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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
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Inaccessible (Haz class 6.1), Domestic | USD 80+ |
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Structure of 5460-31-1
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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.
4.5
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CAS No. : | 5460-31-1 |
Formula : | C7H7NO3 |
M.W : | 153.14 |
SMILES Code : | OC1=CC=CC([N+]([O-])=O)=C1C |
MDL No. : | MFCD00007241 |
InChI Key : | GAKLFAZBKQGUBO-UHFFFAOYSA-N |
Pubchem ID : | 79579 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H301-H315-H319-H412 |
Precautionary Statements: | P501-P273-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330 |
Class: | 6.1 |
UN#: | 2446 |
Packing Group: | Ⅲ |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 42.25 |
TPSA ? Topological Polar Surface Area: Calculated from |
66.05 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.36 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.11 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.61 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.61 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.36 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.46 |
Solubility | 0.535 mg/ml ; 0.0035 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.13 |
Solubility | 0.114 mg/ml ; 0.000745 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.57 |
Solubility | 4.08 mg/ml ; 0.0267 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 |
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 |
-5.74 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) |
1.64 |
* 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 |
---|---|---|
Intermediate 57To a solution of 2-methyl-3-nitrophenol (15.3 g, 100 mmol) in DMF (150 mL) was added sodium hydride (60% in mineral oil, 2.6 g, 1 10 mmol) at 0C and the mixture was stirred for 30 minutes at room temperature. Methyl iodide (28.4 g, 200 mmol) was added and the mixture was heated to 80 C for 5 hours. Water (100 mL) was added and the mixture was extracted with ethyl acetate (3 times 100 mL). The combined ethyl acetate phases were dried over sodium sulphate and concentrated under vacuum to give a residue, which was purified by column chromatography on silica gel (PE:EtOAc = 5: 1 ). Evaporation afforded the title compound as a yellow solid (14.4 g). | ||
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 14.0h; | Methyl iodide (8.13 mL, 130.6 mmol) was added dropwise to a solution of 8 (10 g, 65.29 mmol) ,and potassium carbonate (18.05 g, 130.6 mmol) in anhydrous DMF (130 mL). The reaction mixture was stirred at rt for 14 h and quenched by the addition of H2O (250 mL). The aqueous phase was extracted with EtOAc (3 × 200 mL), the combined organic layers washed with water (100 mL), saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated to give corresponding methyl ether as a colorless solid. Palladium on carbon (10%, 200 mg) was added to a solution of above product in EtOAc (130 mL). The suspension was stirred at rt for 6 h under a hydrogen atmosphere before it was filtered through a plug of celite and eluted with EtOAc (150 mL). The eluent was concentrated to afford 12 (8.59 g, 96% over two steps) as a colorless amorphous solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-chloro-succinimide; sulfuric acid; sodium sulfate; sodium nitrite; In water; acetonitrile; | 4. Preparation of 4-chloro-2-methyl-3-nitrophenol A slurry of 4-chloro-2-methyl-3-nitroaniline (20.9 g), water (200 mL), and fluroboric acid (86 mL) was heated to boiling until almost complete solution took place, then cooled to 0-5 C. A solution of sodium nitrite (8.11 g) in water (20 mL) was then added dropwise to the above mixture, and then the mixture was stirred in the cold for an additional 30 min. The precipitated diazonium salt was filterd off and washed with a little cold water. The wet diazonium salt was added all at once to a hot (100-120 C.) solution of water (230 mL), concentrated sulfuric acid (115 mL), and sodium sulfate (35 g), and allowed to stir for 4 hr. The reaction mixture was cooled to room temperature and extracted with ethyl ether (700 mL in two portions). The combined ether extracts were washed with saturated sodium chloride solution, then dried over magnesium sulfate. Evaporation afforded crude product (17.5 g), which was purified by flash chromatography on silica, eluding with methylene chloride to afford 7.6 g as a yellow solid. The phenol was also prepared by the NCS chlorination of 2-methyl-3-nitrophenol, in a manner similar to that described in Oberhauser, J. Org. Chem. (1997) 62:4504-4506, as follows. STR72 2-Methyl-3-nitrophenol (25.5 g), N-chlorosuccinimide (44.5 g), and trifluormethanesulfonic acid (50.0 g) were combined in dry acetonitrile (500 mL) and allowed to stir under an atmosphere of nitrogen at 75 C. for 1.5 hr. The reaction mixture was cooled to room temperature, diluted with ethyl ether (650 mL), washed with water, 10% sodium bisulfite solution, water, and finally saturated sodium chloride solution. Evaporation of the solvent afforded a crude material which was flash chromatographed on silica and eluted with acetone:hexane (1:9) to afford 16.8 g as a yellow solid. | |
With N-chloro-succinimide; sulfuric acid; sodium sulfate; sodium nitrite; In water; acetonitrile; | 4. Preparation of 4-chloro-2-methyl-3-nitrophenol A slurry of 4-chloro-2-methyl-3-nitroaniline (20.9 g), water (200 mL), and fluroboric acid (86 mL) was heated to boiling until almost complete solution took place, then cooled to 0-5C. A solution of sodium nitrite (8.11 g) in water (20 mL) was then added dropwise to the above mixture, and then the mixture was stirred in the cold for an additional 30 min. The precipitated diazonium salt was filterd off and washed with a little cold water. The wet diazonium salt was added all at once to a hot (100-120C) solution of water (230 mL), concentrated sulfuric acid (115 mL), and sodium sulfate (35 g), and allowed to stir for 4 hr. The reaction mixture was cooled to room temperature and extracted with ethyl ether (700 mL in two portions). The combined ether extracts were washed with saturated sodium chloride solution, then dried over magnesium sulfate. Evaporation afforded crude product (17.5 g), which was purified by flash chromatography on silica, eluding with methylene chloride to afford 7.6 g as a yellow solid. The phenol was also prepared by the NCS chlorination of 2-methyl-3-nitrophenol, in a manner similar to that described in Oberhauser, J. Org. Chem . (1997) 62 :4504-4506, as follows. 2-Methyl-3-nitrophenol (25.5 g), N-chlorosuccinimide (44.5 g), and trifluormethanesulfonic acid (50.0 g) were combined in dry acetonitrile (500 mL) and allowed to stir under an atmosphere of nitrogen at 75 C for 1.5 hr. The reaction mixture was cooled to room temperature, diluted with ethyl ether (650 mL), washed with water, 10% sodium bisulfite solution, water, and finally saturated sodium chloride solution. Evaporation of the solvent afforded a crude material which was flash chromatographed on silica and eluted with acetone:hexane (1:9) to afford 16.8 g as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With 2-(Dimethylamino)pyridine; acetic anhydride; triethylamine;palladium-carbon; In ethyl acetate; | EXAMPLE 2 Synthesis of 4-acetoxyindole A suspension of 3.24 g of trans-6-benzyloxy-2-nitro-beta-pyrrolindino -styrene (prepared from 2-methyl-3-nitrophenol by a procedure reported in Organic Synthesis, Coll. Vol. 7, 34, 1990) and 648 mg of 10% pd/C catalyst in 30 ml of ethyl acetate was shaken under hydrogen atmosphere and at 50 psi, for 5 hours. To this reaction mixture were added acetic anhydride (1.4 ml), triethylamine (2.1 ml) and dimethylaminopyridine (324 mg). The resultant mixture was stirred for 1 hour at room temperature. The catalyst was removed over a layer of Celite and the filtrate was evaporated under reduced pressure to give an oily residue to which crushed ice was added. The resulting white precipitate was collected by filtration to give 1.2 g (69% yield) of 4-acetoxyindole: mp 97-98 C.; H-NMR (300 MHz, DMSO-d6)delta 2.32 (s,3H), 6.31 (s,1H), 6.71 (d,1H,J=8Hz), 7.05 (t, 1H, J=8 Hz), 7.28 (d,1H,J=8Hz), 7.32 (s,1H), 11.27 (s,1H). |
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