* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With potassium carbonate; copper(II) iodide In dimethyl sulfoxide at 110℃; for 4 h; Inert atmosphere
General procedure: A two-neck round bottom flask was charged with amagnetic stirrer, evacuated and backfilled with argon. 2-iodobenzamide ( 0.5mmol, 124 mg), aniline or α-substituted benzylamine (1.0 mmol), K2CO3(1.0 mmol, 138 mg) and CuBr2 (0.05mmol, 11 mg) in DMSO (5 mL) under argon atmosphere. The mixture was allowed tostir under argon atmosphere at 110 C for 4 h.The mixture was concentrated with the aid of a rotary evaporator, and theresidue was purified by column chromatography on silica gel using petroleumether/ethyl acetate (2:1) as eluent to provide the product 2-9.
With Triethoxysilane; [(2,5-F2C6H2-CH=N-C10H6)Co(III)(H)(PMe3)2] In tetrahydrofuran at 60℃; for 24 h; Schlenk technique
General procedure: To a 25 mL Schlenk tube containing a solution of 2 in 2 mL of THF was added amide (1.0 mmol) and (EtO)3SiH (0.50 g, 3.0 mmol). The reaction mixture was stirred at 60 °C until there was no amide left (monitored by TLC and GC–MS). The product was purified according to literature procedures by Beller
71%
With Triethoxysilane; [cis-Fe(H)(SPh)(PMe3)4] In tetrahydrofuran at 60℃; for 24 h; Inert atmosphere
General procedure: To a 25ml Schlenk tube containing a solution of 1 in 2ml of THF was added amide (1.0 mmol) and (EtO)3SiH (0.50 g, 3.0 mmol). The reaction mixture was stirred at 60 °C until there was no amide left (monitored by TLC and GC-MS). The product was purified according to literature procedures by Beller [27].
Reference：
[1] Tetrahedron Letters, 1986, vol. 27, # 20, p. 2203 - 2206
[2] Catalysis Communications, 2019, p. 72 - 75
[3] Catalysis Communications, 2016, vol. 86, p. 148 - 150
[4] Dalton Transactions, 2018, vol. 47, # 12, p. 4352 - 4359
[5] Journal of Organic Chemistry, 1965, vol. 30, p. 617 - 620
[6] Synthesis, 1983, # 2, p. 142 - 143
3
[ 609-67-6 ]
[ 3930-83-4 ]
Reference：
[1] Journal of Organic Chemistry, 1986, vol. 51, # 22, p. 4303 - 4307
[2] American Chemical Journal, 1899, vol. 21, p. 290
[3] Tetrahedron, 2000, vol. 56, # 27, p. 4777 - 4792
[4] Patent: US4279887, 1981, A,
[5] Organic and Biomolecular Chemistry, 2014, vol. 12, # 26, p. 4571 - 4575
[6] Chemical Communications, 2014, vol. 50, # 51, p. 6797 - 6800
[7] Organic and Biomolecular Chemistry, 2015, vol. 13, # 21, p. 5880 - 5884
[8] Chinese Chemical Letters, 2016, vol. 27, # 6, p. 827 - 831
4
[ 88-67-5 ]
[ 3930-83-4 ]
Reference：
[1] Journal of Organic Chemistry, 2018, vol. 83, # 6, p. 3339 - 3347
[2] Organic Letters, 2002, vol. 4, # 3, p. 351 - 354
[3] Organic Letters, 2011, vol. 13, # 3, p. 518 - 521
[4] Synthesis, 1983, # 2, p. 142 - 143
[5] Tetrahedron, 2000, vol. 56, # 27, p. 4777 - 4792
[6] Organic and Biomolecular Chemistry, 2014, vol. 12, # 26, p. 4571 - 4575
[7] Chemical Communications, 2014, vol. 50, # 51, p. 6797 - 6800
[8] Organic and Biomolecular Chemistry, 2015, vol. 13, # 21, p. 5880 - 5884
[9] Chinese Chemical Letters, 2016, vol. 27, # 6, p. 827 - 831
With hydrogenchloride In sodium hydroxide; diethyl ether
EXAMPLE 2 [125 ](R)-N-[(1-Ethyl-2-pyrrolidinyl)-5-iodo-2-methoxybenzamide A solution of (R)-N-[(1-ethyl-2-pyrrolidinyl)methyl[-2-methoxy-5-tri-n-butyltinbenzamide (15 μg, 22 nmol) in diethylether (10 μL) was mixed with 10.4 mCi of Na125 I (3.2 μg, 22 nmol) in 0.001N NaOH (29 μL). Hydrochloric acid (0.1N, 10 μL) was added followed by the addition of an aqueous solution (5 μL) of sodium N-chloro-4-methylbenzene sulfonamide (16 μg, 70 nmol). After 10 min. at 20° C., NaOH (2N, 20 μL) was added. Extraction with ether (2*150 μL) gave 7.2 mCi of the desired iodobenzamide. Specific activity 590 Ci/mmol, radiochemical yield 70percent.
Reference：
[1] Journal of Chemical Sciences, 2013, vol. 125, # 1, p. 71 - 83
12
[ 64-17-5 ]
[ 3930-83-4 ]
[ 938-73-8 ]
[ 64055-53-4 ]
Reference：
[1] European Journal of Organic Chemistry, 2018, vol. 2018, # 39, p. 5382 - 5388
13
[ 3930-83-4 ]
[ 77152-08-0 ]
[ 360-64-5 ]
Reference：
[1] Journal of Organic Chemistry, 2013, vol. 78, # 22, p. 11126 - 11146
[2] Organic Process Research and Development, 2014, vol. 18, # 8, p. 1020 - 1026
With Triethoxysilane; [(2,5-F2C6H2-CH=N-C10H6)Co(III)(H)(PMe3)2]; In tetrahydrofuran; at 60℃; for 24h;Schlenk technique;
General procedure: To a 25 mL Schlenk tube containing a solution of 2 in 2 mL of THF was added amide (1.0 mmol) and (EtO)3SiH (0.50 g, 3.0 mmol). The reaction mixture was stirred at 60 C until there was no amide left (monitored by TLC and GC-MS). The product was purified according to literature procedures by Beller
71%
With Triethoxysilane; [cis-Fe(H)(SPh)(PMe3)4]; In tetrahydrofuran; at 60℃; for 24h;Inert atmosphere;
General procedure: To a 25ml Schlenk tube containing a solution of 1 in 2ml of THF was added amide (1.0 mmol) and (EtO)3SiH (0.50 g, 3.0 mmol). The reaction mixture was stirred at 60 C until there was no amide left (monitored by TLC and GC-MS). The product was purified according to literature procedures by Beller [27].
With caesium carbonate; copper(I) bromide In dimethyl sulfoxide at 80℃; for 4h; Inert atmosphere;
General Procedure for the Preparation of Compound 3
To a solution of 1 (1.5 g, 6.1 mmol, 1 eq) in DMSO (6 mL) was added 2 (1.1 g, 9.1 mmol, 1.5 eq), cesium carbonate (4.0 g, 12.2 mol, 2.0 eq) and copper (I) bromide (86 mg, 0.6 mmol, 0.1 eq). The mixture was stirred at 80 °C for 4 h. The mixture was diluted with water (30 mL). The solid precipitated was collected and dried to give 1.3 g 3 (grey solid, 96%). MS (ESI) m/z: 223 [M+H]+
72%
With potassium <i>tert</i>-butylate In dimethyl sulfoxide at 20℃; for 3h; Irradiation;
With potassium carbonate; In dimethyl sulfoxide; at 110℃; for 8h;
General procedure: To a 10 mL reaction tube were added MCM-41-L-Proline-CuBr(135 mg, 0.1 mmol), 2-halobenzamide 1 (1.0 mmol), benzylamine derivative 2 (2.0 mmol), K2CO3 (3.0 mmol), and DMSO (3 mL). The reaction mixture was stirred at 110 or 120 C under air for 6-12 h.After being cooled to room temperature, the reaction mixture was diluted with 20 mL of EtOAc, and filtered. The MCM-41-L-Proline-CuBr complex was washed with distilled water (2 5 mL) and ethanol (2 5 mL), and reused in the next run. The filtrate was washed with water (2 10 mL) and dried over MgSO4. After being concentrated in vacuo, the residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc 3:1 to 2:1)to afford the target product 3.
With potassium carbonate In dimethyl sulfoxide at 120℃; for 11h;
4.3. General procedure for the heterogeneous copper(I)-catalyzedsynthesis of quinazolinone derivatives
General procedure: To a 10 mL reaction tube were added MCM-41-L-Proline-CuBr(135 mg, 0.1 mmol), 2-halobenzamide 1 (1.0 mmol), benzylamine derivative 2 (2.0 mmol), K2CO3 (3.0 mmol), and DMSO (3 mL). The reaction mixture was stirred at 110 or 120 °C under air for 6-12 h.After being cooled to room temperature, the reaction mixture was diluted with 20 mL of EtOAc, and filtered. The MCM-41-L-Proline-CuBr complex was washed with distilled water (2 5 mL) and ethanol (2 5 mL), and reused in the next run. The filtrate was washed with water (2 10 mL) and dried over MgSO4. After being concentrated in vacuo, the residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc 3:1 to 2:1)to afford the target product 3.
64%
With oxygen; potassium carbonate; copper(I) bromide In dimethyl sulfoxide at 110℃; for 10h;
With potassium carbonate In dimethyl sulfoxide at 110℃; for 5h;
4.3. General procedure for the heterogeneous copper(I)-catalyzedsynthesis of quinazolinone derivatives
General procedure: To a 10 mL reaction tube were added MCM-41-L-Proline-CuBr(135 mg, 0.1 mmol), 2-halobenzamide 1 (1.0 mmol), benzylamine derivative 2 (2.0 mmol), K2CO3 (3.0 mmol), and DMSO (3 mL). The reaction mixture was stirred at 110 or 120 °C under air for 6-12 h.After being cooled to room temperature, the reaction mixture was diluted with 20 mL of EtOAc, and filtered. The MCM-41-L-Proline-CuBr complex was washed with distilled water (2 5 mL) and ethanol (2 5 mL), and reused in the next run. The filtrate was washed with water (2 10 mL) and dried over MgSO4. After being concentrated in vacuo, the residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc 3:1 to 2:1)to afford the target product 3.4.3.1. 2-Phenylquinazolin-4(3H)-one (3a) [28].White solid. Mp 235-236 °C. 1H NMR (400 MHz, DMSO-d6):δ 12.58 (s, 1H), 8.24-8.18 (m, 3H), 7.86 (t, J 8.4 Hz, 1H), 7.77 (d,J 8.0 Hz, 1H), 7.65e7.51 (m, 4H). 13C NMR (100 MHz, DMSO-d6):δ 162.7, 152.8, 149.2, 135.0, 133.2, 131.8, 129.0, 128.2, 128.0, 127.0,126.3, 121.5.
75%
With oxygen; potassium carbonate; copper(I) bromide In dimethyl sulfoxide at 110℃; for 8h;
With potassium carbonate; copper(II) iodide; In dimethyl sulfoxide; at 110.0℃; for 4.0h;Inert atmosphere;
General procedure: A two-neck round bottom flask was charged with amagnetic stirrer, evacuated and backfilled with argon. 2-iodobenzamide ( 0.5mmol, 124 mg), aniline or alpha-substituted benzylamine (1.0 mmol), K2CO3(1.0 mmol, 138 mg) and CuBr2 (0.05mmol, 11 mg) in DMSO (5 mL) under argon atmosphere. The mixture was allowed tostir under argon atmosphere at 110 C for 4 h.The mixture was concentrated with the aid of a rotary evaporator, and theresidue was purified by column chromatography on silica gel using petroleumether/ethyl acetate (2:1) as eluent to provide the product 2-9.
With sodium azide; <i>L</i>-proline; copper(I) bromide In dimethyl sulfoxide at 80℃;
4.2. General procedure for preparation of quinazolin-4(3H)-ones (5) and pyrido[2,3-d]pyrimidin-4(3H)-ones (7)
General procedure: To a solution of 2-iodobenzamide (3) or 2-bromonicotinamide (6) (2.0 mmol) in DMSO (3 mL), was added aldehyde (2.2 mmol), NaN3 (260 mg, 4.0 mmol), CuBr (29 mg, 0.2 mmol), and l-proline (46 mg, 0.4 mmol). The reaction mixture was stirred at 80 °C under air. After disappearance of the reactant (monitored by TLC), water (30 mL) was added to the mixture, and then extracted with ethyl acetate (15 mL) for three times. The extraction was washed with saturated NaCl solution, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using petroleum ether/ethyl acetate (10:1 to 3:1) as the eluent to give the desired products 5 or 7.
2-(2,6-dimethylphenyl)quinazolin-4(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
50%
With sodium azide; L-proline; copper(I) bromide; In dimethyl sulfoxide; at 80℃;
General procedure: To a solution of 2-iodobenzamide (3) or 2-bromonicotinamide (6) (2.0 mmol) in DMSO (3 mL), was added aldehyde (2.2 mmol), NaN3 (260 mg, 4.0 mmol), CuBr (29 mg, 0.2 mmol), and l-proline (46 mg, 0.4 mmol). The reaction mixture was stirred at 80 C under air. After disappearance of the reactant (monitored by TLC), water (30 mL) was added to the mixture, and then extracted with ethyl acetate (15 mL) for three times. The extraction was washed with saturated NaCl solution, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using petroleum ether/ethyl acetate (10:1 to 3:1) as the eluent to give the desired products 5 or 7.
With sodium azide; <i>L</i>-proline; copper(I) bromide In dimethyl sulfoxide at 80℃;
4.2. General procedure for preparation of quinazolin-4(3H)-ones (5) and pyrido[2,3-d]pyrimidin-4(3H)-ones (7)
General procedure: To a solution of 2-iodobenzamide (3) or 2-bromonicotinamide (6) (2.0 mmol) in DMSO (3 mL), was added aldehyde (2.2 mmol), NaN3 (260 mg, 4.0 mmol), CuBr (29 mg, 0.2 mmol), and l-proline (46 mg, 0.4 mmol). The reaction mixture was stirred at 80 °C under air. After disappearance of the reactant (monitored by TLC), water (30 mL) was added to the mixture, and then extracted with ethyl acetate (15 mL) for three times. The extraction was washed with saturated NaCl solution, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using petroleum ether/ethyl acetate (10:1 to 3:1) as the eluent to give the desired products 5 or 7.
With sodium azide; <i>L</i>-proline; copper(I) bromide In dimethyl sulfoxide at 80℃;
4.2. General procedure for preparation of quinazolin-4(3H)-ones (5) and pyrido[2,3-d]pyrimidin-4(3H)-ones (7)
General procedure: To a solution of 2-iodobenzamide (3) or 2-bromonicotinamide (6) (2.0 mmol) in DMSO (3 mL), was added aldehyde (2.2 mmol), NaN3 (260 mg, 4.0 mmol), CuBr (29 mg, 0.2 mmol), and l-proline (46 mg, 0.4 mmol). The reaction mixture was stirred at 80 °C under air. After disappearance of the reactant (monitored by TLC), water (30 mL) was added to the mixture, and then extracted with ethyl acetate (15 mL) for three times. The extraction was washed with saturated NaCl solution, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using petroleum ether/ethyl acetate (10:1 to 3:1) as the eluent to give the desired products 5 or 7.
Stage #1: 1-ethyl-2-iodobenzene With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); water In acetonitrile at 80℃; for 8h;
Stage #2: With ammonium hydroxide; iodine In acetonitrile at 60℃; for 12h;
With caesium carbonate In ethylene glycol; dimethyl sulfoxide at 120℃;
Typical procedure for the condensation synthesis of quinazolinones
General procedure: 2-Iodobenzamide 1a (1.0 equiv.), 2-aminoisovaleric acid 2a (3.0 equiv.), Cs2CO3 (3.0 equiv.) and GO/Fe3O4-CuI (Cu+ 0.03 equiv.) were added to DMSO/ethylene glycol (60:1, v/v) in a round bottom flask. The reaction was monitored by TLC. The product was purified by column chromatography with petroleum ether/ethyl acetate (3:1, v/v) to give pure white solid 3a.
With caesium carbonate; In ethylene glycol; dimethyl sulfoxide; at 120℃;
General procedure: 2-Iodobenzamide 1a (1.0 equiv.), 2-aminoisovaleric acid 2a (3.0 equiv.), Cs2CO3 (3.0 equiv.) and GO/Fe3O4-CuI (Cu+ 0.03 equiv.) were added to DMSO/ethylene glycol (60:1, v/v) in a round bottom flask. The reaction was monitored by TLC. The product was purified by column chromatography with petroleum ether/ethyl acetate (3:1, v/v) to give pure white solid 3a.
With caesium carbonate In ethylene glycol; dimethyl sulfoxide at 120℃;
Typical procedure for the condensation synthesis of quinazolinones
General procedure: 2-Iodobenzamide 1a (1.0 equiv.), 2-aminoisovaleric acid 2a (3.0 equiv.), Cs2CO3 (3.0 equiv.) and GO/Fe3O4-CuI (Cu+ 0.03 equiv.) were added to DMSO/ethylene glycol (60:1, v/v) in a round bottom flask. The reaction was monitored by TLC. The product was purified by column chromatography with petroleum ether/ethyl acetate (3:1, v/v) to give pure white solid 3a.
With caesium carbonate In ethylene glycol; dimethyl sulfoxide at 120℃;
Typical procedure for the condensation synthesis of quinazolinones
General procedure: 2-Iodobenzamide 1a (1.0 equiv.), 2-aminoisovaleric acid 2a (3.0 equiv.), Cs2CO3 (3.0 equiv.) and GO/Fe3O4-CuI (Cu+ 0.03 equiv.) were added to DMSO/ethylene glycol (60:1, v/v) in a round bottom flask. The reaction was monitored by TLC. The product was purified by column chromatography with petroleum ether/ethyl acetate (3:1, v/v) to give pure white solid 3a.
N-{(1Z)-3-[(butan-2-yl)amino]-3-oxo-1-phenylprop-1-en-2-yl}-2-iodobenzamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
72%
General procedure: A mixture of the amide (1.29 mmol, 1 equiv), <strong>[156-06-9]phenylpyruvic acid</strong> (323 mg, 1.93 mmol, 1.5 equiv) and pTsOH acid (250 mg, 1.29 mmol, 1 equiv) in anhydrous toluene (the volume required to obtain a concentration of 0.3M respect to the amide) was refluxed under microwave heating (150 watts, 60 min) using a Dean-Stark trap. Then, the reaction was cooled to 0 oC in an ice-water bath and triethylamine (0.3 mL, 1.94 mmol, 1.5 equiv) and sec-butylamine (0.4 mL, 2.58 mmol, 2 equiv) were added sequentially via syringe and the stirring continued for two hours at room temperature. The mixture reaction cooled down to 0 oC, followed by the dropwise addition of POCl3 (0.61 mL, 6.45 mmol, 5 equiv). The resultant mixture was refluxed (90 watts, 20 min), cooled down to 0 oC and quenched with saturated aqueous NaHCO3 (pH = 9). The two phases were separated and the aqueous layer was extracted with EtOAc (5 mL x 5). The organic extracts were combined, washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to provide a viscous oil. The crude product was subjected to purification by flash column chromatography on silica gel (98:02 hexanes/EtOAc) to afford the desired product.
Stage #1: 4-methoxycinnamaldehyde With palladium 10% on activated carbon; sodium carbonate In isopropyl alcohol at 120℃; for 6h; Inert atmosphere;
Stage #2: With iodobenzene; tetra-(n-butyl)ammonium iodide In 1-methyl-pyrrolidin-2-one at 120℃; for 18h; Inert atmosphere;
Stage #3: o-iodobenzamide With palladium 10% on activated carbon; sodium carbonate In 1-methyl-pyrrolidin-2-one at 120℃; for 24h; Inert atmosphere;
10.45 Systems that react simultaneously in multiple containers:
General procedure: In the following reaction formulas, the reaction vessel shown in FIG. 1 was used and the yields were examined and listed in Table 10.The amount of the substrate of tube 1 (Tube 1) to the substrate of tube 2 (Tube 2) is 1.5 equivalents.The pipe 1 and the pipe 2 are connected, and the carbon monoxide generated in the pipe 1 comes and goes in the connecting portion, and the pipe 2 can also use carbon monoxide.
With ammonium hydroxide; palladium dichloride at 90℃; for 0.166667h; Microwave irradiation; Green chemistry;
1 Example 1: Preparation of quinazoline-4(3H)-one:
(1) Adding 0.2 mmol of palladium chloride and 1 mmol of 2-iodobenzamide to the microwave reaction tube. 1.2 mmol of hydrogen cyanide 2 ml of ammonia water, then reacted at 120 w, 90 ° C for 10 minutes. The product was extracted with ethyl acetate and concentrated under reduced pressure, The product was purified by column chromatography to give a white solid. The yield was 96%. (2) The 2-iodobenzamide in (1) was replaced with 2-bromobenzamide in a yield of 94%.
With potassium tert-butylate; In water; for 6h;pH 13.0;Inert atmosphere; Irradiation;
General procedure: The following procedure is representative of all the photoinduced reactions. The reactions were carried out in a 50-mL three-neck round-bottomed flask equipped with a nitrogen inlet and magnetic stirrer. To 5 mL of degassed water (using a water vacuum pump), potassium t-butoxide (44.6 mg, 0.398 mmol) or KOH (33.4 mg, 0.596 mmol) was added. After total dissolution of the base, 2-naphthol (42.9 mg, 0.298 mmol) was added and the mixture stirred for 5 min, and then 4 (28.2 mg, 0.108 mmol) was added. The reaction mixture was irradiated for 360 min. Irradiation was conducted in a reactor equipped with two Philips HPI-T 400-W lamps (lambda ? 350 nm, cooled with water) or with an LED lamp (LED Lustrous Colour Xnes lamp, lambda= 400 ± 20 nm, 9.4 V, 1050 mA) (see Reactors section in the Supplementary Material). After that, the reaction was stopped by adding an excess of ammonium nitrate and 10 mL of water. The crude was then extracted with ethyl acetate; the organic layer was dried over Na2SO4, filtered, and vacuum-concentrated. Products were isolated using column chromatography (pentane/acetone 80/20). The halide ion concentration in the aqueous solution was determined by potentiometric titration. Dark reactions were carried out by covering the vessel with aluminium foil before degasification.
With diphenyl phosphoryl azide; triethylamine In toluene at 110℃; Sealed tube;
Ureas, Acylureas, Carbamates, and Thiocarbamates; General Procedure
General procedure: N-Acylbenzotriazole 1 (1.0 equiv.) and diphenylphosphoryl azide (DPPA, 1.1 equiv.) in anhydrous toluene (3 mL) was taken into a sealed tube, and shaken for 5 min. Then, the required nucleophile (e.g., amine, benzamide, phenol, or thiol; 1.0 equiv.) was added, followed by addition of Et3N (2.0 equiv.) as base. Further, the resulting reaction mixture was stirred for 3-4 h at 110 °C in a sealed tube. After completion of the reaction (monitored by TLC), the reaction mixture was concentrated under reduced pressure and subjected to column chromatography (n-hexane/EtOAc) to afford the corresponding urea, N-acylurea, carbamate, or thiocarbamate as the desired product.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
