Structure of 582-80-9
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CAS No. : | 582-80-9 |
Formula : | C14H11NO3 |
M.W : | 241.24 |
SMILES Code : | O=C(O)C1=CC=C(NC(C2=CC=CC=C2)=O)C=C1 |
MDL No. : | MFCD00451153 |
InChI Key : | UZKKMWJMAJGMPF-UHFFFAOYSA-N |
Pubchem ID : | 252597 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 67.62 |
TPSA ? Topological Polar Surface Area: Calculated from |
66.4 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.73 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.15 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.45 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.55 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.0 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.18 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.92 |
Solubility | 0.29 mg/ml ; 0.0012 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.18 |
Solubility | 0.161 mg/ml ; 0.000666 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.29 |
Solubility | 0.0122 mg/ml ; 0.0000507 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.25 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.29 |
* 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 |
---|---|---|
96.7% | PREPARATION EXAMPLE EX45 (0284) This example demonstrates the production of 4-benzoylamino benzoic acid having the following structure (0285) (0286) In a 1 L beaker with mechanical stirring, 27.4 g of 4-aminobenzoic acid (0.2 mol) was mixed in 300 mL of DI H2O. Then, 21.2 g (0.2 mol) of sodium carbonate was added until the pH value became 9.1 and all the 4-amino benzoic acid dissolved in the water. (0287) Then, 56.24 g (0.4 mol) of benzoyl chloride was added dropwise to the beaker at room temp. The reaction was stirred overnight. A solid formed during the reaction, and the pH stabilized at 4.0. The pH was further lowered to about 2 with hydrochloric acid. The product was collected by filtration and washed with hot water to remove excess benzoic acid. The solid product was dried in an oven at 110° C. and 44.21 g of the product was obtained (yield 96.7percent). | |
81% | With pyridine; at 20℃; | General procedure: Aromatic halides (1.0 equivalent) were added dropwise to the stirred solution of aminobenzoic acids (200 mg) in pyridine. Mixtures were stirred at room temperature for about all target derivatives except of benzyl based derivative. The pH of reaction mixtures was kept basic using pyridine. Progress of the reaction was monitored using TLC plates. Upon complete formation of target compounds, the desired products were filtered as white precipitates. For benzyl based derivatives reaction mixture was refluxed for more than 24 hours and product was obtained by evaporating the solvent under vacuum. |
General procedure: A solution of aminobenzoic acid in dichloromethane at room temperature was treated with triethylamine and stirred for 30 min to obtain a pellucid solution. The substituted benzoyl chloride was then slowly added. After precipitates were observed, the mixture was stirred at room temperature for another 2 h. The suspension was concentrated under reduced pressure, and the residue was purified by hot acetic acid to give compounds 4a-f. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The following specific retinoids are also useful in the method of this invention:...4-[3-(3,4-Diethyl-phenyl)-3-methyl-oxiranyl]benzoic acid;4-[3-Methyl-3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-oxiranyl]-benzoic acid;4-Benzoylamino-benzoic acid;4-(3-tert-Butyl-benzoylamino)-benzoic acid;... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; chloroformic acid ethyl ester; at 10 - 20℃; for 2.5h; | 20. Og (0. 16MOL) of benzoic acid was dissolved in 250M. OF PYRIDINE and then was cooled in a ice bath of 10C. Thereto, 23. 1g (0. 21MOL) of ethyl CHLOROFORMATE was added dropwise for 30 minutes. The mixture was stirred at room temperature for 2 hours and then filtered to remove salts, to give an anhydride (30.2g, 0. 15MOL). 24. 1G (0. 16MOL) of metyl aminobenzoate was dissolved in 250MQ of pyridine and then was cooled in a ice bath of 10 C. Thereto, the anhydride formed in the previous step was added dropwise for 30 minutes. The mixture was stirred for another 2 hours. After distillation of the solvent, the residue was dissolved in 300MQ of ethyl acetate. The ethyl acetate solution was washed with 5percent hydrochloric acid and with distilled water, dried over magnesium sulfate, decolorized with active charcoal, and then filtered. The filtrate was dried under reduced pressure, to give methyl 4- (PHENYLCARBONYLAMINO) benzoate (34.7g, 85percent yield) as a pale yellow solid. Subsequently, 34.7g of methyl 4- (phenylcarbonylamino) benzoate was dissolved in 500MQ of methanol and thereto 50MQ OF 10percent KOH was added. After stirring for 3 hours, the mixture was neutralized with hydrochloric acid and then filtered, to give an acid compound, 4- (phenylcarbonylamino) benzoic acid (26.2g, 80percent yield). 4- (phenylcarbonylamino) benzoic acid formed (24. 1g, 0. 10MOL) was dissolved in 200MQ of pyridine and then was cooled in a ice bath of 10C. Thereto, 22.9g (0. 13MOL) of ethyl CHLOROFORMATE was added dropwise for 30 minutes. The mixture was stirred at room temperature for 2 hours and then filtered to remove salts, to give an anhydride (38. 7g, 0. 12MOL). 6.9g (0. LOMOL) of hydroxylamine hydrochloride was dissolved in LOOM-C of pyridine and then was cooled in a ice bath of 10C. Thereto, the anhydride formed in the previous step was added dropwise for 30 minutes. The mixture was stirred for another 2 hours. After distillation of the solvent, the residue was dissolved in 300MQ of ethyl acetate. The ethyl acetate solution was washed with 5percent hydrochloric acid and with distilled water, dried over magnesium sulfate, decolorized with active charcoal, and then filtered. The filtrate was dried under reduced pressure, to give a final product, N- [4- (N-HYDROXYCARBAMOYL) phenyl] benzamide (16. 6g, 65percent yield) as a pale yellow solid. TLC (in ethyl acetate: hexane = 1: 1); RF= 0. 53 H-NMR (DMSO-d6): 611. 23 (s, 1H), 10.39 (s, 1H), 9.04 (s, 1H), 8.01 (m, 5H), 7.64 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With lithium hydroxide monohydrate; In tetrahydrofuran; methanol; water; at 20℃; for 17h; | b) 4-Benzamidobenzoic acid (A 13) To a solution of methyl 4-benzamidobenzoate A12 (1.00 g, 3.92 mmol) in 4: 1 : 1 v/v THF/MeOH/water (30 mL) was added LiOH H20 (0.505 g, 1 1.8 mmol). The solution was stirred at room temperature for 17 hours and then acidified with 1 M aqueous HCI. The precipitate was collected by filtration to give the title compound (0.886 g, 94percent) as a white solid. H NMR (400 MHz, cf DMSO) delta 10.54 (br s, 1 H), 8.00 - 7.88 (m, 6H), 7.65 - 7.59 (m, 1 H), 7.59 - 7.51 (m, 2H). LCMS-A rt 4.84 min, m/z (positive ion) 242.1 [M+H]+, m/z (negative ion) 240.1 [M-H]\ |
80% | With potassium hydroxide; water; In methanol; for 3h; | 20. Og (0. 16MOL) of benzoic acid was dissolved in 250M. OF PYRIDINE and then was cooled in a ice bath of 10C. Thereto, 23. 1g (0. 21MOL) of ethyl CHLOROFORMATE was added dropwise for 30 minutes. The mixture was stirred at room temperature for 2 hours and then filtered to remove salts, to give an anhydride (30.2g, 0. 15MOL). 24. 1G (0. 16MOL) of metyl aminobenzoate was dissolved in 250MQ of pyridine and then was cooled in a ice bath of 10 C. Thereto, the anhydride formed in the previous step was added dropwise for 30 minutes. The mixture was stirred for another 2 hours. After distillation of the solvent, the residue was dissolved in 300MQ of ethyl acetate. The ethyl acetate solution was washed with 5percent hydrochloric acid and with distilled water, dried over magnesium sulfate, decolorized with active charcoal, and then filtered. The filtrate was dried under reduced pressure, to give methyl 4- (PHENYLCARBONYLAMINO) benzoate (34.7g, 85percent yield) as a pale yellow solid. Subsequently, 34.7g of methyl 4- (phenylcarbonylamino) benzoate was dissolved in 500MQ of methanol and thereto 50MQ OF 10percent KOH was added. After stirring for 3 hours, the mixture was neutralized with hydrochloric acid and then filtered, to give an acid compound, 4- (phenylcarbonylamino) benzoic acid (26.2g, 80percent yield). 4- (phenylcarbonylamino) benzoic acid formed (24. 1g, 0. 10MOL) was dissolved in 200MQ of pyridine and then was cooled in a ice bath of 10C. Thereto, 22.9g (0. 13MOL) of ethyl CHLOROFORMATE was added dropwise for 30 minutes. The mixture was stirred at room temperature for 2 hours and then filtered to remove salts, to give an anhydride (38. 7g, 0. 12MOL). 6.9g (0. LOMOL) of hydroxylamine hydrochloride was dissolved in LOOM-C of pyridine and then was cooled in a ice bath of 10C. Thereto, the anhydride formed in the previous step was added dropwise for 30 minutes. The mixture was stirred for another 2 hours. After distillation of the solvent, the residue was dissolved in 300MQ of ethyl acetate. The ethyl acetate solution was washed with 5percent hydrochloric acid and with distilled water, dried over magnesium sulfate, decolorized with active charcoal, and then filtered. The filtrate was dried under reduced pressure, to give a final product, N- [4- (N-HYDROXYCARBAMOYL) phenyl] benzamide (16. 6g, 65percent yield) as a pale yellow solid. TLC (in ethyl acetate: hexane = 1: 1); RF= 0. 53 H-NMR (DMSO-d6): 611. 23 (s, 1H), 10.39 (s, 1H), 9.04 (s, 1H), 8.01 (m, 5H), 7.64 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 20h; | EXAMPLE 44-(Benzoylamino)-N-[2-(N,N-dimethylamino)methyl-6-tetralinyl]benzamide; 6-Amino-2-(N,N-dimethylamino)methyltetralin hydrochloride (139 mg), 4-benzoylaminobenzoic acid (121 mg), WSCD (0.13 ml), HOBt (92 mg), triethylamine (0.14 ml) and DMAP (61 mg) were added to DMF (4 ml). After the reaction mixture was shaken at room temperature for 20 hours using a shaker, the reaction mixture was poured into water, and extraction was conducted using ethyl acetate-THF (1:1). The organic layer was washed with water, saturated sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried, and then concentrated. The resulting crude crystal was washed with hexane, to give the titled compound (181 mg).Melting point: 241-242° C.Washing solvent: hexane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 3h; | General procedure: A suspension of 10A,10B or 10C (1 equiv), 3-nitro-4-(2-(phenylthio)ethylamino) benzenesulfonamide7 (1 equiv), DMAP (0.5equiv) and EDCI (1-2 equiv) in CH2Cl2 were stirred for 3 h. The reaction mixture was diluted with 10 volumes CH2Cl2. The organic phase was washed sequentially with1M HCl , saturated aqueous NaHCO3 and brine, dried over MgSO4 , filtered and concentrated . The crude reaction mixture was purified by column chromatography or gel chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With methanol; sodium hydroxide; In tetrahydrofuran; at 20℃; for 2h; | A suspension of 10j(0.14g,0.57mmol), 3-nitro-4-(2-(phenylthio)ethylamino) benzenesulfonamide 7 (0.2g,0.57mmol, DMAP (0.034g,0.285mmol) and EDCI 0.24g,1.14mmol in 10mL CH2Cl2 were stirred for 3 h. The reaction mixture was diluted with 100mL CH2Cl2. The organic phase was washed sequentially with1M HCl, saturated aqueous NaHCO3 and brine, dried over MgSO4, filtered and concentrated. The crude reaction mixture was purified by gel chromatography and yielded 11j (2g, 90percent).Yellow solid , total yield :21.57percent,mp 162164°C; 1H NMR (DMSO, 500 MHz, delta): 3.27-3.29 (t,2H, J=6.5Hz ,S-CH2), 3.60-3.69 (t,2H, J=6.5Hz , N-CH2), 7.17-7.56 (m,9H, Ar-H), 7.89-7.95 (m,7H, Ar-H), 8.62 (s , 1H , Ar-H ), 8.79 (m ,1H , NH ),10.54 (s, 1H, ArNHCO),12.34 (s,1H, SO2NHCO ) ;ESI-MS m/z575.98 (M-H)- | |
With water; sodium hydroxide; In methanol; at 20℃; for 2h; | The product of Example 10, Step 1, was placed in 200 mL of methanol,To this was added 1 N aqueous NaOH (110 mL, 110 mmol)Stir at room temperature for 2 hours.Steamed methanol,The aqueous phase was extracted with 200 mL of ethyl acetate,Repeat twice.The pH of the remaining aqueous phase was adjusted to 2-3 with 2N hydrochloric acid.Extracted with ethyl acetate (300 mL x 3).Combine organic phase,And dried over anhydrous sodium sulfate for 2 hours.filter,Filter out desiccant,The filtrate was evaporated to dryness under a rotary evaporator,Get class white solid,The resulting product was purified,Directly for the next step reaction. | |
With water; sodium hydroxide; In methanol; at 20℃; for 2h; | The product of Example 13, Step 1, was placed in 200 mL of methanol,To this was added 1 N aqueous NaOH (110 mL, 110 mmol)Stir at room temperature for 2 hours.The methanol was evaporated to dryness and the aqueous phase was extracted with 200 mL of ethyl acetate and repeated twice.The pH of the remaining aqueous phase was adjusted to 2-3 with 2N hydrochloric acid.Extracted with ethyl acetate (300 mL x 3).The organic phases were combined and dried over anhydrous sodium sulfate for 2 hours.Filtering and filtering the desiccant, the filtrate is evaporated to dryness by rotary evaporator,The resulting product was purified as a white solid and the product was used directly in the next step. |
With water; sodium hydroxide; In methanol; at 20℃; for 2h; | The product of Example 13, Step 1, was placed in 200 mL of methanol,To this was added 1 N aqueous NaOH (110 mL, 110 mmol)Stir at room temperature for 2 hours.Methanol was evaporated to dryness,The aqueous phase was extracted with 200 mL of ethyl acetate,Repeat twice.The pH of the remaining aqueous phase was adjusted to 2-3 with 2N hydrochloric acid.Extracted with ethyl acetate (300 mL x 3).Combine organic phase,And dried over anhydrous sodium sulfate for 2 hours.filter,Filter out desiccant,The filtrate was evaporated to dryness under a rotary evaporator,Get class white solid,The resulting product was purified,Directly for the next step reaction. | |
With water; sodium hydroxide; In methanol; at 20℃; for 2h; | The product obtained in Example 1, Step 1, was placed in 200 mL of methanol,To this was added 1 N NaOH aqueous solution (110 mL, 110 mmol)Stir at room temperature for 2 hours. The methanol was evaporated to dryness and the aqueous phase was extracted with 200 mL of ethyl acetateRepeat twice. The pH of the remaining aqueous phase was adjusted to 2-3 with 2N hydrochloric acid.Extracted with ethyl acetate (300 mL x 3). Combined organic phase,And dried over anhydrous sodium sulfate for 2 hours. Filter, filter desiccant,The filtrate was evaporated to dryness under reduced pressure on a rotary evaporator to give an off-white solid,The resulting product was used directly in the next step without purification. |
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