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CAS No. : | 178686-24-3 | MDL No. : | MFCD00058678 |
Formula : | C9H9NO5 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | MDWLNBVKBMKTKN-UHFFFAOYSA-N |
M.W : | 211.17 | Pubchem ID : | 584878 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302 | Packing Group: | N/A |
GHS Pictogram: |
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* 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 |
---|---|---|
With piperidine; acetic acid; In toluene; at 100 - 115℃; for 15.0h;Heating / reflux; | Charge <strong>[178686-24-3]3-ethoxy-4-hydroxy-5-nitrobenzaldehyde</strong> 20g (0. 0947mole) of the formula 2 where R= ethyl and N, N-diethylamino cyanoacetamide of the formula (3) 14. 6g, (0.1042), acetic acid 3.13g and piperidine 4.45g along with toluene 200ml and heated to reflux temperature of about 100-115 C with continuous removal of water azeotrophically 15 hours. After the reaction is over the reaction mixture is concentrated to a volume of 20-30ml quenched in to dilute hydrochloric acid and chilled water 200ml and stirred for 60 minutes. The precipitated solid was filtered and dried to get 30g (95%), the HPLC purity is 94% (including isomer) of N, N-DIETHYL - 2-CYANO-3- (-3-ETHOXY-4-HYDROXY-5 NITROPHENYL) ACRYLAMIDE. The product is used as such directly to the. next stage. MR = 110.1- 117. 2 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With nitric acid; In water; acetic acid; for 17.0h; | a). 3-Ethoxy-4-hydroxy-5-nitro-benzaldehyde To a solution of 3-ethoxy-4-hydroxybenzaldehyde (5 g) in acetic acid (50 ml) was added nitric acid (1.4 ml) in 2 portions. The resulting suspension was stirred for 17 h. The solid was collected by filtration, washed with water and dried in vacuo.Yield: 5.07 g. | |
With nitric acid; acetic acid; for 17.0h; | Example 14; Propane- 1 -sulfonic acid r5-(3-cvano-2-methyl-5-oxo-7-propyl-l,4,5,6,7,8-hexahvdro- quinolin-4- vD-3 -ethoxy-2-(3 -methoxy-benzyloxy) -phenyll -amide(a). 3-Ethoxy-4-hvdroxy-5-nitro-benzaldehvdeTo a solution of 3-ethoxy-4-hydroxybenzaldehyde (5 g) in acetic acid (50 ml) was added nitric acid (1.4 ml) in 2 portions. The resulting suspension was stirred for 17 h. The solid was collected by filtration, washed with water and dried in vacuo.Yield: 5.07 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetra-(n-butyl)ammonium iodide; potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 1.5h; | Example 4; 4-r3-Ethoxy-4-(3-methoxy-benzyloxy)-5-nitro-phenyll-2-methyl-5-oxo-7-propyl- 1,4,5, 6,7,8-hexahvdro-quinoline-3-carbonitrile(a). 3-Ethoxy-4-(3-methoxy-benzyloxy)-5-nitro-benzaldehvdeA mixture of <strong>[178686-24-3]5-nitro-3-ethoxy-4-hydroxybenzaldehyde</strong> (100 mg), 3-methoxybenzyl bromide (73 mul), potassium carbonate (144 mg) and tetrabutylammonium iodide (10 mg) in DMF (5 ml) was stirred at 60 0C for 90 min. The mixture was poured into water and extracted with ethyl acetate. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by chromatography on silicagel in heptane/ethyl acetate 2/1 (v/v) as eluent.Yield: 43 mg. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; for 17.0h;Heating / reflux; | (b). 4-(3-Ethoxy-4-hvdroxy-5-nitro-phenviy2-methyl-5-oxo-7-propyl-l,4,5, 6,7,8- hexahydro-quinoline-3 -carbonitrileA mixture of <strong>[178686-24-3]3-ethoxy-4-hydroxy-5-nitro-benzaldehyde</strong> (1.5 g), 3-aminocrotonitrile (584 mg) and 5-propylcyclohexane-l,3-dione (1.09 g) in ethanol (60 ml) was heated at reflux for 17 h. The mixture was concentrated in vacuo. The residue was purified by chromatography on silicagel in heptane/ethyl acetate 1/0 - > 0/1 (v/v) as eluent. EPO <DP n="43"/>Yield: 1.3 g. MS-ESI: [M+H]+ = 412.3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; for 17.0h;Heating / reflux; | (b). 4-(3-Ethoxy-4-hydroxy-5-nitro-phenyl)-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile A mixture of <strong>[178686-24-3]3-ethoxy-4-hydroxy-5-nitro-benzaldehyde</strong> (1.5 g), 3-aminocrotonitrile (584 mg) and 5-propylcyclohexane-1,3-dione (1.09 g) in ethanol (60 ml) was heated at reflux for 17 h. The mixture was concentrated in vacuo. The residue was purified by chromatography on silicagel in heptane/ethyl acetate 1/0?0/1 (v/v) as eluent.Yield: 1.3 g. MS-ESI: [M+H]+=412.3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13% | With cycl-isopropylidene malonate; acetic acid;Reflux; | [00159] A mixture of 1,2-diphenylethanone (150 mg, 0.76 mmol), 3-ethoxy-4- hydroxy- 5 -nitrobenzaldehyde (194 mg, 0.92 mmol), meldrum's acid (132 mg, 0.92 mmol) and ammonium acetate (71 mg, 0.92 mmol) in acetic acid (5 mL) was refluxed overnight. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (EtOAc : PE=2: 1) and prep-HPLC (0.1% TFA as additive) to afford Compound 1 as yellow solid (40 mg, yield: 13%). 1H NMR (DMSO- 6 300 MHz): delta 10.20 (s, 1H), 9.60 (s, 1H), 7.47 (d, J = 3.0 Hz, 1H), 7.24-7.18 (m, 6H), 7.01-6.96 (m, 3H), 6.79 (d, J = 8.1 Hz, 2H), 4.06 (q, J = 6.0 Hz, 2H), 3.96 (d, J = 5.1 Hz, 1H), 3.14-3.07 (m, 2H),1.31 (t, J = 1.2 Hz, 3H); MS (ESI): m/z 430.9 [M+H+]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12% | With cycl-isopropylidene malonate; acetic acid;Reflux; Inert atmosphere; | [00160] A mixture of l-(pyridin-3-yl)-2-(thiophen-3-yl)ethanone (Intermediate 1, seeExample 18 for synthesic description of all intermediates) (230 mg, 1.1 mmol), 3-ethoxy-4- hydroxy- 5 -nitrobenzaldehyde (296 mg, 1.4 mmol), meldrum's acid (202 mg, 1.4 mmol) and AcONH4 (108 mg, 1.4 mmol) in AcOH (3 mL) was refluxed under N2 overnight. The mixture was concentrated under reduced pressure and the residue was purified by prep-HPLC (0.1% TFA as additive) to give Compound 2 (60 mg, 12%). 1H NMR (MeOD 400 MHz): delta 8.70 (d, J = 5.2 Hz, 1H), 8.67 (s, 1H), 8.30 (d, J = 8.0 Hz, 1H), 7.90-7.62 (m, 1H), 7.72-7.60 (m, 1H), 7.27-7.24 (m, 2H), 6.94-6.92 (m, 1H), 6.58 (d, J = 4.8 Hz, 1H), 4.20-4.11 (m, 3H), 3.30-3.25 (m, 1H), 2.79-2.74 (dd, J = 16.2, 3.2 Hz, 1H), 1.45 (t, J = 6.8 Hz, 3H). MS (ESI): m/z 438.3 [M+l]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6% | With cycl-isopropylidene malonate; acetic acid;Reflux; Inert atmosphere; | [00162] A mixture of l-(l-methyl-lH-pyrazol-4-yl)-2-(thiophen-3-yl)ethanone(Intermediate 3) (150 mg, 0.73 mmol), <strong>[178686-24-3]3-ethoxy-4-hydroxy-5-nitrobenzaldehyde</strong> (185 mg, 0.87 mmol), meldrum's acid (125 mg, 0.87 mmol) and AcONH4 (84 mg, 1.1 mmol) in AcOH (3 mL) was refluxed under N2 overnight. The mixture was concentrated under reduced pressure and the residue was purified by prep-HPLC (0.1% TFA as additive) to giveCompound 4 as yellow solid (20 mg, 6%). 1H NMR (DMSO- 6, 400 MHz): delta 10.20 (s, 1H), 9.43 (s, 1H), 7.62 (s, 1H), 7.42-7.36 (m, 2H), 7.19-7.11 (m, 1H), 7.06 (s, 2H), 6.70-6.68 (m, 1H), 4.11-4.03 (m, 2H), 3.95-3.92 (m, 1H), 3.77 (s, 3H), 3.08 (dd, J = 16.4, 7.6 Hz, 1H), 2.60-2.52 (m, 1H), 1.34 (t, J = 6.8 Hz, 3H). MS (ESI): m/z 440.9 [M+l]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With hydrogenchloride; In ethanol; water;Reflux; | 00161] A mixture of 2-phenyl-l-p-tolylethanone (65 mg, 0.31 mmol), 3-ethoxy-4- hydroxy-5-nitrobenzaldehyde (54 mg, 0.26 mmol), urea (56 mg, 0.93 mmol), andconcentrated HC1 solution (0.03 mL, 0.31 mmol) in EtOH (5 mL) was refluxed overnight. The mixture was evaporated in vacuo and the residue was purified by preparative HPLC to give compound 16 (455.19 mg, yield 40%). 1H NMR (DMSO- d6 400 MHz): delta 10.28 (s, 1H), 8.64 (s, 1H), 7.51 (s, 1H), 7.42 (s, 1H), 7.17 (s, 1H), 7.08-6.96 (m, 7H), 6.80 (d, J = 6.8 Hz, 2H), 5.14 (d, J = 2.4 Hz, 1H), 4.05-3.98 (m, 2H), 2.23 (s, 3H), 1.31 (t, J = 6.8 Hz, 3H); MS (ESI): m/z 446.2 [M+l]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13% | With hydrogenchloride; In ethanol; water;Reflux; | 00177] A mixture of l-(3-fluorophenyl)-2-phenylethanone (100 mg, 0.47 mmol), 3- ethoxy-4-hydroxy-5-nitrobenzaldehyde (82 mg, 0.39 mmol), urea (70 mg, 1.17 mmol), and concentrated HC1 solution (0.03 mL, 0.39 mmol) in EtOH (5 mL) was refluxed overnight. The mixture was evaporated in vacuo and purified by preparative HPLC to give Compound 32 (22.35 mg, yield 13%) as a yellow solid. 1H NMR (DMSO-d6 400 MHz): delta 10.28 (s, IH), 8.79 (s, IH), 7.56 (s, IH), 7.42 (s, IH), 7.30-7.25 (m, IH), 7.16 (s, IH), 7.12-6.99 (m, 6H), 6.86 (d, J = 1.6 Hz, 2H), 5.23 (d, J = 2.4 Hz, IH), 4.04 (q, J = 7.2 Hz, 2H), 1.33 (t, J = 1.2 Hz, 3H); MS (ESI): m/z 450.0 [M+l]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With hydrogenchloride; In ethanol; water;Reflux; | [00184] A mixture of l-(3-fluoro-4-methoxyphenyl)-2-phenylethanone (100 mg, 0.41 mmol), <strong>[178686-24-3]3-ethoxy-4-hydroxy-5-nitrobenzaldehyde</strong> (72 mg, 0.34 mmol), urea (61 mg, 1.02 mmol), and concentrated HCl solution (0.03 mL, 0.34 mmol) in EtOH (5 mL) was refluxed overnight. The mixture was evaporated in vacuo, and the residue was purified by preparative HPLC to give Compound 39 (78 mg, yield 48%). 1H NMR (DMSO- 6 400 MHz): delta 10.28 (s, 1H), 8.71 (s, 1H), 7.53 (s, 1H), 7.42 (s, 1H), 7.17 (s, 1H), 7.10-7.01 (m, 5H), 6.95 (d, J = 92 Hz, 1H), 6.85 (d, J = 6.8 Hz, 2H), 5.18 (s, 1H), 4.08-4.01 (m, 2H), 3.79 (s, 3H), 1.33 (t, J = 7.2 Hz, 3H); MS (ESI): m/z 480.0 [M+l]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | With hydrogenchloride; In ethanol; water; for 48.0h;Reflux; | 00192] To a solution of l-(3,4-dichlorophenyl)-2-phenylethanone (Intermediate 19)(100 mg, 0.38 mmol), <strong>[178686-24-3]3-ethoxy-4-hydroxy-5-nitrobenzaldehyde</strong> (74.4 mg, 0.38 mmol), and urea (68.5 mg, 1.14 mmol) in 5 mL of ethanol was added 0.2 mL of concentrated HC1 solution, and the mixture was refluxed for 2 days. After the solvent was removed under reduced pressure, the residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile + 0.1% trifluoroacetic acid in water + 0.1% trifluoroacetic acid, over 15 min.) to give Compound 47 (32 mg, yield 17.0%). 1H NMR (DMSO- 6 300 MHz) delta 10.28 (s, 1H), 8.85 (s, 1H), 7.58 (s, 1H), 7.48 (t, J = 1.5 Hz, 2H), 7.41 (d, J = 1.8 Hz, 1H), 7.13-7.05 (m, 5H), 6.88 (t, J = 1.8 Hz, 2H), 5.25 (d, J = 2.1 Hz, 1H), 4.02 (m, 2H), 1.32 (t, J = 6.9 Hz, 3H); MS(ESI): m/z 499.9 [M+l]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38.3% | With hydrogenchloride; In ethanol; water; at 79℃; for 80h; | 00222] A mixture of l-phenyl-2-(pyridin-4-yl)ethanone (Intermediate 36) (100 mg,0.507 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (107 mg, 0.507 mmol), urea (91.3 mg, 4.587 mmol), and concentrated hydrochloric acid (0.3 mL) in ethanol (1 mL) was refluxed at 79C for 80 h. After being cooled down to room temperature, the mixture was evaporated, and purified by preparative HPLC to give Compound 74 (80.1 mg, yield 38.3%). 1H NMR (DMSO- 6 400MHz): delta 10.41 (s, IH), 9.57 (s, IH), 8.34 (d, J = 6.4 Hz, 2H), 8.02 (s, IH), 7.50-7.42 (m, 4H), 7.39 (d, J = 1.2 Hz, 2H), 7.34 (d, J = 1.6 Hz, IH), 7.06 (d, J = 6.4 Hz, 2H), 5.39 (d, J = 3.2 Hz, IH), 4.15-4.10 (m, 2H), 1.38-1.35 (m, 3H); MS (ESI): m/z 433.0 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43.7% | With hydrogenchloride; In ethanol; water; at 78℃; for 70.0h; | [00233] A mixture of l-phenyl-2-(pyridin-3-yl)ethanone (Intermediate 42) (200 mg,1.01 mmol), <strong>[178686-24-3]3-ethoxy-4-hydroxy-5-nitrobenzaldehyde</strong> (213.3 mg, 1.01 mmol), urea (181.8 mg, 3.03 mmol), and concentrated hydrochloric acid solution (0.5 mL) in ethanol (2 mL) was refluxed at 78C for 70 h. After being cooled down to room temperature, the reaction mixture was evaporated, and the residue was purified by preparative HPLC to giveCompound 84 (191.1 mg, yield 43.7%). 1H NMR (DMSO- 6 400MHz): delta 10.34 (s, 1H), 9.06 (s, 1H), 8.35-8.33 (m, 1H), 8.10 (d, J = 2.0 Hz, 1H), 7.72 (s, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.45-7.39 (m, 2H), 7.33-7.23 (m, 6H), 5.39 (d, J = 2.8 Hz, 1H), 4.11-4.06 (m, 2H), 1.36-1.33 (m, 3H); MS (ESI): m/z 433.0 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.5% | With hydrogenchloride; In ethanol; water; for 96.0h;Reflux; | 00168] To a solution of 2-(3-methoxyphenyl)-l-phenylethanone (400 mg, 1.77 mmol), <strong>[178686-24-3]3-ethoxy-4-hydroxy-5-nitrobenzaldehyde</strong> (374 mg, 1.77 mmol) and urea (244 mg, 5.31 mmol) in 20 mL of ethanol was added 0.2 mL of concentrated HCl, then the mixture was stirred at reflux for 4 days. After the solvent was removed under reduced pressure, the residue was purified by HPLC (35-65% acetonitrile + 0.1% trifluoroacetic acid in water, over 15 min.) and then purified by thin layer chromatography (PE:EtOAc=l :2) further to give Compound 23 (20 mg, yield 2.5%). 1H NMR (CD3OD 400 MHz): delta 7.43 (s, IH), 7.17 (s, 5H), 6.86-6.82 (m, 2H), 6.48 (d, J=6.4 Hz, IH), 6.40 (d, J=8.0 Hz, IH), 6.30 (s, IH), 5.03 (s, IH), 3.91-3.89 (m, 2H), 3.37 (s, 3H), 1.30 (t, J=7.2 Hz, 3H); MS (ESI): mJz 462.3 [M+l]+. |
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