Structure of 21803-75-8
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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. : | 21803-75-8 |
Formula : | C7H5ClN2 |
M.W : | 152.58 |
SMILES Code : | C1=C(C#N)C=C(C(=C1)N)Cl |
MDL No. : | MFCD00052917 |
InChI Key : | OREVCMGFYSUYPX-UHFFFAOYSA-N |
Pubchem ID : | 519896 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 40.57 |
TPSA ? Topological Polar Surface Area: Calculated from |
49.81 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.46 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.0 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.8 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.39 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.72 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.67 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.49 |
Solubility | 0.494 mg/ml ; 0.00324 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.67 |
Solubility | 0.324 mg/ml ; 0.00213 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.72 |
Solubility | 0.289 mg/ml ; 0.00189 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) |
Yes |
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 |
-5.81 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) |
1.43 |
* 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 |
---|---|---|
74% | With sodium borate; In acetic acid; at 50 - 62℃; for 3h; | A suspension of sodium borate tetrahydrate (32.5 g, 211.2 mmol) in 195 ml of acetic acid was heated until the temperature of the reaction mixture was above 50 C. The reaction temperature was kept this way while 2-chloro-4-cyanoaniline (5.93 g, 38.9 mmol) was added in portions over 1 h. Stirring and heating were continued for 2 hours on an oil bath of 62 C. After cooling to room temperature the reaction mixture was poured into 1 L icewater. The aqueous layer was extracted with Et2O (3×). The combined organic layers were washed with H2O (2×) and dried (MgSO4). The drying agent was removed by filtration and the solvent by evaporation under reduced pressure. The residue was chromatographed (SiO2) with Et2O/petroleum ether 1/3 as eluent to give 5.27 g (74%) of the oxidized product. |
With sodium nitrite; In hydrogenchloride; water; | 1. 4-nitro-3-chlorobenzonitrile To an ice cold solution of 4-amino-3-chlorobenzonitrile (1 g, 6.6 mmol) in concentrated HCl (2.5 mL) plus water (2.5 mL) a chilled solution of sodium nitrite (0.74 g, 1.62 eq) in water (3.6 mL) is added dropwise to maintain the reaction temperature <0 C. After stirring at 0 C. for 10 min, the mixture is added portion-wise to an ice cold solution of sodium nitrite (3.29 g, 7.22 eq) and copper(I) oxide (349 mg, 0.37 eq) in water 14.5 mL). Stirring is continued at 0 C. for 40 min, and then at room temperature for 0.5 h. The reaction mixture is extracted with dichloromethane (2*), the combined organic layers washed with saturated aqueous sodium chloride, dried (MgSO4), concentrated, and purified by silica gel chromatography to give 4-nitro-3-chlorobenzonitrile. 1H NMR (CDCl3): delta 7.96 (d, J=8.24 Hz, 1 h), 7.88 (d, J=1.65 Hz, 1H), 7.63 (dd, J=1.65, 8.24 Hz, 1H. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium nitrite; In water; | 3-Chloro-4-nitro-benzonitrile Sodium nitrite (6.78 g in water (40 mL) at 0 C.) was slowly added to a solution of 4-amino-3-chloro-benzonitrile (10.5 g) in water (30 mL) and concentrated hydrochloric acid (30 mL) also at 0 C. After 10 minutes the solution was poured onto a suspension of cuprous oxide (3.48 g) and sodium nitrite (31.69 g) in water (100 mL) at 0 C. The ensuing mixture was stirred at 0 C. for 1 hour then at 23 C. for 1 hour. The resulting mixture was extracted with dichloromethane and the organic layer washed with saturated sodium chloride. The separated organic layer was dried over sodium sulfate and then concentrated to give 3-chloro-4-nitro-benzonitrile (11.31 g). |
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