured into water and extracted withethyl acetate three times. The combined organic layers were driedover Na2SO4 and evaporated in a vacuum [16]. The crude productwas purified by silica gel column chromatography(CH3OH:CH2Cl2 40:1) to afford target compounds 14a-j.

Reference： [1]Cheng, Maosheng; Cui, Hengxian; Jiang, Hong; Li, Song; Liu, Lei; Su, Xin; Sun, Yin; Wu, Tianxiao; Yin, Wenbo; Zhang, Yuxin; Zhao, Dongmei; Zhao, Liyu; Zheng, Yang [European Journal of Medicinal Chemistry, 2021, vol. 225]

86
N-(3-aminophenyl)-4-nitrobenzenesulfonamide [ No CAS ]
[ 496-41-3 ]
N-(3-((4-nitrophenyl)sulfonamido)phenyl)benzofuran-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.8%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In tetrahydrofuran at 20℃; for 3h;	4.1.7 Synthesis of compounds 9a-9g General procedure: HATU (58mg, 1.8mmol) and DIPEA (44μL, 3.0mmol) were added to a solution of the corresponding carboxylic acid derivatives (1.2mmol) in THF (1mL) at rt. Then, compound 8 (1.0mmol) was added and the solution was stirred for approximately 3h. The solvent was removed, the residue was dissolved with ethyl acetate, washed by water and saturated using ammonium chloride solution. The organic phases were dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by flash column chromatography to obtain the compounds 9a-9g. 4.1.7.1 N-(3-((4-nitrophenyl)sulfonamido)phenyl)benzofuran-2-carboxamide (9a) White solid, yield: 80.8%, 1H NMR (600MHz, Acetone-d6) δ 9.88 (s, 1H), 9.46 (s, 1H), 8.39 (d, J=8.1Hz, 2H), 8.14 (d, J=8.3Hz, 2H), 7.93 (s, 1H), 7.80 (d, J=7.8Hz, 1H), 7.64 (s, 1H), 7.62 (d, J=8.1Hz, 1H), 7.59 (d, J=8.3Hz, 1H), 7.50 (t, J=7.7Hz, 1H), 7.36 (t, J=7.4Hz, 1H), 7.28 (t, J=8.0Hz, 1H), 7.01 (d, J=7.9Hz, 1H). 13C NMR (150MHz, Acetone-d6) δ 156.68, 154.91, 150.37, 149.01, 145.32, 139.50, 137.60, 129.64, 128.70, 127.63, 127.21, 124.33, 123.86, 122.84, 116.81, 116.61, 112.74, 111.74, 110.81. ESI-HRMS [M+Na]+ calcd for C21H16N3O6SNa: 460.3574, found: 460.3574.
80.8%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In tetrahydrofuran at 20℃; for 3h;	4.1.7 Synthesis of compounds 9a-9g General procedure: HATU (58mg, 1.8mmol) and DIPEA (44μL, 3.0mmol) were added to a solution of the corresponding carboxylic acid derivatives (1.2mmol) in THF (1mL) at rt. Then, compound 8 (1.0mmol) was added and the solution was stirred for approximately 3h. The solvent was removed, the residue was dissolved with ethyl acetate, washed by water and saturated using ammonium chloride solution. The organic phases were dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by flash column chromatography to obtain the compounds 9a-9g. 4.1.7.1 N-(3-((4-nitrophenyl)sulfonamido)phenyl)benzofuran-2-carboxamide (9a) White solid, yield: 80.8%, 1H NMR (600MHz, Acetone-d6) δ 9.88 (s, 1H), 9.46 (s, 1H), 8.39 (d, J=8.1Hz, 2H), 8.14 (d, J=8.3Hz, 2H), 7.93 (s, 1H), 7.80 (d, J=7.8Hz, 1H), 7.64 (s, 1H), 7.62 (d, J=8.1Hz, 1H), 7.59 (d, J=8.3Hz, 1H), 7.50 (t, J=7.7Hz, 1H), 7.36 (t, J=7.4Hz, 1H), 7.28 (t, J=8.0Hz, 1H), 7.01 (d, J=7.9Hz, 1H). 13C NMR (150MHz, Acetone-d6) δ 156.68, 154.91, 150.37, 149.01, 145.32, 139.50, 137.60, 129.64, 128.70, 127.63, 127.21, 124.33, 123.86, 122.84, 116.81, 116.61, 112.74, 111.74, 110.81. ESI-HRMS [M+Na]+ calcd for C21H16N3O6SNa: 460.3574, found: 460.3574.

Reference： [1]Feng, Kai-Rui; Gao, Dingding; Huang, Cheng; Huang, Min; Lan, Xiaojing; Lin, Guo-Qiang; Shi, Xin-Wei; Tang, Shuai; Tian, Ping; Yuan, Liang; Zhang, Fu-Mao [Bioorganic Chemistry, 2022, vol. 121]
[2]Feng, Kai-Rui; Gao, Dingding; Huang, Cheng; Huang, Min; Lan, Xiaojing; Lin, Guo-Qiang; Shi, Xin-Wei; Tang, Shuai; Tian, Ping; Yuan, Liang; Zhang, Fu-Mao [Bioorganic Chemistry, 2022, vol. 121]

87
[ 496-41-3 ]
[ 33977-38-7 ]
[ 600709-85-1 ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: Benzofuran-2-carboxylic acid With dmap; N,N-dicyclohexylcarbodiimide In dichloromethane at 20℃; for 0.166667h; Stage #2: 1-bromo-4-aminobutane In dichloromethane at 20℃;	Synthesis of compound 7 A mixture of benzofuran-2-carboxylic acid (0.174 g, 1.070 mmol) and 4-dimethylaminopyridine (0.156 g, 1.280 mmol) were dissolved in dry dichloromethane (10 mL). A solution of N, N-dicyclohexylcarbodiimide (0.263 g, 1.275 mmol) in CH2Cl2 (5 mL) was added slowly dropwise to the reaction flask. After stirring at room temperature for 10 min, 4-bromobutan-1-amine hydrobromide (0.25 g, 1.07 mmol) was added and the mixture was stirred for 6 h at room temperature. The resulting suspension was filtered through a pad of celite and washed with CH2Cl2 (3 × 30 mL) and the filtrate evaporated. The crude product was purified by silica gel chromatography with hexane/ethyl acetate (v/v = 5/1-1/1) to yield 7 as a white solid (0.233 g, 74%). 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 7.8 Hz, 1H), 7.54 - 7.45 (m, 2H), 7.45 - 7.39 (m, 1H), 7.33 - 7.27 (m, 1H), 6.70 (s, 1H), 3.61 - 3.44 (m, 4H), 2.05 - 1.89 (m, 2H), 1.89 - 1.75 (m, 2H). LRMS (ESI) m/z calcd. for C13H15BrNO2+. [M + Na]+: 320.04, found: 320.64.
74%	Stage #1: Benzofuran-2-carboxylic acid With dmap; N,N-dicyclohexylcarbodiimide In dichloromethane at 20℃; for 0.166667h; Stage #2: 1-bromo-4-aminobutane In dichloromethane at 20℃;	Synthesis of compound 7 A mixture of benzofuran-2-carboxylic acid (0.174 g, 1.070 mmol) and 4-dimethylaminopyridine (0.156 g, 1.280 mmol) were dissolved in dry dichloromethane (10 mL). A solution of N, N-dicyclohexylcarbodiimide (0.263 g, 1.275 mmol) in CH2Cl2 (5 mL) was added slowly dropwise to the reaction flask. After stirring at room temperature for 10 min, 4-bromobutan-1-amine hydrobromide (0.25 g, 1.07 mmol) was added and the mixture was stirred for 6 h at room temperature. The resulting suspension was filtered through a pad of celite and washed with CH2Cl2 (3 × 30 mL) and the filtrate evaporated. The crude product was purified by silica gel chromatography with hexane/ethyl acetate (v/v = 5/1-1/1) to yield 7 as a white solid (0.233 g, 74%). 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 7.8 Hz, 1H), 7.54 - 7.45 (m, 2H), 7.45 - 7.39 (m, 1H), 7.33 - 7.27 (m, 1H), 6.70 (s, 1H), 3.61 - 3.44 (m, 4H), 2.05 - 1.89 (m, 2H), 1.89 - 1.75 (m, 2H). LRMS (ESI) m/z calcd. for C13H15BrNO2+. [M + Na]+: 320.04, found: 320.64.

Reference： [1]Chen, Zhengping; Fang, Yi; Hu, Qianyue; Huang, Caiyun; Ji, Linyang; Li, Qingming; Liu, Chunyi; Tang, Jie [Bioorganic and Medicinal Chemistry Letters, 2022, vol. 62]
[2]Chen, Zhengping; Fang, Yi; Hu, Qianyue; Huang, Caiyun; Ji, Linyang; Li, Qingming; Liu, Chunyi; Tang, Jie [Bioorganic and Medicinal Chemistry Letters, 2022, vol. 62]

88
[ 496-41-3 ]
4-((E)-3,5-dimethoxy-2-((E)-2-nitrovinyl)styryl)aniline [ No CAS ]
N-(4-((E)-3,5-dimethoxy-2-((E)-2-nitrovinyl)styryl)phenyl)benzofuran-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	Stage #1: 4-((E)-3,5-dimethoxy-2-((E)-2-nitrovinyl)styryl)aniline With N-ethyl-N,N-diisopropylamine; O-(benzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate In dichloromethane at 25℃; for 0.5h; Stage #2: Benzofuran-2-carboxylic acid In dichloromethane at 25℃; for 10h;	Compound 1e (120 mg, 0.368 mmol) and DIPEA (95 mg,0.735 mmol) was dissolved CH2Cl2 (8 mL), then HATU (182 mg,0.478 mmol) was added into the solution. After the mixture wasstirred at 25 C for 30 min, tertiary carboxylic acid (50 mg,0.478 mmol) was added into the mixture, and then it was stirred at25 C for 10 h. After the reaction was completed, the reaction wasadded H2O, then extracted with DCM (45 mL 2). The combinedorganic layer was washed with saturated brine solution, dried overanhydrous Na2SO4, and concentrated to give the yellow solid, thenpurified by column chromatography (gradient elution of PE/DCM10/90 v/v) to obtain compound 1. Compounds 2e31 were obtainedaccording to the similar procedures.
45%	Stage #1: 4-((E)-3,5-dimethoxy-2-((E)-2-nitrovinyl)styryl)aniline With N-ethyl-N,N-diisopropylamine; O-(benzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate In dichloromethane at 25℃; for 0.5h; Stage #2: Benzofuran-2-carboxylic acid In dichloromethane at 25℃; for 10h;	Compound 1e (120 mg, 0.368 mmol) and DIPEA (95 mg,0.735 mmol) was dissolved CH2Cl2 (8 mL), then HATU (182 mg,0.478 mmol) was added into the solution. After the mixture wasstirred at 25 C for 30 min, tertiary carboxylic acid (50 mg,0.478 mmol) was added into the mixture, and then it was stirred at25 C for 10 h. After the reaction was completed, the reaction wasadded H2O, then extracted with DCM (45 mL 2). The combinedorganic layer was washed with saturated brine solution, dried overanhydrous Na2SO4, and concentrated to give the yellow solid, thenpurified by column chromatography (gradient elution of PE/DCM10/90 v/v) to obtain compound 1. Compounds 2e31 were obtainedaccording to the similar procedures.

Reference： [1]Chen, Liu Zeng; Diao, Liang Zhuo; Jiang, Han; Liu, Xin Hua; Ma, Duo; Ruan, Ban Feng; Wang, Yu Meng; Zhang, Xing Xing [European Journal of Medicinal Chemistry, 2022, vol. 236]
[2]Chen, Liu Zeng; Diao, Liang Zhuo; Jiang, Han; Liu, Xin Hua; Ma, Duo; Ruan, Ban Feng; Wang, Yu Meng; Zhang, Xing Xing [European Journal of Medicinal Chemistry, 2022, vol. 236]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	496-41-3	MDL No. :	MFCD00005848
Formula :	C₉H₆O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	OFFSPAZVIVZPHU-UHFFFAOYSA-N
M.W :	162.14	Pubchem ID :	10331
Synonyms :

Num. heavy atoms :	12
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	43.17
TPSA :	50.44 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.58 cm/s

Log Po/w (iLOGP) :	1.35
Log Po/w (XLOGP3) :	2.41
Log Po/w (WLOGP) :	2.13
Log Po/w (MLOGP) :	1.08
Log Po/w (SILICOS-IT) :	1.75
Consensus Log Po/w :	1.74

[ CAS No. 496-41-3 ] {[proInfo.proName]}

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[ 496-41-3 ] Synthesis Path-Upstream 1~4

[ 496-41-3 ] Synthesis Path-Downstream 1~88

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[ 496-41-3 ]

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[ 496-41-3 ]

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Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Log S (ESOL) :	-2.85
Solubility :	0.228 mg/ml ; 0.0014 mol/l
Class :	Soluble
Log S (Ali) :	-3.11
Solubility :	0.125 mg/ml ; 0.000774 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.65
Solubility :	0.363 mg/ml ; 0.00224 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.2

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

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P378
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P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
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P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
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P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
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P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
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[ CAS No. 496-41-3 ] {[proInfo.proName]}

Quality Control of [ 496-41-3 ]

Related Doc. of [ 496-41-3 ]

Product Details of [ 496-41-3 ]

Calculated chemistry of [ 496-41-3 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 496-41-3 ]

Application In Synthesis of [ 496-41-3 ]

[ 496-41-3 ] Synthesis Path-Upstream 1~4

[ 496-41-3 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 496-41-3 ]

Carboxylic Acids

Related Parent Nucleus of [ 496-41-3 ]

Benzofurans

Precautionary Statements-General

Prevention

Response

Storage

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Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 496-41-3 ]

Related Parent Nucleus of
[ 496-41-3 ]