Structure of 18583-89-6
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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. : | 18583-89-6 |
Formula : | C9H11NO2 |
M.W : | 165.19 |
SMILES Code : | O=C(OC)C1=CC=CC(N)=C1C |
MDL No. : | MFCD00211328 |
InChI Key : | ZOOQFAUFPWXUMI-UHFFFAOYSA-N |
Pubchem ID : | 3801025 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 47.09 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.32 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.77 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.46 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.37 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.64 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.44 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.54 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.02 |
Solubility | 1.57 mg/ml ; 0.00951 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.16 |
Solubility | 1.13 mg/ml ; 0.00684 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.49 |
Solubility | 0.531 mg/ml ; 0.00321 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 |
-6.27 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 |
1.0 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) |
1.32 |
* 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 |
---|---|---|
69% | With acetic acid; sodium nitrite; In water; | Methyl-3-amino-2-methyl benzoate (0.3 g, 1.96 mmol) was stirred in aqueous NaNO2 (0.62 g, 2 mmol) followed by addition of 7 mL dilute glacial acetic acid in water (7 mL, 3 mmol) (0.2:10). The reaction mixture was allowed to stir for 4-6 hrs. The mixture was then extracted with EtOAc and washed with water (2×10 mL). The organic layer was dried over Na2SO4, concentrated and subjected to column chromatography to obtain yellow powder. The yield was 0.22 g, 69%; m.p. 153-155 C. 1H NMR (400 MHz CDCl3, TMS, ppm) delta 2.55 (s, 3H), 7.37 (t, 1H, J=14.32 Hz), 7.53 (s, 1H), 7.67 (d, 1H, J=8.12 Hz), 7.82 (d, 1H, J=8.16 Hz), 9.79 (s, 1H). |
59% | Reference Example 1 methyl 1H-indazole-4-carboxylate A mixture of methyl 3-amino-o-toluate (100 g, 605 mmol), a solution of ammonium tetrafluoroborate (83.0 g, 787 mmol) in water (600 mL) and concentrated hydrochloric acid (121 mL, 3.93 mmol) was cooled to 0C, and a solution of sodium nitrite (41.8 g, 605 mmol) in water (88 mL) was added dropwise to the mixture over 25 min. This mixture was stirred for 35 min, and the resulting solid was collected by filtration. This solid was washed with water, methanol and diethyl ether, dried under nitrogen atmosphere, and added to a solution of potassium acetate (65.4 g, 666 mmol) and 18-crown-6 (4.50 g, 17.0 mmol) in chloroform (1.37 L). The resulting mixture was stirred at room temperature for 2 hr, and water (700 mL) was added. The partitioned organic layer was washed with water, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was triturated with hexane, and collected by filtration to give the title compound (63.0 g, yield 59%). 1H-NMR (CDCl3) delta: 4.03 (3H, s), 7.47 (1H, dd, 8.4, 7.2 Hz), 7.73 (1H, d, J = 8.4 Hz), 7.96 (1H, d, J = 7.2 Hz), 8.61 (1H, s), MS (ESI+): 177 (M+H). | |
Step 3: methyl 1 H-indazole-4-carboxylate; To a cold (0-5 C) solution of methyl-3-amino-2-methyl benzoate (16.6 mL, 19.0 g, 0.12 mol) in chloroform (200 mL) was added dropwise acetic anhydride (24.8 mL, 0.26 mol) followed by stirring for 5 minutes. The resulting mixture was allowed to warm to room temperature and stirred for 1 hour and then was added potassium acetate (3.35g, 0.034 mol) and isoamyl nitrite (33.0 mL, 0.25 mol) and heated under reflux for 20 hours. The mixture was cooled to room temperature and solvent was evaporated to yield a brown solid. Water was added to the solid, followed by evaporation to yield a solid residue. The residue was treated with concentrated hydrochloric acid and the resulting mixture was heated at 500C for 2 hours. After cooling with an ice bath, the solution was basified to pH 14 with a 50% potassium hydroxide solution. The resulting solid was collected by filtration, washed with water and dried to yield 17.8 g of methyl 1 H-indazole-4-carboxylate as a beige solid. MS: 177.0 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With chloro-trimethyl-silane; triethylamine; In pyridine; at 100℃; | Aniline (1.5 g, 9.1 mmol) was dissolved in pyridine (45 mL) and<strong>[628-36-4]diformylhydrazine</strong> (2.4 g, 27.2 mmol) was added as a single portion.Chlorotrimethylsilane (17.3 mL, 136.2 mmol) was added dropwise followed bytriethylamine (8.9 mL, 63.6 mmol) dropwise. The reaction as heated overnight to 100°C after which is was cooled to room temperature, diluted with EtOAc, washed with water, brine and dried over magnesium sulfate. Filtration and concentration was followed by silica gel chromatography (eluent: EtOAc / hexanes) to yield the product. |
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