Structure of 601-89-8
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 601-89-8 |
Formula : | C6H5NO4 |
M.W : | 155.11 |
SMILES Code : | OC1=CC=CC(O)=C1[N+]([O-])=O |
MDL No. : | MFCD00007124 |
InChI Key : | ZLCPKMIJYMHZMJ-UHFFFAOYSA-N |
Pubchem ID : | 11760 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 39.31 |
TPSA ? Topological Polar Surface Area: Calculated from |
86.28 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.24 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.56 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.01 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.3 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.25 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.45 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.12 |
Solubility | 1.17 mg/ml ; 0.00755 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.98 |
Solubility | 0.162 mg/ml ; 0.00104 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.61 |
Solubility | 37.7 mg/ml ; 0.243 mol/l |
Class? Solubility class: Log S scale |
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 |
No |
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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.14 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 |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
2.0 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) |
1.67 |
* 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 |
---|---|---|
99% | With potassium carbonate; In acetone; for 1.0h;Inert atmosphere; Reflux; | To a solution of 2-nitroresorcinol 49 (4.80 g, 30.9 mmol) in acetone (30 mL) was added K2CO3 (21.39 g, 155 mmol) under nitrogen atmosphere. Dimethylsulfate (8.80 mL, 92.8 mmol) was then added and the mixture obtained was heated to reflux for 1 h. After cooling to room temperature, the solvent was removed in vacuo. The solid obtained was washed with triethylamine and water, then filtered and dried (MgSO4) to give pure compound 5055 (5.6 g, 99%) as a white solid; TLC Rf (EtOAc) = 0.73; 1H NMR (CDCl3, 400 MHz) δ (ppm) 3.88 (s, 6H, 2OCH3), 6.63 (d, J = 8.6 Hz, 2H, ArH), 7.33 (t, J = 8.6 Hz, 1H, ArH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With potassium carbonate; In acetone; at 60 - 70℃; | MeI (3.0 mL, 48.3 mmol) was added to mixture of 77 (2.50 g, 16.1 mmol) and K2CO3 (4.46 g, 325 mesh, 32.3 mmol) in acetone (250 mL). The reaction mixture was heated to 60-70 C. (bath temperature) over night under N2. The mixture was concentrated in vacuo and the residue was partitioned between EtOAc (200 mL) and water (100 mL). The aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo to yield 78 as a yellow solid (2.87 g, 97%) which was used in the next step without further purification. |
With potassium carbonate; In acetone;Heating; Inert atmosphere; | 1,3-Dimethoxy-2-nitro-benzene (78) MeI (3.0 mL, 48.3 mmol) was added to mixture of 77 (2.50 g, 16.1 mmol) and K2CO3 (4.46 g, 325 mesh, 32.3 mmol) in acetone (250 mL). The reaction mixture was heated to 6070 C. (bath temperature) over night under N2. The mixture was concentrated in vacuo and the residue was partitioned between EtOAc (200 mL) and water (100 mL). The aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo to yield 78 as a yellow solid (2.87 g, 97%) which was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | With sodium hydroxide; In water; at 40℃; for 0.25h; | Dimethylsulfate (2.7 mL, 0.058 mmol) was added carefully to 2-nitrobenzene-1,3-diol (2.5 g, 0.232 mmol) and the mixture was stirred vigorously while 10% NaOH solution (21 mL) was added and the temperature was kept below 40 C. After about 15 min, the mixture was cooled and then filtered. The filtrate was collected and acidified with 10% HCl, and extracted with ether (3×25 mL). The organic layer was dried (MgSO4), filtered, and concentrated under vacuum. Chromatography (10-30% EtOAc/hexanes) provided 9A10 (1 g, 37%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 7.0h; | To a stirred solution of 28 (25.0 g, 161 mmol) in DMF (500 mL) were added K2CO3 (6.80 g, 49.2 mmol) and MeI (11.0 mL, 177 mmol). After stirring for 7 h at room temperature, the reaction mixture was concentrated in vacuo and diluted with water. The resulting mixture was washed with EtOAc; the aqueous layer was acidified with 1 mol/L HCl and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (n-hexane-EtOAc = 2:1) to give 29 (8.78 g, 51.9 mmol, 32%) as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 3.95 (3H, s), 6.54 (1H, dd, J = 8.6, 1.2 Hz), 6.71 (1H, dd, J = 8.6, 1.2 Hz), 7.40 (1H, t, J = 8.6 Hz), 10.22 (1H, s). |
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 7.0h; | 3-Methoxy-2-nitrophenol To a solution of 2-nitroresoreinol (25.0 g) in DMF (500 mL) were added potassium carbonate (6.8 g) and methyl iodide (11.0 mL), followed by stirring at room temperature for 7 hours. The solvent was evaporated under reduced pressure, and then to the residue was added water, followed by washing with ethyl acetate. The aqueous layer was acidified with hydrochloric acid and extracted with ethyl acetate. The extracted layer was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to obtain the desired product (8.78 g) as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 3.95 (3H, s), 6.54 (1H, dd, J=8.6, 1.2 Hz), 6.71 (1H, dd, J=8.6, 1.2 Hz), 7.40 (1H, t, J=8.6 Hz), 10.22 (1H, s). | |
1.6 g | With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 0.5h; | 5 g of 2-nitrobenzene-1,3-diol was dissolved in N,N-dimethylformamide (75 mL), and then potassium carbonate (1.3 g, 0.3 equivalent) and methyl iodide (2.23 mL, 1.1 equivalents) were added thereto at 0 C., followed by stirring at room temperature for 30 minutes. The formation of the product was confirmed by TLC, and then distilled water was added to stop the reaction, followed by extraction using ethyl acetate. The organic phase was washed by 2 M hydrochloric acid (20 mL) and then dried over anhydrous magnesium sulfate, followed by filtration, and thus obtaining 1.6 g of the title compound by purification of the residue obtained by vacuum concentration of the filtrate through silica gel column chromatography (hexane:ethyl acetate=85:15).MS (ESI) m/z: 168 (M-H)- |
1.6 g | In N,N-dimethyl-formamide; at 0 - 20℃; for 0.5h; | 5 g of 2-nitrobenzene-1,3-diol was dissolved in N,N-dimethylformamide (75 mL), and then potassium carbonate(1.3 g, 0.3 equivalent) and methyl iodide (2.23 mL, 1.1 equivalents) were added thereto at 0C, followed by stirring atroom temperature for 30 minutes. The formation of the product was confirmed by TLC, and then distilled water wasadded to stop the reaction, followed by extraction using ethyl acetate. The organic phase was washed by 2 M hydrochloricacid (20 mL) and then dried over anhydrous magnesium sulfate, followed by filtration, and thus obtaining 1.6 g of thetitle compound by purification of the residue obtained by vacuum concentration of the filtrate through silica gel columnchromatography (hexane:ethyl acetate = 85:15).MS (ESI) m/z: 168 (M-H)- |