Structure of 124691-76-5
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 124691-76-5 |
Formula : | C7H4Cl2N2 |
M.W : | 187.03 |
SMILES Code : | ClC1=CC2=C(C=C1Cl)C=NN2 |
MDL No. : | MFCD11878111 |
InChI Key : | MCHJBZZQBWIBOK-UHFFFAOYSA-N |
Pubchem ID : | 412303 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 46.11 |
TPSA ? Topological Polar Surface Area: Calculated from |
28.68 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 |
2.81 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.87 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.31 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.31 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.53 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.38 |
Solubility | 0.0788 mg/ml ; 0.000421 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.07 |
Solubility | 0.159 mg/ml ; 0.000852 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.14 |
Solubility | 0.0134 mg/ml ; 0.0000718 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
-5.45 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) |
1.56 |
* 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 |
---|---|---|
84% | Step 25 ,6-Dichloro-l H-indazolTo a solution of 4,5-dichloro-2-methylaniline (1.69 g, 9.6 mmol) in CHC13 (25 ml) at 0C was slowly added acetic anhydride (2.09 ml, 22.1 mmol). The reaction mixture was warmed to room temperature and stirred for 1 h. A thick white precipitate had gradually formed. Potassium acetate (283 mg, 2.88 mmol) was added followed by slow addition of isoamyl nitrite (2.78 ml, 20.6 mmol). The reaction mixture was heated at reflux overnight. The homogeneous deep orange reaction mixture was cooled to room temperature and concentrated. Water (10 mL) was added and the mixture was reconcentrated to an orange solid. This solid was suspended in cone. HCl (15 mL) and heated at 60C for 2 h then cooled to 0C and neutralized with 50% NaOH. Extracted with EtOAc, dried over MgS04 and concentrated to an orange solid. This solid was dissolved in THF/MeOH (1 :1 , 25 mL) and 10%> NaOH (3 mL) was added. The deep maroon reaction mixture was stirred at room temperature for 5 min then neutralized with 1.0 M HCl and diluted with water. The mixture was extracted with EtOAc (2 x) then dried over MgS04 and concentrated. The residue was absorbed onto silica gel and purified by chromatography with 30% to 50% EtOAc/hexanes to afford 1.50 g (84%) of 5, 6-dichloro-l H-indazole as a light orange solid. 1H NMR (CDC13, 300 MHz): ? (ppm) 8.04 (s, 1H), 7.89 (s, 1H), 7.68 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; potassium phosphate; copper(l) iodide; In toluene; at 110℃; for 48.0h;Inert atmosphere; Microwave irradiation; Sealed tube; | Step 22 -(5 ,6 -Dichloro -indazo 1- 1carboxylic acid [(R)-2-(4-cyano-piperidin-l-yl)-l-cyclopropyl-2-oxo-ethyl]-amideIn a 5 mL microwave vial were placed copper(I) iodide (6 mg, 0.033 mmol), K3PO4 (146 mg, 0.69 mmol), 5,6-dichloro-lH-indazole (74 mg, 0.39 mmol), 2-iodo-5-(2-trimethylsilanyl- ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-l -yl)-l - cyclopropyl-2-oxo-ethyl]-amide (200 mg, 0.33 mmol), toluene (1.2 mL), and trans-N,N'- dimethylcyclohexane-l ,2-diamine (9 mg, 0.066 mmol). The vial was purged with a stream of nitrogen then sealed and heated in an oil bath at 110C for 48 h. The reaction mixture was cooled to room temperature and diluted with EtOAc then filtered over a Buchner funnel, rinsing with EtOAc. The filtrate was concentrated and the resultant residue was purified by silica gel chromatography with 0% to 2% MeOH/CH2Cl2 (0.5% NH4OH) to afford 215 mg (98%) of 2- (5 ,6 -dichloro -indazo 1- 1 -yl)-5 -(2 -trimethylsilanyl-ethoxymethyl)-5 H-pyrro lo [2 ,3 -b ]pyrazine-7 - carboxylic acid [(R)-2-(4-cyano-piperidin-l-yl)-l-cyclopropyl-2-oxo-ethyl]-amide as a light yellow foam. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 0.75h; | Step 35 ,6 -Dichloro -3 -iodo - 1 H-indazo leTo a solution of 5, 6-dichloro-l H-indazole (0.50 g, 2.67 mmol) in DMF (8 ml) at room temperature was added powdered potassium hydroxide (450 mg, 8.02 mmol) and iodine (1.02 g, 4.01 mmol). The maroon reaction mixture was stirred at room temperature for 45 min then quenched with 10%> aqueous Na2S203 and diluted with water. The mixture was extracted with EtOAc (2x). The combined organics were washed with water (3x), dried over MgS04 and concentrated to afford 827 mg (99%) of 5,6-dichloro-3-iodo-lH-indazole as a pale yellow solid. 'H NMR (DMSO-dg, 400 MHz): ? (ppm) 13.79 (s, 1H), 7.94 (s, 1H), 7.72 (s, 1H). |