* 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 sodium ethanolate In ethanol at 20℃; for 1 h;
General procedure: A mixture of a solution of sodium ethoxide (0.1 mmol) in ethanol (3 mL), ethyl cyanoacetate (10 mmol) and amine (10 mmol) was stirred at room temperature. The reaction time is 1 h for primary amines and 24 h for secondary amine 2d. The precipitate obtained was separated by filtration, washed with diethylether and recrystallised in ethanol to provide a white solid of cyanoacetamides.
75%
at 20 - 25℃; for 24 h;
General procedure: A mixture of ethyl cyanoacetate (1.1g, 10mmol) and amine (11mmol) was stirred at 20-25°C. After 24 h, the Precipitate will be filtered and washed with cold diethyl ether, then dried on vacuum.
68%
for 4 h; Heating / reflux
EXAMPLE 1; General Methodfor Synthesis of Compounds; N- (Phenylalkyl) cinnamides were prepared by the following general procedure. Benzylamine (3. 0g, 28 mmol) and ethyl cyanoacetate (4. 7 g, 42 mmol) in acetonitrile (20 mL) was stirred and reflux for 4 hr. Benzylamine in this general procedure can be replaced by any other substituents depicted as R3 above. The solvent was removed in vacuo to give an oil which solidified upon standing. Precipitation (EtOAc) resulted in 3.28g (68percent) of an off-white powder corresponding to N-benzylcyanoacetamide as an intermediate. A mixture of N- benzylcyanomethylamide (1.3, 7.5 mmol), 3,4-dihydroxybenzaldehyde (1.1 g, 8.2 mmol), and piperidine (catalytic, 5 drops) was stirred at reflux for 3 hr. Flash chromatography (EtOAc) followed by two recrystalizations (H20/EtOH) yielded product as a white powder 0.8g (36percent).
Reference：
[1] Organic Letters, 2009, vol. 11, # 9, p. 2003 - 2006
[2] Chemical Communications, 2017, vol. 53, # 12, p. 2020 - 2023
[3] Organic Letters, 2014, vol. 16, # 7, p. 2018 - 2021
[4] Tetrahedron, 2011, vol. 67, # 8, p. 1540 - 1551
[5] Angewandte Chemie - International Edition, 2015, vol. 54, # 9, p. 2849 - 2853[6] Angew. Chem., 2015, vol. 127, # 9, p. 2891 - 2896,6
[7] European Journal of Medicinal Chemistry, 2013, vol. 59, p. 141 - 149
[8] Patent: WO2005/58829, 2005, A1, . Location in patent: Page/Page column 22
[9] Journal of Medicinal Chemistry, 1999, vol. 42, # 17, p. 3412 - 3420
[10] Chem. Zentralbl., 1901, vol. 72, # I, p. 578
[11] Atti R. Acad. Scienze Torino, vol. 27, p. 222[12] Chemische Berichte, 25 Ref. <1892>, 326,
[13] Journal of the Indian Chemical Society, 1978, vol. 55, # 3, p. 281 - 283
[14] Synthetic Communications, 1990, vol. 20, # 20, p. 3235 - 3243
[15] Journal of Agricultural and Food Chemistry, 2008, vol. 56, # 13, p. 5242 - 5246
[16] Journal of Agricultural and Food Chemistry, 2010, vol. 58, # 5, p. 2730 - 2735
[17] Ultrasonics Sonochemistry, 2010, vol. 17, # 5, p. 909 - 915
[18] Journal of the Korean Chemical Society, 2012, vol. 56, # 4, p. 459 - 463
[19] European Journal of Medicinal Chemistry, 2016, vol. 107, p. 219 - 232
[20] Chemical Biology and Drug Design, 2016, p. 43 - 53
[21] Molecular Pharmaceutics, 2018, vol. 15, # 6, p. 2206 - 2223
[22] Patent: WO2009/124013, 2009, A1, . Location in patent: Page/Page column 21-22
2
[ 372-09-8 ]
[ 100-46-9 ]
[ 10412-93-8 ]
Yield
Reaction Conditions
Operation in experiment
14%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;
To stirred solution of diisopropylethyl amine (506 μl, 3 mmol) and benzylamine (327 μl, 3 mmol) in DMF was added cyanoacetic acid (85 mg, 1 mmol), EDC (625 mg, 3 mmol), and HOBt (208 mg, 1.5 mmol). The reaction was stirred room temperature overnight. The reaction was then diluted with ether and the organic layer was washed twice with 1N HCl and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated by rotary evaporation. The clear residue was lyophilized from benzene to give 24 mg (14percent yield) of an off-white powder that needed no further purification.
Reference：
[1] Patent: US2013/35325, 2013, A1, . Location in patent: Paragraph 0302; 0303
[2] Organic and Biomolecular Chemistry, 2015, vol. 13, # 27, p. 7487 - 7499
[3] Organic and Biomolecular Chemistry, 2015, vol. 13, # 27, p. 7487 - 7499
3
[ 100-46-9 ]
[ 105-34-0 ]
[ 10412-93-8 ]
Reference：
[1] Journal of Medicinal Chemistry, 2014, vol. 57, # 18, p. 7590 - 7599
[2] Organic Letters, 2011, vol. 13, # 11, p. 2884 - 2887
[3] Patent: US5652250, 1997, A,
[4] Journal of Medicinal Chemistry, 1991, vol. 34, # 6, p. 1896 - 1907
[5] Bioorganic and Medicinal Chemistry, 1999, vol. 7, # 8, p. 1727 - 1736
[6] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 11, p. 3019 - 3026
[7] Chemistry - A European Journal, 2015, vol. 21, # 42, p. 14851 - 14861
Reference：
[1] Chem. Zentralbl., 1901, vol. 72, # I, p. 578
6
[ 5459-58-5 ]
[ 100-46-9 ]
[ 10412-93-8 ]
[ 71-36-3 ]
Reference：
[1] Journal of Physical Organic Chemistry, 1999, vol. 12, # 10, p. 747 - 750
7
[ 10412-93-8 ]
[ 139-85-5 ]
[ 133550-30-8 ]
Yield
Reaction Conditions
Operation in experiment
36%
for 3 h; Heating / reflux
EXAMPLE 1; General Methodfor Synthesis of Compounds; N- (Phenylalkyl) cinnamides were prepared by the following general procedure. Benzylamine (3. 0g, 28 mmol) and ethyl cyanoacetate (4. 7 g, 42 mmol) in acetonitrile (20 mL) was stirred and reflux for 4 hr. Benzylamine in this general procedure can be replaced by any other substituents depicted as R3 above. The solvent was removed in vacuo to give an oil which solidified upon standing. Precipitation (EtOAc) resulted in 3.28g (68percent) of an off-white powder corresponding to N-benzylcyanoacetamide as an intermediate. A mixture of N- benzylcyanomethylamide (1.3, 7.5 mmol), 3,4-dihydroxybenzaldehyde (1.1 g, 8.2 mmol), and piperidine (catalytic, 5 drops) was stirred at reflux for 3 hr. Flash chromatography (EtOAc) followed by two recrystalizations (H20/EtOH) yielded product as a white powder 0.8g (36percent).
Reference：
[1] Journal of Medicinal Chemistry, 1991, vol. 34, # 6, p. 1896 - 1907
[2] Journal of Medicinal Chemistry, 1999, vol. 42, # 17, p. 3412 - 3420
[3] Patent: WO2005/58829, 2005, A1, . Location in patent: Page/Page column 22
With sodium ethanolate; In ethanol; at 20℃; for 1h;
General procedure: A mixture of a solution of sodium ethoxide (0.1 mmol) in ethanol (3 mL), ethyl cyanoacetate (10 mmol) and amine (10 mmol) was stirred at room temperature. The reaction time is 1 h for primary amines and 24 h for secondary amine 2d. The precipitate obtained was separated by filtration, washed with diethylether and recrystallised in ethanol to provide a white solid of cyanoacetamides.
80%
In ethanol; at 20℃;
General procedure: In a simply obtainable screw cap bottle, a mixture of ethylcyanoacetate6 (1.2 mmol) and the suitable amine (1 mmol) in EtOH (10 mL)was stirred at RT for 4-8 h. After completion as indicated by TLC, thereaction liquid was refrigerated down to 4 C in an ice bath. In severalcases, the precipitation of amide usually took later than some minutesto hours [12]. Filtered off the formed solid, rinsed with ether numeroustimes to obtain pure 7(a-q) in corresponding yield.
75%
at 20 - 25℃; for 24h;
General procedure: A mixture of ethyl cyanoacetate (1.1g, 10mmol) and amine (11mmol) was stirred at 20-25C. After 24 h, the Precipitate will be filtered and washed with cold diethyl ether, then dried on vacuum.
68%
In acetonitrile; for 4h;Heating / reflux;
EXAMPLE 1; General Methodfor Synthesis of Compounds; N- (Phenylalkyl) cinnamides were prepared by the following general procedure. Benzylamine (3. 0g, 28 mmol) and ethyl cyanoacetate (4. 7 g, 42 mmol) in acetonitrile (20 mL) was stirred and reflux for 4 hr. Benzylamine in this general procedure can be replaced by any other substituents depicted as R3 above. The solvent was removed in vacuo to give an oil which solidified upon standing. Precipitation (EtOAc) resulted in 3.28g (68%) of an off-white powder corresponding to N-benzylcyanoacetamide as an intermediate. A mixture of N- benzylcyanomethylamide (1.3, 7.5 mmol), 3,4-dihydroxybenzaldehyde (1.1 g, 8.2 mmol), and piperidine (catalytic, 5 drops) was stirred at reflux for 3 hr. Flash chromatography (EtOAc) followed by two recrystalizations (H20/EtOH) yielded product as a white powder 0.8g (36%).
In ethanol;Reflux;
General procedure: To a solution of different amines (1 mmol) in ethanol (10 mL), ethylcyanoacetate (1.2 mmol) was added. The reaction mixture was stirred for 5-8 h under reflux. Progress of the reaction was monitoredby TLC. After completion of the reaction, the resulting mixture was cooled to 0-5 C in an ice bath and the solid separated was filtered off.
at 20℃; for 24.25h;
[0082] General procedure for synthesis of 3. Ethyl cyanoacetate (11.31 g, 0.1 mol) was added dropwise to the respective amine (0.25 mol) within 15 min, and stirring was continued at room temperature (24 h) to give cynoacetic acid amide. beta-Keto acetic acid esters (0.1 mol) and piperidine (10 mL) were added, and the mixture was stirred at 100 C (20 h). The solvent was evaporated, and the pH was adjusted to 1 with 32% aqueous HCl. After precipitation at room temperature, the product was filtered off and washed with water and ether to give a material of sufficient purity (>90%) for further reaction.
EXAMPLE 7 N-benzyl alpha-cyanoacetamide To benzylamine (1.07 g, 0.01 mol) was added methyl cyanoacetate (0.99 g, 0.01 mol) and the mixture was heated for 16 h at 100 C. without condenser to allow evaporation of the methanol formed. Cooling gave a dark red solid which was triturated with ethanol, filtered and recrystallized from ethanol to give pure title compound in about 40% yield (0.70 g). mp 123-4 C. MS m/z 174.
1
EXAMPLE 1; General Methodfor Synthesis of Compounds; N- (Phenylalkyl) cinnamides were prepared by the following general procedure. Benzylamine (3. 0g, 28 mmol) and ethyl cyanoacetate (4. 7 g, 42 mmol) in acetonitrile (20 mL) was stirred and reflux for 4 hr. Benzylamine in this general procedure can be replaced by any other substituents depicted as R3 above. The solvent was removed in vacuo to give an oil which solidified upon standing. Precipitation (EtOAc) resulted in 3.28g (68%) of an off-white powder corresponding to N-benzylcyanoacetamide as an intermediate. A mixture of N- benzylcyanomethylamide (1.3, 7.5 mmol), 3,4-dihydroxybenzaldehyde (1.1 g, 8.2 mmol), and piperidine (catalytic, 5 drops) was stirred at reflux for 3 hr. Flash chromatography (EtOAc) followed by two recrystalizations (H20/EtOH) yielded product as a white powder 0.8g (36%).
With 1-methyl-piperazine; In ethanol; at 20 - 25℃;
General procedure: A mixture of aromatic aldehydes (2 mmol) along with 2-cyanoacetamide (4) (168 mg, 2 mmol) and N-methylpiperazine (40 mg, 0.4mmol) was stirred in EtOH(10 mL) and allowed to stand at 20-25C. After the reaction was complete (monitored by thin-layer chromatography, TLC), the product was diluted with ethyl acetate (10 mL).The solvent layer was washed three times successively with sodium metabisulphite solution (20%, g/g) and brine and dried over anhydrous sodium sulphate. After removal of the solvent, the product was purified by direct recrystallization from EtOH/petroleum ether.
With piperidine; In ethanol; at 20℃; for 1h;Product distribution / selectivity;
To 3, 4-dihydroxycinnamaldehyde A12 (example 59) (32 mg, 0.2 mmol) and amide A3 (Example 4) (32 mg, 0.2 mmol) in 8 mL of ethanol 40 gl of piperidine was added and the mixture was kept at room temperature for 1 h. 2N HCI and water were added and the precipitated solid was recrystallized from ethanol-water to give 44 mg (68%) of an orange solid. The analytical data were identical to the compound prepared as described in Example 8.
56%
Cinnamaldehyde E (11.0 g ; corrected with the HPLC purity) was dissolved in methanol (500 g). The solution was filtered over a nutsch, which is rinsed with methanol (80 g). At 20-25 C, intermediate F (8.5 g) was added in one portion to the methanol solution followed by the addition of piperidine (9.1 g) in several portions. The deep red solution was stirred for at least 3 hours and an in-process control performed. Upon total conversion of starting material, 370 g of methanol was distilled off at 40-45 C. To the resulting residue was added 16.6 g OF HCL (32%) and water (150 g). The color changed from red to yellow and the product precipitated out of solution provided that pH was between 1 and 1.3. The suspension was then cooled to 0-5 C and stirred for at least 2-3 hours (up to 20 hours) to maximize the yield. The suspension was then filtered via a nutsch and the residue rinsed with water (25 g) to yield 15.1 g of G. The wet G (15 g) was then suspended in acetonitrile (600 g) and heated to 80-82 C for 1 h. The suspension was then cooled to 0-5 C and stirred for at least 3 h. The wet material was separated with a nutsch and rinsed twice with a mixture of ethanol (10 g) and water (20 g). Final drying in the vacuum dryer at 45 C yields 10.2 g of yellowish G in an overall yield of 56% (over two steps).
EXAMPLE 6 Synthesis of Cyanoester G Cinnamaldehyde E (11.0 g; corrected with the HPLC purity) was dissolved in methanol (500 g). The solution was filtered over a nutsch, which is rinsed with methanol (80 g). At 20-25 C., intermediate F (8.5 g) was added in one portion to the methanolic solution followed by the addition of piperidine (9.1 g) in several portions. The deep red solution was stirred for at least 3 hours and an in-process control performed. Upon total conversion of starting material, 370 g of methanol was distilled off at 4045 C. To the resulting residue was added 16.6 g of HCl (32%) and water (150 g). The color changed from red to yellow and the product precipitated out of solution provided that pH was between 1 and 1.3. The suspension was then cooled to 0-5 C. and stirred for at least 2-3 hours (up to 20 hours) to maximize the yield. The suspension was then filtered via a nutsch and the residue rinsed with water (25 g) to yield 15.1 g of G. The wet G (15 g) was then suspended in acetonitrile (600 g) and heated to 80-82 C. for 1 h. The suspension was then cooled to 0-5 C. and stirred for at least 3 h. The wet material was separated with a nutsch and rinsed twice with a mixture of ethanol (10 g) and water (20 g). Final drying in the vacuum dryer at 45 C. yields 10.2 g of yellowish G in an overall yield of 56% (over two steps).
5.6. Synthesis Of (E)-2-(benzylaminocarbonyl)-3-(3-iodo-4,5-dihydroxyphenyl)acrylonitrile A preferred method of synthesis of (E)-2-(benzylaminocarbonyl)-3-(3-iodo-4,5-dihydroxyphenyl)acrylonitrile (Compound 6) is as follows: A mixture of 0.4 g of 2-cyano-3-(4-hydroxy-3-iodo-5-methoxy)phenylacrylonitrile (which was prepared by condensation of 4-hydroxy-3-iodo-5-methoxybenzaldehyde with N-benzylcyanoacetamide) and 0.5 ml of BBr3 in 20 ml dichloromethane was stirred for 2 hours at room temperature. Workup (H2 O, ethyl acetate) gave 0.16 g of a yellow solid (41% yield) having a melting point of 220 C. The product gave the following analytical data: NMR (acetone-d6) delta 8.05 (1H, S, vinyl), 7.85 (1H, d, J=2.1 Hz), 7.70 (1H, d, J=2.1 Hz), 7.30 (5H, m), 4.6 (2H, S).
41%
With boron tribromide; In dichloromethane;
5.6. Synthesis Of (E)-2-(benzylaminocarbonyl)-3-(3-iodo-4,5-dihydroxyphenyl)acrylonitrile A preferred method of synthesis of (E)-2-(benzylaminocarbonyl)-3-(3-iodo-4,5-dihydroxyphenyl)acrylonitrile (Compound 6) is as follows: A mixture of 0.4 g of 2-cyano-3-(4-hydroxy-3-iodo-5-methoxy)phenylacrylonitrile (which was prepared by condensation of 4-hydroxy-3-iodo-5-methoxybenzaldehyde with N-benzylcyanoacetamide) and 0.5 ml of BBr3 in 20 ml dichloromethane was stirred for 2 hours at room temperature. Workup (H2 O, ethyl acetate) gave 0.16 g of a yellow solid (41% yield) having a melting point of 220 C. The product gave the following analytical data: NMR (acetone-d6) delta 8.05(1H,S,vinyl), 7.85(1H,d,J=2.1 Hz), 7.70(1H,d,J=2.1 Hz), 7.30(5H,m), 4.6(2H,S).
With boron tribromide; In dichloromethane;
5.6. Synthesis Of (E)-2-(benzylaminocarbonyl)-3-(3-iodo-4,5-dihydroxyphenyl)acrylonitrile A preferred method of synthesis of (E)-2-(benzylaminocarbonyl)-3-(3-iodo-4,5-dihydroxyphenyl)acrylonitrile (Compound 6) is as follows: A mixture of 0.4 g of 2-cyano-3-(4-hydroxy-3-iodo-5-methoxy)phenylacrylonitrile (which was prepared by condensation of 4-hydroxy-3-iodo-5-methoxybenzaldehyde with N-benzylcyanoacetamide) and 0.5 ml of BBr3 in 20 ml dichloromethane was stirred for 2 hours at room temperature. Workup (H2 O, ethyl acetate) gave 0.16 g of a yellow solid (41 yield) having a melting point of 220 C. The product gave the following analytical data: NMR (acetone-d6) delta 8.05(1H,S,vinyl), 7.85(1H,d,J=2.1 Hz), 7.70(1H,d,J=2.1 Hz), 7.30(5H,in), 4.6(2H,S).
(2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-benzyl-2-cyanopenta-2,4-dienamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
71%
2.0 g (11.13 MMOL) of the product from Example 2 (3,4- methylenedioxycinnamaldehyde), 76.8 g of ethanol (absolute) and 0.1093 g of piperidine were initially introduced into a 250 mL three-necked round-bottomed flask. The suspension was stirred at room temperature for 1 hour to dissolve the crystals. Then, 2.26 g of (cyanoacetyl) benzamide were added to the reaction mixture. This solution was stirred for 6-8 hours, during which a suspension was formed. After 6-8 hours, the suspension was filtered off and the residue (3.4 g of yellow, moist crystals) was washed with a small amount of absolute ethanol. This residue was dried overnight in a drying cabinet at 40 C and about 20 mbar. Drying gave 2.7 g of (E, E)-2- (benzylamido)-3- (3, 4-methylenedioxystyryl) acrylonitrile (yield: 71%) as yellow crystals. The identity and purity were confirmed by means of 1H NMR AND HPLC.
71%
EXAMPLE 3 Reaction of 3,4-methylenedioxycinnamaldehyde with 2-benzylamidoacrylonitrile, Knoevenagel Reaction 2.0 g (11.13 mmol) of the product from Example 2 (3,4-methylenedioxycinnamaldehyde), 76.8 g of ethanol (absolute) and 0.1093 g of piperidine were initially introduced into a 250 mL three-necked round-bottomed flask. The suspension was stirred at room temperature for 1 hour to dissolve the crystals. Then, 2.26 g of (cyanoacetyl)benzamide were added to the reaction mixture. This solution was stirred for 6-8 hours, during which a suspension was formed. After 6-8 hours, the suspension was filtered off and the residue (3.4 g of yellow, moist crystals) was washed with a small amount of absolute ethanol. This residue was dried overnight in a drying cabinet at 40 C. and about 20 mbar. Drying gave 2.7 g of (E,E)-2-(benzylamido)-3-(3,4-methylenedioxystyryl)acrylonitrile (yield: 71%) as yellow crystals. The identity and purity were confirmed by means of 1H NMR and HPLC.
N-benzyl-2,5-dihydro-2-imino-4,5,5-trimethylfuran-3-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
94%
General procedure: A mixture of 3-hydroxy-3-methylbutan-2-one 1 (10 mmol) and the substituted cyanoacetamides 2a-d (10 mmol) with a solution of sodium ethoxide (0.5 mmol) in ethanol (10 mL) was stirred at room temperature. After evaporation of the solvent, the residue was acidified with 6 M aqueous HCl. The mixture was neutralised with a solution of potassium carbonate (10%), then extracted with CH2Cl2 (3×25 mL). The combined organic layers were dried on MgSO4, filtered and concentrated in vacuum. The recovered solid was recrystallised in ethanol to provide compounds 3a-d.
With 42H3N*42H(1+)*72Mo(6+)*60Mo(5+)*372O(2-)*72H2O*30C2H3O2(1-); In neat (no solvent); at 110℃; for 0.2h;Green chemistry;Catalytic behavior;
General procedure: A mixture of a salicylaldehyde (1a or 1b, 1 mmol), N-alkyl-2-cyanoacetamides (2a-2f,1 mmol), and {Mo132} (0.05 g) was heated in an oil bath at 110 C for 5-15 min. Aftercompletion of the reaction, monitored by TLC on silica gel (n-hexane-ethyl acetate,3:2), the mixture was cooled to room temperature and hot ethanol (10 ml) was added.The catalyst was collected by filtration and washed with a small portion of hot ethanol(5 ml). The combined filtrate was concentrated by half and allowed to stand at roomtemperature. The precipitated solid was collected by filtration, and recrystallized from96% ethanol to give compounds 3a-3i in high yields (see Table 2).
General procedure: To a stirred solution of cyanamide (2, 1.1 mmol) in ethanol (2 mL) were added 2-hydroxybenzaldehyde (1 mmol) and piperidine(catalytic amount), and the resulting mixture was stirred at room temperature for 12 h. The suspension was then filtered to give 4, which was used directly in the next step.
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;
To stirred solution of diisopropylethyl amine (506 mul, 3 mmol) and benzylamine (327 mul, 3 mmol) in DMF was added cyanoacetic acid (85 mg, 1 mmol), EDC (625 mg, 3 mmol), and HOBt (208 mg, 1.5 mmol). The reaction was stirred room temperature overnight. The reaction was then diluted with ether and the organic layer was washed twice with 1N HCl and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated by rotary evaporation. The clear residue was lyophilized from benzene to give 24 mg (14% yield) of an off-white powder that needed no further purification.
With pyridine; titanium tetrachloride; In tetrahydrofuran; at 0 - 20℃;
General procedure: A mixture of <strong>[1889-71-0]1-(4-chlorophenyl)-2-phenylethanone</strong> (2, 1.1 mmol) and 2-cyanoacetamide (2.2 mmol) in THF (10 mL) was slowly added to a solution of TiCl4 (5.5 mmol) in dry THF (20 mL) at 0 C. After removing the ice bath, pyridine (0.2 mL) was added. And the reaction mixture was stirred at room temperature overnight. The progress of the reaction was monitored by TLC. After completion of the reaction, THF was removed under reduced pressure and the residue was dissolved in ethyl acetate (30 mL), washed with water (2 × 30 mL) and brine (2 × 30 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude olefin intermediate (3) was used for the next step without purification.
General procedure: (E)--aryl--cyanoacrylamides 2 was prepared according to literature procedure.2 General procedure for 2a. To a solution of benzaldehyde (10 mmol 1.0 equiv), pyrrolidine (2 mmol, 20 mol %) in ethanol (20 mL) was added N-benzyl-2-cyanoacetamide (10 mmol, 1.0 equiv). The reaction mixture was stirred at room temperature until the reaction was complete (monitored by TLC), the solvent was removed under reduced pressure. The crude reaction mixture was purified through flash column chromatography on silica gel to afford 2a. 1H NMR (CDCl3, 400 MHz): delta (ppm) 8.68 (s, 1H), 7.78-7.74 (m, 1H), 7.70 (dd, J = 7.6, 1.4 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz): delta (ppm) 167.9, 154.4, 137.8, 131.0, 126.4, 118.8, 115.6.
(E)-N-benzyl-2-cyano-3-(4-bromophenyl)acrylamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With pyrrolidine; In ethanol; at 20℃;
General procedure: (E)--aryl--cyanoacrylamides 2 was prepared according to literature procedure.2 General procedure for 2a. To a solution of benzaldehyde (10 mmol 1.0 equiv), pyrrolidine (2 mmol, 20 mol %) in ethanol (20 mL) was added N-benzyl-2-cyanoacetamide (10 mmol, 1.0 equiv). The reaction mixture was stirred at room temperature until the reaction was complete (monitored by TLC), the solvent was removed under reduced pressure. The crude reaction mixture was purified through flash column chromatography on silica gel to afford 2a.
(E)-N-benzyl-3-(4-chlorophenyl)-2-cyanoacrylamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With pyrrolidine; In ethanol; at 20℃;
General procedure: (E)--aryl--cyanoacrylamides 2 was prepared according to literature procedure.2 General procedure for 2a. To a solution of benzaldehyde (10 mmol 1.0 equiv), pyrrolidine (2 mmol, 20 mol %) in ethanol (20 mL) was added N-benzyl-2-cyanoacetamide (10 mmol, 1.0 equiv). The reaction mixture was stirred at room temperature until the reaction was complete (monitored by TLC), the solvent was removed under reduced pressure. The crude reaction mixture was purified through flash column chromatography on silica gel to afford 2a.
General procedure: (E)--aryl--cyanoacrylamides 2 was prepared according to literature procedure.2 General procedure for 2a. To a solution of benzaldehyde (10 mmol 1.0 equiv), pyrrolidine (2 mmol, 20 mol %) in ethanol (20 mL) was added N-benzyl-2-cyanoacetamide (10 mmol, 1.0 equiv). The reaction mixture was stirred at room temperature until the reaction was complete (monitored by TLC), the solvent was removed under reduced pressure. The crude reaction mixture was purified through flash column chromatography on silica gel to afford 2a.
General procedure: (E)--aryl--cyanoacrylamides 2 was prepared according to literature procedure.2 General procedure for 2a. To a solution of benzaldehyde (10 mmol 1.0 equiv), pyrrolidine (2 mmol, 20 mol %) in ethanol (20 mL) was added N-benzyl-2-cyanoacetamide (10 mmol, 1.0 equiv). The reaction mixture was stirred at room temperature until the reaction was complete (monitored by TLC), the solvent was removed under reduced pressure. The crude reaction mixture was purified through flash column chromatography on silica gel to afford 2a.
General procedure: (E)--aryl--cyanoacrylamides 2 was prepared according to literature procedure.2 General procedure for 2a. To a solution of benzaldehyde (10 mmol 1.0 equiv), pyrrolidine (2 mmol, 20 mol %) in ethanol (20 mL) was added N-benzyl-2-cyanoacetamide (10 mmol, 1.0 equiv). The reaction mixture was stirred at room temperature until the reaction was complete (monitored by TLC), the solvent was removed under reduced pressure. The crude reaction mixture was purified through flash column chromatography on silica gel to afford 2a.
To a solution of N-benzyl-2-cyanoacetamide (1.74 g, 0.01 mol) in ethanol (20 mL) was added piperidine and 3, 4-di hydroxyl-5-nitrobenzaldehyde (1.83 g, 0.01 mol). The reaction mass was heated to 70-75 C for 2-3 hours. After completion of the reaction, the solid that formed was filtered off. To the solid was added demineralized water and the mixture was neutralized using diluted HCl. The residue was filtered off to afford the pure compound, which had a melting point of 200.9 - 204.1 C.
2-amino-N-benzyl-7-methyl-5-oxo-5H-chromeno[2,3-b]pyridine-3-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
57%
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In ethanol; for 0.5h;Reflux;
A. A mixture of nitrile 1 (0.55 g, 3.0 mmol) and N-benzyl-2-cyanoacetamide (0.52 g, 3.0 mmol) in abs. EtOH (20 ml) containing DBU (0.1 ml, 0.7 mmol) was refluxed for 30 min. The white crystals obtained during heating were filtered off and recrystallized from DMF-EtOH. Yield 0.63 g (57%).
N-benzyl-8-imino-4-methyl-2-oxo-2H,8H-pyrano[2,3-f]chromene-9-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With triethylamine; In ethanol; at 50℃;
General procedure: To a solution of 5 (1.5 mmol) and 2a-s (3.1 mmol) in ethanol (10 mL) was added Et3N (0.1 mmol) dropwise at room temperature. The resulting mixture was stirred at 50 C for 2-3 h and then allowed to cool to room temperature. The product was precipitated from the reaction mixture, collected by filtration and washed with methanol (2-3 mL) to yield corresponding final products (6a-s).
With sodium azide; triethylamine hydrochloride; In toluene; at 90℃; for 20h;
General procedure: To a stirred solution of N-alkyl-substituted 2-cyanoacetamide 1 (5mmol) in toluene (10 mL) was added NaN3 (3 equiv) and triethylamine hydrochloride salt (3 equiv). The reaction mixture was heated to 90 C for 20 h. Ice-cold H2O (25 mL) was added to the reaction mixture and acidified with aq HCl and stirred at 0 C for 30 min. The precipitated product was collected by filtration, washed with cold H2O(25 mL), and dried in vacuum (Table 1).
The ketolide 3 (0.20 g, 0.3 mmol) was dissolved in THF (15 mL)and the solution cooled to 0 C before NaH (60%, 0.02 g) was added.N-Benzyl-2-cyanoacetamide (0.13 g, 0.76 mmol) was added to thereaction mixture which was stirred at room temperature for 17 h.The mixture was cooled to 0 C, quenched with NaHCO3 andextracted with ethyl acetate, the extracts washed with brine anddried (MgSO4). The solution was evaporated and the residual materialwas subjected to flash chromatography on silica gel using CH2-Cl2:MeOH:NH3(aq) 90:5:1. The product 23 was a white solid; yield0.16 g (63%). The product 19 (0.09 g) was stirred in methanol (2 mL) for 14 h.The solvent was evaporated, and the product was subjected to flashchromatography on silica gel using CH2Cl2:MeOH:NH3(aq) 90:5:1.The product 20
N-benzyl-5-oxo-5,10-dihydro-4H-benzo[e][1,2,3]triazolo[1,5-b][2,4]diazepine-3-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
67%
General procedure: To a solution of 0.87 g t-BuOK (7.8 mmol) in 10 cm3 drymethanol, 2-cyanoacetamide 2a-2g (2.9 mmol) was added.The reaction mixture was stirred for 10-15 min, followed by cooling to 0 C and adding a solution of o-(azidomethyl)benzoate 1a-1c (2.6 mmol) in 5 cm3 drymethanol. After heating the reaction mixture back to room temperature, it was stirred under TLC monitoring for36-48 h and evaporated. Water (15 cm3) was added to the residue and it was acidified with HCl to pH 4-5. The resulting precipitate was filtered off and recrystallized from acetic acid.
N-benzyl-7-bromo-5-oxo-5,10-dihydro-4H-benzo[e][1,2,3]triazolo[1,5-ba][2,4]diazepine-3-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
61%
General procedure: To a solution of 0.87 g t-BuOK (7.8 mmol) in 10 cm3 drymethanol, 2-cyanoacetamide 2a-2g (2.9 mmol) was added.The reaction mixture was stirred for 10-15 min, followed by cooling to 0 C and adding a solution of o-(azidomethyl)benzoate 1a-1c (2.6 mmol) in 5 cm3 drymethanol. After heating the reaction mixture back to room temperature, it was stirred under TLC monitoring for36-48 h and evaporated. Water (15 cm3) was added to the residue and it was acidified with HCl to pH 4-5. The resulting precipitate was filtered off and recrystallized from acetic acid.
methyl 2-(azidomethyl)furan-3-carboxylate[ No CAS ]
N-benzyl-5-oxo-5,9-dihydro-4H-furo[3,2-e]-[1,2,3]triazolo[1,5-a][1,3]diazepine-3-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
54%
With potassium tert-butylate; In methanol; at 0 - 20℃; for 48h;
General procedure: 2-Cyanoacetamide 2a-2d, 33 mmol, was added to a solution of 0.5 g (28 mmol) of 2-(azidomethyl)furan-3-carboxylate (1) in 8 mL of anhydrous methanol, the mixture was cooled to 0C, and a solution of 0.63 g (56 mmol) of potassium tert-butoxide in 10 mL of methanol was added in portions. The mixture was stirred for 48 h at room temperature, the solid precipitate was filtered off and dissolved in 10 mL of water, the solution was acidified with aqueous HCl to pH 5, and the precipitatewas filtered off and recrystallized from acetic acid.
(2Z)-N-benzyl-2-(4-oxo-1,3-thiazolidin-2-ylidene)acetamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
61%
With dmap; In pyridine; for 12h;Reflux;
General procedure: Pyridine was added dropwise with stirring to cyanoacetamide 2a-e(15 mmol) in a round-bottom flask until complete dissolution of the cyanoacetamide. DMAP (18 mg, 0.15 mmol) and mercaptoacetic acid (3.2 ml, 46mmol) were added to the obtained solution. The obtained mixture was refluxed for 12 h in a flask equipped with a reflux condenser,then diluted with 0.5 HCl solution (5 ml).The precipitate of 1,3-thiazolidinone 1 was filtered off and washed with hot MeCN (15 ml). When necessary, the product was additionally purified by refluxing a suspension of thiazolidine in MeCN, followed by hot filtration
3-amino-N-benzyl-1-(2,4-dichlorophenyl)-1H-benzo[f]chromene-2-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
With piperidine; In ethanol; for 2h;Reflux;
General procedure: N-benzyl-2-cyanoacetamide (1) was synthesized from benzylamineand ethyl cyanoacetate following the reported procedure[30] (Table 1).A mixture of N-benzyl-2-cyanoacetamide (1 mmol),aromatic aldehydes (1 mmol), 2-naphthol (1 mmol)and piperidine (0.1 mmol) in absolute EtOH (5 ml) wasrefluxed for an appropriate time as shown in Table 2. The reaction progress was monitored by TLC. After completionof the reaction, the mixture was cooled to r.t and thenH2O(5 mL) was added. The solid product was filtered,washed with cold distilled water (2 mL) to obtain essentiallypure products. The solid products were recrystallizedfrom ethanol.The structure of the products was characterized by IR, 1Hand 13C NMR spectra along with elemental analysis data.
3-amino-N-benzyl-1-(3-methoxyphenyl)-1H-benzo[f]chromene-2-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
65%
With piperidine; In ethanol; for 4h;Reflux;
General procedure: N-benzyl-2-cyanoacetamide (1) was synthesized from benzylamineand ethyl cyanoacetate following the reported procedure[30] (Table 1).A mixture of N-benzyl-2-cyanoacetamide (1 mmol),aromatic aldehydes (1 mmol), 2-naphthol (1 mmol)and piperidine (0.1 mmol) in absolute EtOH (5 ml) wasrefluxed for an appropriate time as shown in Table 2. The reaction progress was monitored by TLC. After completionof the reaction, the mixture was cooled to r.t and thenH2O(5 mL) was added. The solid product was filtered,washed with cold distilled water (2 mL) to obtain essentiallypure products. The solid products were recrystallizedfrom ethanol.The structure of the products was characterized by IR, 1Hand 13C NMR spectra along with elemental analysis data.
3-amino-N-benzyl-1-(4-hydroxyphenyl)-1H-benzo[f]chromene-2-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
With piperidine; In ethanol; for 4h;Reflux;
General procedure: N-benzyl-2-cyanoacetamide (1) was synthesized from benzylamineand ethyl cyanoacetate following the reported procedure[30] (Table 1).A mixture of N-benzyl-2-cyanoacetamide (1 mmol),aromatic aldehydes (1 mmol), 2-naphthol (1 mmol)and piperidine (0.1 mmol) in absolute EtOH (5 ml) wasrefluxed for an appropriate time as shown in Table 2. The reaction progress was monitored by TLC. After completionof the reaction, the mixture was cooled to r.t and thenH2O(5 mL) was added. The solid product was filtered,washed with cold distilled water (2 mL) to obtain essentiallypure products. The solid products were recrystallizedfrom ethanol.The structure of the products was characterized by IR, 1Hand 13C NMR spectra along with elemental analysis data.
3-amino-N-benzyl-1-phenyl-1H-benzo[f]chromene-2-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
With piperidine; In ethanol; for 3h;Reflux;
N-benzyl-2-cyanoacetamide (1) was synthesized from benzylamineand ethyl cyanoacetate following the reported procedure[30] (Table 1).A mixture of N-benzyl-2-cyanoacetamide (1 mmol),aromatic aldehydes (1 mmol), 2-naphthol (1 mmol)and piperidine (0.1 mmol) in absolute EtOH (5 ml) wasrefluxed for an appropriate time as shown in Table 2. The reaction progress was monitored by TLC. After completionof the reaction, the mixture was cooled to r.t and thenH2O(5 mL) was added. The solid product was filtered,washed with cold distilled water (2 mL) to obtain essentiallypure products. The solid products were recrystallizedfrom ethanol.The structure of the products was characterized by IR, 1Hand 13C NMR spectra along with elemental analysis data.3 -A m i n o - N - b e n z yl - 1 - p h e nyl - 1 H - b e n z o [ f ]chromene-2-carboxamide (4a): White solid, Yield 75%;mp: 125-126 C. IR (KBr) (numax, cm-1): 3425(NH), 1683(C=O). Anal. calcd. for C27H22N2O2(406.48): C, 79.78; H,5.46; N, 6.89; % found: C, 79.70; H, 5.54; N, 6.84, % dH(400 MHz, CDCl3)8.76 (s, 2H, NH2), 7.66-7.86 (m, 4H, CHarom), 7.53-7.66(m, 3H, CH arom), 7.44-7.53 (d, J = 8 Hz,2H, CH arom), 7.29-7.35 (m, 5H, CH arom and NH), 6.96(t, J = 7.5 Hz, 1H, CH arom), 6.94 (m, 1H, CH arom), 6.84(t, J = 7.5 Hz, 1H, CH arom), 5.20 (s, 1H, CHPh), 4.15 (d,J = 5 Hz, 2H, CH2NH). dC(100 MHz, CDCl3)37.18, 44.16,87.40, 11931, 122.71, 122.99, 123.44, 124.26, 125.43,125.67, 126.54, 128.01, 128.27, 128.43, 128.45, 128.58,128.86, 128.91, 128.97, 129.58, 130.56, 131.05, 131.45,134.84, 143.35, 163.38, 177.39.
3-amino-N-benzyl-1-(4-chlorophenyl)-1H-benzo[f]chromene-2-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
With piperidine; In ethanol; for 2.5h;Reflux;
General procedure: N-benzyl-2-cyanoacetamide (1) was synthesized from benzylamineand ethyl cyanoacetate following the reported procedure[30] (Table 1).A mixture of N-benzyl-2-cyanoacetamide (1 mmol),aromatic aldehydes (1 mmol), 2-naphthol (1 mmol)and piperidine (0.1 mmol) in absolute EtOH (5 ml) wasrefluxed for an appropriate time as shown in Table 2. The reaction progress was monitored by TLC. After completionof the reaction, the mixture was cooled to r.t and thenH2O(5 mL) was added. The solid product was filtered,washed with cold distilled water (2 mL) to obtain essentiallypure products. The solid products were recrystallizedfrom ethanol.The structure of the products was characterized by IR, 1Hand 13C NMR spectra along with elemental analysis data.
3-amino-N-benzyl-1-(4-bromophenyl)-1H-benzo[f]chromene-2-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
72%
With piperidine; In ethanol; for 2.5h;Reflux;
General procedure: N-benzyl-2-cyanoacetamide (1) was synthesized from benzylamineand ethyl cyanoacetate following the reported procedure[30] (Table 1).A mixture of N-benzyl-2-cyanoacetamide (1 mmol),aromatic aldehydes (1 mmol), 2-naphthol (1 mmol)and piperidine (0.1 mmol) in absolute EtOH (5 ml) wasrefluxed for an appropriate time as shown in Table 2. The reaction progress was monitored by TLC. After completionof the reaction, the mixture was cooled to r.t and thenH2O(5 mL) was added. The solid product was filtered,washed with cold distilled water (2 mL) to obtain essentiallypure products. The solid products were recrystallizedfrom ethanol.The structure of the products was characterized by IR, 1Hand 13C NMR spectra along with elemental analysis data.
3-amino-N-benzyl-1-(4-nitrophenyl)-1H-benzo[f]chromene-2-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With piperidine; In ethanol; for 2h;Reflux;
General procedure: N-benzyl-2-cyanoacetamide (1) was synthesized from benzylamineand ethyl cyanoacetate following the reported procedure[30] (Table 1).A mixture of N-benzyl-2-cyanoacetamide (1 mmol),aromatic aldehydes (1 mmol), 2-naphthol (1 mmol)and piperidine (0.1 mmol) in absolute EtOH (5 ml) wasrefluxed for an appropriate time as shown in Table 2. The reaction progress was monitored by TLC. After completionof the reaction, the mixture was cooled to r.t and thenH2O(5 mL) was added. The solid product was filtered,washed with cold distilled water (2 mL) to obtain essentiallypure products. The solid products were recrystallizedfrom ethanol.The structure of the products was characterized by IR, 1Hand 13C NMR spectra along with elemental analysis data.
3-amino-N-benzyl-1-(3-nitrophenyl)-1H-benzo[f]chromene-2-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
With piperidine; In ethanol; for 2h;Reflux;
General procedure: N-benzyl-2-cyanoacetamide (1) was synthesized from benzylamineand ethyl cyanoacetate following the reported procedure[30] (Table 1).A mixture of N-benzyl-2-cyanoacetamide (1 mmol),aromatic aldehydes (1 mmol), 2-naphthol (1 mmol)and piperidine (0.1 mmol) in absolute EtOH (5 ml) wasrefluxed for an appropriate time as shown in Table 2. The reaction progress was monitored by TLC. After completionof the reaction, the mixture was cooled to r.t and thenH2O(5 mL) was added. The solid product was filtered,washed with cold distilled water (2 mL) to obtain essentiallypure products. The solid products were recrystallizedfrom ethanol.The structure of the products was characterized by IR, 1Hand 13C NMR spectra along with elemental analysis data.
3-amino-N-benzyl-1-p-tolyl-1H-benzo[f]chromene-2-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
With piperidine; In ethanol; for 3.5h;Reflux;
General procedure: N-benzyl-2-cyanoacetamide (1) was synthesized from benzylamineand ethyl cyanoacetate following the reported procedure[30] (Table 1).A mixture of N-benzyl-2-cyanoacetamide (1 mmol),aromatic aldehydes (1 mmol), 2-naphthol (1 mmol)and piperidine (0.1 mmol) in absolute EtOH (5 ml) wasrefluxed for an appropriate time as shown in Table 2. The reaction progress was monitored by TLC. After completionof the reaction, the mixture was cooled to r.t and thenH2O(5 mL) was added. The solid product was filtered,washed with cold distilled water (2 mL) to obtain essentiallypure products. The solid products were recrystallizedfrom ethanol.The structure of the products was characterized by IR, 1Hand 13C NMR spectra along with elemental analysis data.
3-amino-N-benzyl-1-(4-methoxyphenyl)-1H-benzo[f]chromene-2-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
With piperidine; In ethanol; for 4h;Reflux;
General procedure: N-benzyl-2-cyanoacetamide (1) was synthesized from benzylamineand ethyl cyanoacetate following the reported procedure[30] (Table 1).A mixture of N-benzyl-2-cyanoacetamide (1 mmol),aromatic aldehydes (1 mmol), 2-naphthol (1 mmol)and piperidine (0.1 mmol) in absolute EtOH (5 ml) wasrefluxed for an appropriate time as shown in Table 2. The reaction progress was monitored by TLC. After completionof the reaction, the mixture was cooled to r.t and thenH2O(5 mL) was added. The solid product was filtered,washed with cold distilled water (2 mL) to obtain essentiallypure products. The solid products were recrystallizedfrom ethanol.The structure of the products was characterized by IR, 1Hand 13C NMR spectra along with elemental analysis data.
methyl (Z)-2-bromo-4,4,4-trifluoro-2-butenoate[ No CAS ]
C14H9F3N2O2[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
82%
General procedure: Under N2 atmosphere, t-BuOK (246 mg, 2.2 mmol) and various acetamides 2 (1.0 mmol) in dry THF (5 mL) were placed in a 10 mL Schlenk flask at -78 C. The suspension was warmed to room temperature for 30 min and recooled to -78 C. (Z)-methyl-bromo-4,4,4-trifluorobut-2-enoate 1 (117 mg, 0.5 mmol) was added at this temperature. The solution was stirred at this temperature until the reaction was completed (usually 15-30 min), followed by adding saturated aqueous NH4Cl solution (10 mL). The solution mixture was extracted with EtOAc (3×10 mL), and the combined organic layer was washed with brine, then, dried over Na2SO4. After removal of solvents under vacuum, the crude product was further purified by silica gel column chromatography (PE:EA = 1:2 v/v) to afford pure product 4.
6-amino-1-benzyl-2-oxo-4-phenyl-1,2-dihydropyridine-3,5-dicarbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
94%
With potassium carbonate; In ethanol; at 90℃; for 0.166667h;Microwave irradiation; Sealed tube; Green chemistry;
General procedure: A mixture of N-alkyl-2-cyano-acetamides 1a-c (2 mmol), aldehydes 2a-f (2 mmol),malononitrile (3) (2 mmol), K2CO3 (2 mmol), and EtOH (2 mL) in a 10 mL septum-capped microwavevials was irradiated under microwave conditions at 90 C, 500 W, 200 rpm, for 10-15 min. Aftercompletion of the reaction, as indicated by TLC, each vial was de-capped and the contents were left tocool to room temperature. Then, the reaction mixture was worked up as described in method I to givecompounds 4a-q. Analytical samples were obtained by recrystallization from MeOH.
6-amino-1-benzyl-2-oxo-4-(p-tolyl)-1,2-dihydropyridine-3,5-dicarbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
With potassium carbonate; In ethanol; at 90℃; for 0.166667h;Microwave irradiation; Sealed tube; Green chemistry;
General procedure: A mixture of N-alkyl-2-cyano-acetamides 1a-c (2 mmol), aldehydes 2a-f (2 mmol),malononitrile (3) (2 mmol), K2CO3 (2 mmol), and EtOH (2 mL) in a 10 mL septum-capped microwavevials was irradiated under microwave conditions at 90 C, 500 W, 200 rpm, for 10-15 min. Aftercompletion of the reaction, as indicated by TLC, each vial was de-capped and the contents were left tocool to room temperature. Then, the reaction mixture was worked up as described in method I to givecompounds 4a-q. Analytical samples were obtained by recrystallization from MeOH.
6-Amino-1-benzyl-4-(3-chlorophenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With potassium carbonate; In ethanol; at 90℃; for 0.2h;Microwave irradiation; Sealed tube; Green chemistry;
General procedure: A mixture of N-alkyl-2-cyano-acetamides 1a-c (2 mmol), aldehydes 2a-f (2 mmol),malononitrile (3) (2 mmol), K2CO3 (2 mmol), and EtOH (2 mL) in a 10 mL septum-capped microwavevials was irradiated under microwave conditions at 90 C, 500 W, 200 rpm, for 10-15 min. Aftercompletion of the reaction, as indicated by TLC, each vial was de-capped and the contents were left tocool to room temperature. Then, the reaction mixture was worked up as described in method I to givecompounds 4a-q. Analytical samples were obtained by recrystallization from MeOH.
6-amino-1-benzyl-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3,5-dicarbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
With potassium carbonate; In ethanol; at 90℃; for 0.183333h;Microwave irradiation; Sealed tube; Green chemistry;
General procedure: A mixture of N-alkyl-2-cyano-acetamides 1a-c (2 mmol), aldehydes 2a-f (2 mmol),malononitrile (3) (2 mmol), K2CO3 (2 mmol), and EtOH (2 mL) in a 10 mL septum-capped microwavevials was irradiated under microwave conditions at 90 C, 500 W, 200 rpm, for 10-15 min. Aftercompletion of the reaction, as indicated by TLC, each vial was de-capped and the contents were left tocool to room temperature. Then, the reaction mixture was worked up as described in method I to givecompounds 4a-q. Analytical samples were obtained by recrystallization from MeOH.
6-amino-1-benzyl-2-oxo-4-(pyridin-3-yl)-1,2-dihydropyridine-3,5-dicarbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
93%
With potassium carbonate; In ethanol; at 90℃; for 0.216667h;Microwave irradiation; Sealed tube; Green chemistry;
General procedure: A mixture of N-alkyl-2-cyano-acetamides 1a-c (2 mmol), aldehydes 2a-f (2 mmol),malononitrile (3) (2 mmol), K2CO3 (2 mmol), and EtOH (2 mL) in a 10 mL septum-capped microwavevials was irradiated under microwave conditions at 90 C, 500 W, 200 rpm, for 10-15 min. Aftercompletion of the reaction, as indicated by TLC, each vial was de-capped and the contents were left tocool to room temperature. Then, the reaction mixture was worked up as described in method I to givecompounds 4a-q. Analytical samples were obtained by recrystallization from MeOH.
6-amino-1-benzyl-2-oxo-4-(pyridin-4-yl)-1,2-dihydropyridine-3,5-dicarbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
With potassium carbonate; In ethanol; at 90℃; for 0.183333h;Microwave irradiation; Sealed tube; Green chemistry;
General procedure: A mixture of N-alkyl-2-cyano-acetamides 1a-c (2 mmol), aldehydes 2a-f (2 mmol),malononitrile (3) (2 mmol), K2CO3 (2 mmol), and EtOH (2 mL) in a 10 mL septum-capped microwavevials was irradiated under microwave conditions at 90 C, 500 W, 200 rpm, for 10-15 min. Aftercompletion of the reaction, as indicated by TLC, each vial was de-capped and the contents were left tocool to room temperature. Then, the reaction mixture was worked up as described in method I to givecompounds 4a-q. Analytical samples were obtained by recrystallization from MeOH.
General procedure: A mixture of 1.5 g (10 mmol) 1H-indole-3-carbaldehyde (1) and 10 mmol of CH acid 4a-4f in 20 mL of ethanol containing 3 drops of morpholine was stirred for 4 h at 20C. The mixture was left to stand for 24 h, and the precipitate was filtered off and washed with ethanol and hexane.
(2E)-N-benzyl-2-cyano-3-(7-methoxy-4-oxo-2-phenyl-4H-chromen-8-yl)acrylamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With triethylamine; In ethanol;Reflux;
General procedure: To a solution of suitable N-substituted cyanoacetamide 7(a-q)(3.1 mmol) and 5 (1.5 mmol) in EtOH (10 mL), was added tri ethylamine(0.1 mmol) at RT and the resultant solution was stirred to refluxfor 2-3 h. Then, the solution was cooled to RT. The precipitate formationserved as an indication of product formation. The formed productwas filtered and rinsed with icy EtOH (3-5 mL) [21], to obtain the finalproducts 8(a-q) in 51-81% yield.
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