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CAS No. : | 41717-28-6 | MDL No. : | MFCD01659782 |
Formula : | C9H5ClO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ZJDRDTZQVOCKPI-UHFFFAOYSA-N |
M.W : | 180.59 | Pubchem ID : | 38949 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 9 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 46.4 |
TPSA : | 30.21 Ų |
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) : | -4.99 cm/s |
Log Po/w (iLOGP) : | 2.18 |
Log Po/w (XLOGP3) : | 3.39 |
Log Po/w (WLOGP) : | 2.81 |
Log Po/w (MLOGP) : | 1.45 |
Log Po/w (SILICOS-IT) : | 2.87 |
Consensus Log Po/w : | 2.54 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.58 |
Solubility : | 0.047 mg/ml ; 0.00026 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.7 |
Solubility : | 0.0357 mg/ml ; 0.000198 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.85 |
Solubility : | 0.0255 mg/ml ; 0.000141 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.27 |
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P260-P261-P264-P270-P271-P280-P301+P312-P301+P330+P331-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P310-P312-P321-P322-P330-P363-P405-P501 | UN#: | 3261 |
Hazard Statements: | H302-H312-H314-H332 | Packing Group: | Ⅲ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
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. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonia; | b) preparation of benzofuran-2-carboxamide <strong>[41717-28-6]Benzofuran-2-carbonyl chloride</strong> (21.8 g) was added in small portions to an ice cold solution of ammonia (200 ml, d=0.91). Upon completion of the addition the reaction mixture was allowed to reach room temperature and the desired carboxamide formed a precipitate. The solid was collected by filtration, washed with water and dried in vacuo (17.8 g, 91%). IR: (KBr): 1661 cm-1 1 H-NMR (DMSO-d6): 7.35 (t,1H), 7.45 (t,1H), 7.60 (s,1H), 7.65 (d,1H), 7.75 (d,1H), 7.70-8.20 (d,2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | for 0.05h; microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; for 0.5h;Heating / reflux; | Example 2.10; 2-(1-Benzofuran-2-yl)pyrido[3,4-d]pyrimidin-4(3H)-one (C: R=7-aza, R'~1-benzofuran-2-yl); A slurry of 3-aminoisonicotinic acid (1.556 g, 11.3 mmol) and CDI (2.82 g, 17.4 mmol) in dmf (20 mL) was heated to 40C for 0.5 h then cooled. Concentrated aqueous ammonia (50 mL) was added and the mixture was stirred for 15 min then extracted with ethyl acetate. Removal of the solvent gave a solid which was dissolved in pyridine (20 mL), 1-benzofuran-2-carbonyl chloride (from benzo[ib]furan-2-carboxylic acid; 2.006 g, 12.4 mmol) was added and the mixture was refluxed for 0.5 h, poured onto ice and filtered to give theintermediate amide (E: R=4-aza, R'=1-benzofuran-2-yl). The intermediate amide was refluxed in 5% aqueous KOH (20 mL)/EtOH (10 ml_) for 0.5 h to give the product (0.303 g, 10%) as a solid. 1H NMR (DMSO-d6) 5 ppm 13.07 (bs, 1H), 9.15 (d, 1H, J=0.8 Hz), 8.68 (d, 1H, J=5.1 Hz), 8.11 (d, 1H, J=0.8 Hz), 7.98 (dd, 1H, J=5.1, 0.8 Hz), 7.84 (dd, 1H, J=7.5, 0.8 Hz), 7.77 (dd, 1H, J=8.3, 0.8 Hz), 7.51 (ddd, 1H, J=8.3, 7.3, 1.2 Hz), 7.38 (td, 1H, J=7.5, 0.8 Hz). ACPI-MS Found: [M+H]+= 264. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With pyridine; for 1h;Heating / reflux; | 3. Ester route fScheme 3); A solution of an anthranilate ester (F) and an acid chloride (R'COCI) was refluxed in pyridine or other suitable solvent with a catalytic amount of 4-A/,A/-dimethylaminopyridine or other suitable catalyst, followed by quenching the reaction with ice and isolation of the intermediate ester (G). This was then heated under reflux in methanolic ammonia for a specified time, and solvent was removed until the entire quinazolinone product (C) had precipitated from solution.; Example 3.1; 2-(1-Benzofuran-2-yl)[3,2-djpyrimidin-4(3W)-one (C: R=5-aza, R'=benzofuran-2-yl); The intermediate ester (G: R=6-aza, R'=benzofuran-2-yl) was synthesised by refluxing methyl 3-amino-2-pyridinecarboxylate (0.250 g, 1.64 mmol) and 1-benzofuran-2-carbonyl chloride (from benzo[6]furan-2-carboxylic acid, 0.300 g, 1.85 mmol) in pyridine (10 mL) for 1 h, to give the ester (0.329 g, 68%). The intermediate ester (0.179 g, 0.604 mmol) was refluxed in methanolic ammonia (7 M, 15 mL) for 23 h to give 2-(1-benzofuran-2-yl)pyrido[3,2-d]pyrimidin-4(3H)-one (0.126 g, 79%). 1H NMR (DMSO-d6) 8 ppm 13.02 (bs, 1H), 8.79 (dd, 1H, J=4.3, 1.4 Hz), 8.19 (dd, 1H, J=8.3, 1.4 Hz), 8.10 (d, 1H, J=0.3 Hz), 7.80-7.86 (m, 2H), 7.75 (dd, 1H, J=8.4, 0.4 Hz), 7.51 (ddd, 1H, J=8.3, 7.3, 1.2 Hz), 7.37 (td, 1H, J=7.5, 0.6 Hz). ACPI-MS Found: [M+H]+= 264. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44.2% | With triethylamine; In 1,4-dioxane; at 0℃; | Benzofuran-2-carboxylic acid [1- (3, 4-dimethoxy-phenyl)- cyclohexylmethyl]-amide.; <P> [00175] C- [l- (3, 4-Dimethoxy-phenyl)-cyclohexyl]-methylamine (276 mg, 1.12 mmol) and <strong>[41717-28-6]Benzofuran-2-carbonyl chloride</strong> (223 mg, 1.23 mmol) were dissolved in 6 mL of 1,4-dioxane containing triethylamine (312 pL, 2. 24 mmol) at 0C. The reaction mixture was evaporated to dryness, redissolved in dichloromethane, and extracted with 1M hydrochloric acid, 1M sodium hydroxide, and a saturated aqueous solution of sodium chloride. The organic layer dried over sodium sulfate and evaporated to dryness. The crude product was then purified by column chromatography on silica gel using a gradient of 0-20 % ethyl acetate in hexanes. The pure fractions were combined and evaporated to dryness to yield a white solid (195 mg, 0.496 mmol, 44.2 %). ESI-MS m/z calc. 393.2, found 394.2 (M+1) +. Retention time of 2.96 minutes. 1H NMR (400 MHz, CD3CN) 6 1.45-2. 20 (m, 10H), 3.48 (d, J = 6.5 Hz, 2H), 3.80 (s, 3H), 3.83 (s, 3H), 6.68 (s, 1H), 6.92-7. 02 (m, 3H), 7.30- 7.38 (m, 2H), 7.42-7. 49 (m, 1H), 7.51-7. 55 (m, 1H), 7.72 (d, J = 7.8 Hz, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78.0% | With triethylamine; In 1,4-dioxane; for 16h; | EXAMPLE 2; Preparation of Exemplary Compounds of Formula I; Benzofuran-2-carboxylic acid [1- (3, 4-dimethoxy-phenyl) - cyclopentylmethyl]-amide.; <P> [00174] C- [l- (3, 4-Dimethoxy-phenyl)-cyclopentyl]-methylamine; (141 mg, 0.600 mmol) was dissolved in anhydrous 1,4-dioxane (2 mL) containing triethylamine (167 pL, 1.20 mmol). Benzofuran -2-carbonyl chloride (108 mg, 0.600 mmol) was then added and the reaction mixture was allowed to stir for 16 hours. The reaction mixture was filtered, evaporated to dryness, and purified by column chromatography on silica gel using a gradient of 5-50 % ethyl acetate in hexanes. The pure fractions were combined and evaporated to dryness to yield a white solid (0.1775 g, 0.4678 mmol, 78.0 %) ESI-MS m/z calc. 379.5, found 380.2 (M+1) +. Retention time of 3.36 minutes. 1H NMR (400 MHz, DMSO-d6) 6 1.57-2. 03 (m, 8H), 3.46 (d, J = 6.4 Hz, 2H), 3.72 (s, 6H), 6.81-6. 89 (m, 3H), 7.31 (t, J = 7.5 Hz, 1H), 7. 44 (t, J = 7. 8 Hz, 1H), 7. 48 (s, 1H), 7. 60 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.94 (t, J = 6.3 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) b 23.1, 35.3, 47.2, 51.8, 55.5, 109.2, 111.5, 111.6, 111.7, 118. 8, 122.6, 123.6, 126.7, 127.1, 139.3, 147.1, 148.3, 149.1, 154.1, 158.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86.3% | With triethylamine; In 1,4-dioxane; for 15h; | Benzofuran-2-carboxylic acid [2- (3, 4-dimethoxy-phenyl) -2- methyl-propyl]-amide.; 2- (3, 4-Dimethoxy-phenyl) -2-methyl-propylamine (106 mg, 0.506 mmol) and benzofuran-2-carbonyl chloride (90.7 mg, 0.502 mmol) were dissolved in 2 mL of 1,4-dioxane containing triethylamine (139 L, 1.00 mmol). The reaction mixture was stirred for 15 hours, evaporated to dryness, redissolved in dichloromethane, and extracted with 1M hydrochloric acid, 1M sodium hydroxide, and a saturated aqueous solution of sodium chloride. The organic layer dried over sodium sulfate and evaporated to dryness. The crude product was then purified by column chromatography on silica gel using a gradient of 1-30 % ethyl acetate in hexanes. The pure fractions were combined and evaporated to dryness to yield a white solid (153 mg, 0.433 mmol, 86.3 %). ESI-MS m/z calc. 353.2, found 354.2 (M+1) +. Retention time of 2.99 minutes. 1H NMR (400 MHz, CD3CN) 6 1. 38 (s, 6H), 3. 60 (s, 2H), 3. 81 (s, 3H), 3. 83 (s, 3H), 6.85-7. 06 (m, 4H), 7.31-7. 39 (m, 2H), 7.46 (t, J = 8.4 Hz, 1H), 7.52-7. 56 (m, 1H), 7.72 (d, J = 8.2 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With triethylamine; In dichloromethane; at 20℃; | To 1.72 g of 4-bromoaniline was added to 1.89 g of benzofuran-2-carboxylic acid chloride in 35 mL of dichloromethane cooled in ice bath, followed by the addition of 4.9 mL of triethylamine. The reaction was stirred at room temperature overnight and then diluted with dichloromethane. The dichloromethane layer was washed with water, 1N HCl, water and brine, dried over Na2SO4, filtered, and concentrated in vacuo to provide 2.61 g of N-(4-bromophenyl)-1-benzofuran-2-carboxamide as a yellow solid. Yield 72%. m.p. 178-180 C.; MS: 314.1(M-H)-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86.6% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; | To 0.11 g of methyl N-[(4'-amino-1,1'-biphenyl-4-yl)sulfonyl]-N-methyl-D-valinate in 4 mL dichloromethane cooled in ice bath, was added 0.058 g of 2-benzofurancarbonyl chloride, and N,N-diisopropylethylamine (0.15 mL) was dropped in. The reaction was stirred at room temperature overnightand then diluted with dichloromethane. The organic layer was washed with water, 5% HCl, and brine, dried over sodium sulfate, filtered, concentrated, and purified by column chromatography eluting with hexane:ethyl acetate (2:1) to provide 0.13 g of methyl N-({4'-[(1-benzofuran-2-ylcarbonyl)amino]-1,1'-biphenyl-4-yl}sulfonyl)-N-methyl-D-valinate. Yield 86.6%. m.p. 67-69 C. MS: 521.3 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 5h; | To a flame-dried flask was added 4-aminobiphenylsulfonyl fluoride (0.75 g, 3 mmol) and methylene chloride (20 mL). The solution was cooled with an ice bath. <strong>[41717-28-6]Benzofuran-2-carbonyl chloride</strong> (0.54 g, 3 mmol) was added after the addition of N,N-N,N-diisopropylethylamine (1.50 equiv.). The ice bath was removed and the reaction mixture was allowed to warm to room temperature. The reaction proceeded at room temperature for 5 h. The reaction mixture was diluted with aqueous ammonium chloride solution (15 mL) and the precipitate was filtered and washed with aqueous ammonium chloride solution twice and water twice. The resulting solid was dried over vacuum and 1.05 g of N-{4'-[(1-benzofuran-2-ylcarbonyl)amino]-1,1'-biphenyl-4-yl}sulfonyl fluoride was obtained (Yield 89%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With pyridine; In acetonitrile; at 70℃; for 1h; | Preparation of 4-(2,5-Dimethoxy-phenyl)-thiazol-2-ylamine; compound with 1-benzofuran-2-yl-ethanone To a stirred solution of free based 4-(2,5-Dimethoxy-phenyl)-thiazol-2-ylamine (236.2 mg, 1.0 mmol) in acetonitrile (6.0 ml) was added pyridine (0.15 g, 2.00 mmol) and 1-<strong>[41717-28-6]Benzofuran-2-carbonyl chloride</strong> (198.6 mg, 1.1 mmol) and the solution was heated to 70C for 1 hour. After cooling the product was isolated by filtration as a yellow solid (35 % yield, 82.65 mg, 0.35 mmol): LCMS 237 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | 18 Ethyl 7-(2-benzofuran)carbonylheptanoate (49l) Ethyl 7-(2-benzofuran)carbonylheptanoate (49l) Following a procedure analogous to that described above for 49a, but substituting 2-benzofurancarbonyl chloride for benzoyl chloride, the title compound was obtained in 45% yield: 1H NMR (300 MHz, CDCl3) δ7.15-7.65 (m, 5H), 4.02 (q, J=7.2 Hz, 2H), 2.83 (t, J=7.2 Hz, 2H), 2.20(t, J=7.5 Hz, 2H), 1.70 (m, 2H), 1.54 (m, 2H), 1.30 (m, 4H), 1.15 (t, J=7.2 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With dmap; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20 - 30℃;Inert atmosphere; | Under an atmosphere of argon, acid chloride 12 (10.8 mg, 60 mumol) was added in portions to a stirred solution of 11 (24 mg, 50 mumol), Etaunig's base (26 muL, 19 mg, 15 mumol), and DMAP (0.6 mg, 5.0 mumol) in dichloromethane (250 muL) at room temperature. The reaction was stirred for 10 minutes then heated to 30 0C for 20 minutes. The mixture was concentrated under reduced pressure. Flash chromatography (ISCO system, silica, 0-50 % ethyl acetate in hexane) provided 13 (21.3 mg, 87 %) as a solid: LRESIMS m/z 492 [M+H]+, calcd. for C23H20F3N3O4Si 492.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With N-ethyl-N,N-diisopropylamine;dmap; In dichloromethane; at 20℃;Inert atmosphere; | Under an atmosphere of argon, acid chloride 12 (15.0 mg, 82 mumol) was added in portions to a stirred solution of 42 (25 mg, 68 mumol), Etaunig's base (36 muL, 27 mg, 205 mumol), and DMAP (0.8 mg, 8.0 mumol) in dichloromethane (340 muL) at room temperature. The reaction was stirred for 2 hours then quenched by addition of a saturated solution OfNaHCO3 (3 mL). The mixture was extracted with ethyl acetate (3 x 3 mL) and combined extracts washed with brine (3 mL), dried over Na2SO4 and concentrated under reduced pressure. Flash chromatography (ISCO system, silica, 0-50 % ethyl acetate in hexane) provided 43 (33.4 mg, 95 %) as a solid: LRESIMS m/z 510 [M+H]+, calcd. for C26H2IF2N3O4Si 510.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With triethylamine; In 1,4-dioxane; | Example 4Synthesis of Compound 5To a boiling solution of 2.2 g (12 mmol) benzo[b]furan-2-carbonyl chloride in dry dioxane, 3.01 g (10 mmol) 2-amino-3-(2-benzothiazolyl)-6-methyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine and 2.2 ml of triethylamine are added. The reaction mixture was cooled, the precipitate filtered off, washed with dioxane, hot water and methanol. The precipitate was crystallized from pyridine, suspended in boiling methanol and filtered off hot. The target compound was obtained in 61% yield.1H NMR (DMSO-d6, CCl4) delta (ppm): 14.10 (s, NH), 8.10-7.76 (m, 4H, benzene), 7.67 (s, 1H, furan), 7.60-7.37 (m, 4H, benzene), 3.53 (s, 2H), 2.95 (t, 2H), 2.78 (t, 2H), 2.44 (s, 3H).TOF MS m/z [M+H]+446. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With N-ethyl-N,N-diisopropylamine;dmap; In dichloromethane; at 20℃; for 2.5h;Inert atmosphere; | Methyl 4-(N-(benzyloxycarbonyl)benzofuran-2-carboxamido)-2-(4-chlorophenyl)thiophene-3-carboxylate (9). Under an atmosphere of argon, acid chloride 8 (8.9 mg, 49 mumol) was added to a stirred solution of 7 (16.5 mg, 41 mumol), Huenig's base (29 muL, 21 mg, 164 mumol), and DMAP (0.6 mg, 5.0 mumol) in dichloromethane (205 muL) at room temperature. The reaction was stirred for 2.5 h. The mixture was concentrated under reduced pressure. Flash chromatography (ISCO system, silica, 0-50% ethyl acetate in hexane) provided 9 (14.8 mg, 66%) as a solid: LRESIMS m/z 545.8 [M+H]+, calcd. for C29H21Cl1N1O6S1 546.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine;dmap; In dichloromethane; at 20℃; for 2.5h;Inert atmosphere; | Methyl 4-(N-(benzyloxycarbonyl)benzofuran-2-carboxamido)-2-(5-methoxypyrazin-2-yl)thiophene-3-carboxylate (160). Under an atmosphere of argon, acid chloride 159 is added to a stirred solution of 158, Huenig's base, and DMAP in dichloromethane at room temperature. The reaction is stirred for 2.5 h. The mixture is concentrated under reduced pressure. Flash chromatography (ISCO system, silica, 0-50% ethyl acetate in hexane) provides 160. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With N-ethyl-N,N-diisopropylamine; In toluene; at 110℃; for 1h; | General procedure: To a stirred solution of compound 5a (0.20 g, 0.64 mmol) dissolved in toluene (4 mL) at 110 C was added benzo[b]thiophene-2-carboxachloride (0.19 g, 0.96 mmol) and DIEA (0.12 g, 0.96 mmol). The reaction mixture was heated for 2 h and then cooled to room temperature. The reaction mixture was diluted with EtOAc (80 mL) and saturated NaHCO3 aq (80 mL). The organic layer was separated and washed with water (80 mL × 1) and brine (80 mL × 1), and then dried over anhydrous Na2SO4. The crude product was obtained after concentration and recrystalized with EtOAc to afford compound 6a as yellow solid (0.21 g, 69%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With triethylamine; In N,N-dimethyl-formamide; for 24h;Reflux; | General procedure: A solution of 6 (4.4 mmol) was added to a solution containing 3- or 4-aminobenzophenone or (3- or 4- aminoacetophenone) (4.4 mmol) and triethylamine (1.3 ml, 8.8 mmol)in dry DMF. The reaction mixture was refluxed for 24 h and then cooled to room temperature. DMF and excess triethylamine were evaporated under reduced pressure. The residue was extracted with dichloromethane and water; the organic layer was separated then dried over anhydrous sodium sulfate, filtered and evaporated to dryness. The residue was purified using silica gel column chromatography (dichloromethane/diethylether) in a ratio of (993:7) unless otherwise indicated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With sodium ethanolate; In N,N-dimethyl-formamide; for 36h;Reflux; | General procedure: A solution of 6a or 6b (4.4 mmol) was added to a solution containing specified 2-aminobenzophenones or 2-aminoacetophenone (4.4 mmol) and sodium ethoxide (0.6 g,8.8 mmol) in dry DMF. The reaction mixture was refluxed for 36 h, and then cooled to room temperature. DMF was evaporated under reduced pressure and the residue was stirred for 10 min in chloroform followed by purification using silica gel column chromatography (chloroform:methanol) in a ratio of (993:7) unless otherwise indicated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With triethylamine; In N,N-dimethyl-formamide; for 24h;Reflux; | General procedure: A solution of 6 (4.4 mmol) was added to a solution containing 3- or 4-aminobenzophenone or (3- or 4- aminoacetophenone) (4.4 mmol) and triethylamine (1.3 ml, 8.8 mmol)in dry DMF. The reaction mixture was refluxed for 24 h and then cooled to room temperature. DMF and excess triethylamine were evaporated under reduced pressure. The residue was extracted with dichloromethane and water; the organic layer was separated then dried over anhydrous sodium sulfate, filtered and evaporated to dryness. The residue was purified using silica gel column chromatography (dichloromethane/diethylether) in a ratio of (993:7) unless otherwise indicated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With triethylamine; In N,N-dimethyl-formamide; for 24h;Reflux; | General procedure: A solution of 6 (4.4 mmol) was added to a solution containing 3- or 4-aminobenzophenone or (3- or 4- aminoacetophenone) (4.4 mmol) and triethylamine (1.3 ml, 8.8 mmol)in dry DMF. The reaction mixture was refluxed for 24 h and then cooled to room temperature. DMF and excess triethylamine were evaporated under reduced pressure. The residue was extracted with dichloromethane and water; the organic layer was separated then dried over anhydrous sodium sulfate, filtered and evaporated to dryness. The residue was purified using silica gel column chromatography (dichloromethane/diethylether) in a ratio of (993:7) unless otherwise indicated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With dmap; triethylamine; In dichloromethane; at 20℃; for 16h;Inert atmosphere; | General procedure: To a solution of acyl chloride (1.0 equiv, commercially available or prepared from the corresponding acid) and N,N-dimethylpyridin-4-amine (0.1 equiv) in dry CH2Cl2 was added a solution of carbamate (1.0 equiv) or carboxylate (1.0 equiv) and NEt3 (5.0 equiv) in dry CH2Cl2 at rt. The resulting solution was stirred at rt for 16 h (TLC control). The solvent was removed under reduced pressure and the crude product was purified by column chromatography using a sufficient mixture of n-hexane/acetone (v/v) as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With triethylamine; In toluene; for 18h;Reflux; | General procedure: To a solution of benzofurane-2-carbonyl chloride 1 in dry toluene, a solution of corresponding anilines and amino-pyridines 2a-j, 2-aminobenzothiazoles 4a, 4c and 5a and 2-aminobenzimidazoles 4b, 4d and 5b in dry toluene was added dropwise, followed by the addition of Et3N. The mixture was refluxed for several hours. After cooling, the resulting products were filtered off and recrystallized from methanol to obtain benzofurane-2-carboxamides 3a, 3b, 3d-j and 6a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With triethylamine In toluene for 20h; Reflux; | 4.1.2 General method for the preparation of compounds 3a, 3b, 3d-j and 6a-f General procedure: To a solution of benzofurane-2-carbonyl chloride 1 in dry toluene, a solution of corresponding anilines and amino-pyridines 2a-j, 2-aminobenzothiazoles 4a, 4c and 5a and 2-aminobenzimidazoles 4b, 4d and 5b in dry toluene was added dropwise, followed by the addition of Et3N. The mixture was refluxed for several hours. After cooling, the resulting products were filtered off and recrystallized from methanol to obtain benzofurane-2-carboxamides 3a, 3b, 3d-j and 6a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With triethylamine; In toluene; for 24h;Reflux; | General procedure: To a solution of benzofurane-2-carbonyl chloride 1 in dry toluene, a solution of corresponding anilines and amino-pyridines 2a-j, 2-aminobenzothiazoles 4a, 4c and 5a and 2-aminobenzimidazoles 4b, 4d and 5b in dry toluene was added dropwise, followed by the addition of Et3N. The mixture was refluxed for several hours. After cooling, the resulting products were filtered off and recrystallized from methanol to obtain benzofurane-2-carboxamides 3a, 3b, 3d-j and 6a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With triethylamine; In toluene; for 18.0h;Reflux; | General procedure: To a solution of benzofurane-2-carbonyl chloride 1 in dry toluene, a solution of corresponding anilines and amino-pyridines 2a-j, 2-aminobenzothiazoles 4a, 4c and 5a and 2-aminobenzimidazoles 4b, 4d and 5b in dry toluene was added dropwise, followed by the addition of Et3N. The mixture was refluxed for several hours. After cooling, the resulting products were filtered off and recrystallized from methanol to obtain benzofurane-2-carboxamides 3a, 3b, 3d-j and 6a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With triethylamine; In toluene; for 18h;Reflux; | General procedure: To a solution of benzofurane-2-carbonyl chloride 1 in dry toluene, a solution of corresponding anilines and amino-pyridines 2a-j, 2-aminobenzothiazoles 4a, 4c and 5a and 2-aminobenzimidazoles 4b, 4d and 5b in dry toluene was added dropwise, followed by the addition of Et3N. The mixture was refluxed for several hours. After cooling, the resulting products were filtered off and recrystallized from methanol to obtain benzofurane-2-carboxamides 3a, 3b, 3d-j and 6a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With triethylamine; In toluene; for 18h;Reflux; | General procedure: To a solution of benzofurane-2-carbonyl chloride 1 in dry toluene, a solution of corresponding anilines and amino-pyridines 2a-j, 2-aminobenzothiazoles 4a, 4c and 5a and 2-aminobenzimidazoles 4b, 4d and 5b in dry toluene was added dropwise, followed by the addition of Et3N. The mixture was refluxed for several hours. After cooling, the resulting products were filtered off and recrystallized from methanol to obtain benzofurane-2-carboxamides 3a, 3b, 3d-j and 6a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With triethylamine; In toluene; for 16h;Reflux; | General procedure: To a solution of benzofurane-2-carbonyl chloride 1 in dry toluene, a solution of corresponding anilines and amino-pyridines 2a-j, 2-aminobenzothiazoles 4a, 4c and 5a and 2-aminobenzimidazoles 4b, 4d and 5b in dry toluene was added dropwise, followed by the addition of Et3N. The mixture was refluxed for several hours. After cooling, the resulting products were filtered off and recrystallized from methanol to obtain benzofurane-2-carboxamides 3a, 3b, 3d-j and 6a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With triethylamine; In toluene; for 18h;Reflux; | General procedure: To a solution of benzofurane-2-carbonyl chloride 1 in dry toluene, a solution of corresponding anilines and amino-pyridines 2a-j, 2-aminobenzothiazoles 4a, 4c and 5a and 2-aminobenzimidazoles 4b, 4d and 5b in dry toluene was added dropwise, followed by the addition of Et3N. The mixture was refluxed for several hours. After cooling, the resulting products were filtered off and recrystallized from methanol to obtain benzofurane-2-carboxamides 3a, 3b, 3d-j and 6a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With triethylamine; In toluene; for 18h;Reflux; | General procedure: To a solution of benzofurane-2-carbonyl chloride 1 in dry toluene, a solution of corresponding anilines and amino-pyridines 2a-j, 2-aminobenzothiazoles 4a, 4c and 5a and 2-aminobenzimidazoles 4b, 4d and 5b in dry toluene was added dropwise, followed by the addition of Et3N. The mixture was refluxed for several hours. After cooling, the resulting products were filtered off and recrystallized from methanol to obtain benzofurane-2-carboxamides 3a, 3b, 3d-j and 6a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With triethylamine; In toluene; for 18h;Reflux; | General procedure: To a solution of benzofurane-2-carbonyl chloride 1 in dry toluene, a solution of corresponding anilines and amino-pyridines 2a-j, 2-aminobenzothiazoles 4a, 4c and 5a and 2-aminobenzimidazoles 4b, 4d and 5b in dry toluene was added dropwise, followed by the addition of Et3N. The mixture was refluxed for several hours. After cooling, the resulting products were filtered off and recrystallized from methanol to obtain benzofurane-2-carboxamides 3a, 3b, 3d-j and 6a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | To the suspension of 1,2,3,4-tetrahydro-beta-carboline (7, 1.2 mmol) in CH2Cl2 (3 ml) at 0C was added slowly an aqueous solution of 4N NaOH (1.2 mol). After 5 min stirring at 0C, appropriate heterocyclic acid chloride (1.2 mmol) was added dropwise. Mixture was stirred for 15 min at 0C and further stirred at rt for 3 h. Completion of the reaction was monitored by TLC. After completion of the reaction, reaction mixture was diluted with CH2Cl2 and was washed with water. Organic layer was separated and dried over anhydrous sodium sulfate. Solvent was evaporated under reduced pressure and crude product was purified by silica gel (100-200)column chromatography using EtOAc: Hexane as mobile phase to get desired 2-heterocyclecarbonyl substituted 1,2,3,4-tetrahydro-beta-carbolines 9a-m in 63-82% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With triethylamine; In dichloromethane; at 0 - 23℃; | To a solution of <strong>[1446-61-3](+)-dehydroabietylamine</strong>(1.0mmol) and triethylamine (3.0 mmol) in CH2Cl2 (5 mL), a solution of the corresponding acyl chloride (1.10 mmol) in CH2Cl2 (5 mL) was slowly added dropwise via syringe at 0 C. Theresulting reaction mixture was allowed to be warmed and was stirred at 23 C for 1-12 hr based on the reaction?s progress (TLC, MS) before it was quenche dwith an aqueous NH4Cl solution (10 mL). The organic phase was separated and the aqueous phase was extracted with CH2Cl2 (5mL x 3). The combined organic phase was dried over MgSO4 and concentrated under reduced pressure. The resulting crude product was purified via flash columnchromatography (SiO2; isocratic eluent: 20% EtOAc in petroleum ether) to provide the amide product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With triethylamine; In dichloromethane; at 20℃; | 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. Retention factor Rf=0.85 (n-hexane:EtOAc=1:1). Mp=98 C. 1H NMR (300 MHz, CDCl3): delta 7.62 (d,J=1.8 Hz, 2H), 7.49 (s, J=1.8 Hz, 1H), 6.38 (s, 1H), 3.62 (q,J=6.4 Hz, 2H), 3.49 (t, J=6.3 Hz, 2H), 2.21 (quin, J=6.5 Hz, 2H). |
480 mg | With triethylamine; In dichloromethane; at 20℃; | General procedure: Compound 9a (191 mg, 1 mmol) was refluxed in excess of thionyl chloride (3 mL) overnight. Excess of thionyl chloride was evaporated and 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 diluted with CH2Cl2 and sequentially 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 chromatography with n-hexane/ethyl acetate (EtOAc) = 4:1 to obtain 10a, (236 mg, 76%) as white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; for 2h;Reflux; Inert atmosphere; | General procedure: A 15 mL two-neck round bottom flask equipped with a magnetic stirrer bar, a septum and nitrogen tee connected to an argon source was charged with Pd(PPh3)4 (5 mol%), CuI (10 mol%) and 1 mL of THF. Then, 2 (1.0 mmol), acyl chloride (2.0 mmol) and 6 mL of THF was added into the reaction mixture. After the reaction mixture was refluxed for 2 h and then cooled to room temperature, the mixture was quenched with water. The reaction mixture was extracted with 20 mL of ether twice, dried over anhydrous MgSO4 and chromatographed on SiO2 column. Elution with n-hexane and dichloromethane (7:3) provided 3,3-difluoro-2-trialkylsilyl-1-(phenyl)prop-2-en-1-one 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With triethylamine In dichloromethane at 20℃; for 5h; | Synthesis of substrate 1a from the acid chloride General procedure: To a solution of benzofuran-2-carbonyl chloride (1.0 equiv) in DCM (0.1 M), was added 8-aminoquinoline (8-AQ, 1.1 equiv) and NEt3 (2 equiv). The resulting reaction mixture wasallowed to stir at rt for 5 h, after which it was diluted with DCM and washed with H2O (3x).The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure.Purification by column chromatography (0-2% MeOH in DCM) afforded the desired product. |
373 mg | With dmap; triethylamine In dichloromethane at 20℃; for 3h; Inert atmosphere; | |
With triethylamine In dichloromethane at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With aluminum (III) chloride; ethylaluminum dichloride; In hexane; dichloromethane; at 0℃; for 0.333333h;Inert atmosphere; | General procedure: Ferrocene (0.005 mole; 460 mg) was dissolved in dichloromethane (20 mL) under N2 atmosphere, and the solution was stirred for 10 min. at 0C . Upon addition of furoyl chloride(0.005 mole; 0.25 mL) to this solution, AlCl3(0,005 mole;670 mg) was added and EtAlCl2 (0.005 mole; 2,5 mL) was added dropwise. The reaction mixture was stirred for 20 min.at 0C and hydrolyzed with distilled water (25 mL). The extraction was repeated three times with dichloromethane (3 £25 mL). The combined organic phase was dried with anhydrousNa2SO4 and concentrated under reduced pressure. Finally, the purification of the product was performed with flash column(10:1, Hexane:EtOAc as eluent) chromatography. The yield was31% (isolated 230 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With pyridine; at 20℃; | General procedure: To the key intermediate compounds 49/50 (1 mmol) in pyridine(2 ml), different acid chlorides (1 mmol) were added dropwise andstirred at room temperature for about 30-90 min. After completionof the reaction (as monitored by TLC), the mixturewas poured ontocrushed ice and pH of the solutionwas adjusted to neutral using dil.HCl. The solid separated was isolated by filtration, dried and purifiedby passing through a column packed with silica gel 60-120using 15% ethyl acetate in n-hexane to yield pure target compounds51a-l and 52a-h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With pyridine; at 20℃; | General procedure: To the key intermediate compounds 49/50 (1 mmol) in pyridine(2 ml), different acid chlorides (1 mmol) were added dropwise andstirred at room temperature for about 30-90 min. After completionof the reaction (as monitored by TLC), the mixturewas poured ontocrushed ice and pH of the solutionwas adjusted to neutral using dil.HCl. The solid separated was isolated by filtration, dried and purifiedby passing through a column packed with silica gel 60-120using 15% ethyl acetate in n-hexane to yield pure target compounds51a-l and 52a-h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With pyridine; In dichloromethane; at 20℃; | General procedure: To a solution of 2-phenylpiperazine or piperazine (1.0 mmol) in CH2Cl2 (30 mL),benzofurane-2-carbonyl chloride (2.4 mmol) and pyridine(3.0 mmol) were added. The reaction mixture was stirring at roomtemperature until TLC showed that all the starting material hadreacted. The reaction mixture was evaporated to dryness to obtainthe corresponding diacyl derivative. Column chromatography gavethe pure compound in high yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With pyridine; In dichloromethane; at 20℃; | General procedure: To a solution of 2-phenylpiperazine or piperazine (1.0 mmol) in CH2Cl2 (30 mL),benzofurane-2-carbonyl chloride (2.4 mmol) and pyridine(3.0 mmol) were added. The reaction mixture was stirring at roomtemperature until TLC showed that all the starting material hadreacted. The reaction mixture was evaporated to dryness to obtainthe corresponding diacyl derivative. Column chromatography gavethe pure compound in high yield.1,4-Bis(benzofurane-2-carbonyl)-2-phenylpiperazine (75).The product was obtained as a solid and purified by column usingchromatography dichloromethane-methanol (60:1) as eluent(374 mg, 83% yield), mp 159e162 C. 1H NMR (500 MHz, DMSO-d6)d 7.79e7.74 (m, 2H), 7.69e7.64 (m, 2H), 7.54e7.24 (m, 11H),5.98e5.74 (m, 1H), 5.01e4.75 (m, 1H), 4.55e4.38 (m, 1H), 4.36e4.08(m, 2H), 3.88e3.42 (m, 2H). 13C RMN (125 MHz, DMSO-d6) d 160.0,159.3, 154.0, 153.9, 147.8, 128.6, 127.3, 126.7, 126.6, 126.5, 123.7,122.5, 111.8, 111.3. HRMS (m/z): calcd for C28H22N2O4Na 473.1472[MNa]; found 473.1464. |
Tags: 41717-28-6 synthesis path| 41717-28-6 SDS| 41717-28-6 COA| 41717-28-6 purity| 41717-28-6 application| 41717-28-6 NMR| 41717-28-6 COA| 41717-28-6 structure
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P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
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. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
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. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
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. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
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: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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