Structure of 500011-86-9
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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. : | 500011-86-9 |
Formula : | C9H5BrClN3O2 |
M.W : | 302.51 |
SMILES Code : | O=C(C1=CC(Br)=NN1C2=NC=CC=C2Cl)O |
MDL No. : | MFCD08689880 |
InChI Key : | FORBXGROTPOMEH-UHFFFAOYSA-N |
Pubchem ID : | 11587535 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 11 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 61.03 |
TPSA ? Topological Polar Surface Area: Calculated from |
68.01 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.76 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.67 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.38 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.85 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.66 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.06 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.77 |
Solubility | 0.0509 mg/ml ; 0.000168 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.75 |
Solubility | 0.0538 mg/ml ; 0.000178 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.38 |
Solubility | 0.125 mg/ml ; 0.000412 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 |
-6.25 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 |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.38 |
* 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 |
---|---|---|
Step 5: Preparation of N'- (3- { [5-bromo-2- (3-chloro-pyridin -2-yl) -2No.-pyrazole-3-carbonyl] -amino} -4 , 6-dichloro- pyridine-2-carbonyl) -hydrazinecarboxylic acid methyl ester; 5-Bromo-2- (3-chloro-pyridin-2-yl) -2H-pyrazole-3-carboxylic acid (example 1, step 5) (142 mg) was suspended in acetonitrile (1 ?iL) and pyridine (65 muL) and methanesulfonyl chloride (50 muL) were added. The reaction mixture was stirred for 30 min at room temperature, 3- amino-4 , 6-dichloro-pyridine-2-carboxylic acid (99 mg) in acetonitrile (1 mL) and pyridine (130 muL) were added and the reaction mixture was stirred 1 h at room temperature. Methanesulfonyl chloride (65 muL) was added and the reaction mixture was stirred for 20 h at room temperature. The reaction mixture was concentrated in vacuum, the residue was suspended in DMF (5 mL) , carbazaic acid methyl ester (216 mg) was added and the reaction mixture was stirred for 20 h at room temperature. Water was added and the mixture was 2x extracted with MTB-ether. The combined organic layer was washed 3x with water, washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, <n="460"/>hexane/ethyl acetate = 2:1, Rf = 0.15) to afford 37 mg of the compound 14 of the present invention of the formulaas a white solid. 1H-NMR (CDCl3, TMS) delta (ppm) : 3.82 (3H, s) , 6.66 (IH, br s) ,7.08 (IH, s), 7.39 (IH, dd, J = 8 Hz, ' 5 Hz) , 7.57 (IH, s) , 7.86 (IH, dd, J = 8 Hz, 2 Hz), 8.47 (IH, dd, J = 5 Hz, 2 Hz), 9.40 (IH, s), 10.71 (IH, s) . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57.3% | 0.72 g (2.4 mmol) of 3-bromo-1- (3-chloropyridin-2-yl) -5-pyrazolecarboxylic acid,0.46 g (2.4 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI), 0.32 g (2.4 mmol) of 1-hydroxybenzotriazole (HOBt), 10mL N, N-dimethylformamide (DMF), stirred at room temperature for 30min, then added 0.38g (2.0mmol) of 4-methyl-5-ethoxycarbonylthiazole-2-amine, 0.5mL of triethylamine, 120 C The reaction was stirred for 4.0h, and the solid was precipitated by pouring into water. The crude product was purified by column chromatography to obtain N-[(4-methyl-5-ethoxycarbonylthiazol-2-yl)]-3-bromo-1-(3-chloropyridin-2-yl)-5-pyrazolecarboxamide (Ia), mp 220-222 C, yield 57.3%; |
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