Structure of 1178884-53-1
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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. : | 1178884-53-1 |
Formula : | C5H4BrClN2O |
M.W : | 223.46 |
SMILES Code : | O=C1C(Br)=CC(Cl)=NN1C |
MDL No. : | MFCD21364605 |
InChI Key : | HXCPMIRSWJJTGV-UHFFFAOYSA-N |
Pubchem ID : | 59216474 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 42.47 |
TPSA ? Topological Polar Surface Area: Calculated from |
34.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.82 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.42 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.2 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.58 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.81 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.57 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.56 |
Solubility | 0.61 mg/ml ; 0.00273 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.76 |
Solubility | 3.91 mg/ml ; 0.0175 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.6 |
Solubility | 0.565 mg/ml ; 0.00253 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 |
-6.65 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 |
0.55 |
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) |
1.9 |
* 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 |
---|---|---|
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; | 6-Chloro-4-(5-methanesulfonyl-pyridin-2-ylamino)-2-methyl-2H-pyridazin-3-one 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (1 g, 4.48 mmol, Eq: 1.00), <strong>[35196-11-3]5-(methylsulfonyl)pyridin-2-amine</strong> (771 mg, 4.48 mmol, Eq: 1), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (388 mg, 671 μmol, Eq: 0.15) and cesium carbonate (5.1 g, 15.7 mmol, Eq: 3.5) were suspended in dioxane (80.0 ml). Finally tris (dibenzylideneacetone)dipalladium(0) (307 mg, 336 μmol, Eq: 0.075) was added. The reaction mixture was heated to 90 C. over night. Reaction mixture was filtered over celite; washed with dioxane; concentrated. Crude material was triturated with dichloromethane and precipitate was collected by filtration to afford an off-white solid (70 mg, 222 μmol) 1H NMR (300 MHz, DMSO-d6) δ ppm 3.25 (s, 3H) 3.69 (s, 3H) 7.73 (d, J=8.69 Hz, 1H) 8.16 (dd, J=1.00 Hz, 1H) 8.42 (s, 1H) 8.83 (d, J=2.27 Hz, 1H) | |
5.05 g | In a round-bottom flask under argon was placed 1.14 g 95% sodium hydride in oil dispersion and 90 mL of tetrahydrofuran (Aldrich, anhydrous, no inhibitor). The mixture was cooled in an ice bath and 3.10 g <strong>[35196-11-3]5-(methylsulfonyl)pyridin-2-amine</strong> was added one portion. The cooling bath was removed and the mixture stirred at room temperature. After 15 minutes the mixture was cooled in an ice bath and 4.103 g of 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one was added in one portion. The cooling bath was removed and the mixture stirred at room temperature. After 90 minutes, the mixture was cooled in an ice bath and quenched by the dropwise addition of 90 mL of 0.5 M hydrochloric acid (gas evolution at first few drops, color change from red brown to light tan, 15 minute addition). The cooling bath was removed, the mixture stirred for an additional 15 minutes and the solid collected by suction filtration, washing with water, then ether. The solid was air dried overnight to afford the desired product (5.05 g) as a light yellow solid. H NMR (300 MHz, DMSO-d6) δ ppm 3.25 (s, 3 H) 3.69 (s, 3 H) 7.73 (d, J=8.69 Hz, 1 H) 8.16(dd, J=1.00 Hz, 1 H) 8.42 (s, 1 H) 8.83 (d, J=2.27 Hz, 1 H). |
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