Structure of 1448-87-9
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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. : | 1448-87-9 |
Formula : | C8H5ClN2 |
M.W : | 164.59 |
SMILES Code : | ClC1=NC2=CC=CC=C2N=C1 |
MDL No. : | MFCD00043907 |
InChI Key : | BYHVGQHIAFURIL-UHFFFAOYSA-N |
Pubchem ID : | 238938 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 44.55 |
TPSA ? Topological Polar Surface Area: Calculated from |
25.78 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.9 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.23 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.28 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.45 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.62 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.1 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.94 |
Solubility | 0.19 mg/ml ; 0.00115 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.41 |
Solubility | 0.645 mg/ml ; 0.00392 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.94 |
Solubility | 0.0191 mg/ml ; 0.000116 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 |
-5.72 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 |
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) |
1.69 |
* 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 |
---|---|---|
77% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 24h; | General procedure: 2-Phenylquinoxaline (pqx) was prepared from a reaction of 2-chloroquinoxaline and phenylboronic acid. 2-Chloroquinoxaline(3.00 g, 18.2 mmol), phenylboronic acid (2.44 g,20.0 mmol) and tetrakis(triphenylphosphine)palladium(0)(0.98 g, 0.85 mmol) were added to 50 mL of THF. After adding 5 mL of aqueous 4 M K2CO3, the reaction mixture was heated to 80 C for 24 h. The cooled crude mixture was poured into water, extracted with CH2Cl2 (50 mL × 3 times)and dried over anhydrous magnesium sulfate. Finally, silica column purification (n-hexane:EtOAc = 5:1) gave 3.15 g of a white solid in quantitative yield (84%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; lithium hydroxide; In 1,4-dioxane; water; at 80℃; for 0.5h;Inert atmosphere; | General procedure: To a solution of 2-chloroheteroaryl compound 1 (0.50 mmol) in 1,4-dioxane (4.0 mL) were added pinacol boronate 3, 5, or 7 (0.60 mmol), Pd(OAc)2 (1.1 mg, 5.0 mumol), S-Phos (4.1 mg, 10.0 mumol), and 2 M LiOH solution (1.0 mL, 2.0 mmol) at room temperature, and the mixture was stirred for 30 min at 80 C under N2 atmosphere. The reaction was quenched by adding water, and then the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was removed in vacuo, and the residue was purified by silica-gel column chromatography. The solvent was removed in vacuo, and the residue was triturated with Et2O to give biaryl compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 160℃; for 0.5h;Microwave irradiation; | General procedure: A mixture of the corresponding bromo-substituted 1,4-diazine (1.0mmol), arylboronic derivative (2 or 4) (1.2mmol), Pd(PPh3)4 (58mg, 5mol %) and K3PO4 (530mg, 2.5mmol) was dissolved in 1,4-dioxane 15mL. The reaction mixture was degassed and irradiated in a microwave apparatus at 160 C (250 W) for 30min. The reaction mixture was cooled, filtered, and dissolved in a mixture of EtOAc and water (1:1, 50mL), and the organic layer was separated. The aqueous layer was extracted with EtOAc (2×25mL). The combined organic extracts were dried with MgSO4 and the solvents evaporated. Purification by silica gel column chromatography with EtOAc/hexane (1:4, v/v) as an eluent to afford the desired cross-coupling products. |
73% | With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 160℃; for 0.5h;Microwave irradiation; | General procedure: A mixture of the correspondingchloro-substituted (1 or 2) [or bromo-substituted (3 or 4)] 1,4-diazine(1.0 mmol), arylboronic derivative (5b or 5c) (1.2 mmol), Pd(PPh3)4 (58 mg, 5 mol %) and K3PO4 (530 mg, 2.5 mmol) was dissolved in 1,4-dioxane 15 mL. The reaction mixture was degassed and irradiated in a microwave apparatus at 160 C (250 W) for 30 min. The reaction mixture was cooled, filtered, and dissolved in a mixture of EtOAc and water (1:1, 50 mL), and the organic layer was separated. The aqueous layer was extracted with EtOAc (2 × 25 mL). The combined organic extracts were dried with MgSO4 and the solvents evaporated. Purification by silica gel column chromatography with EtOAc/hexane (1:4, v/v)as an eluent to afford the desired cross-coupling products. |