Structure of 188577-68-6
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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. : | 188577-68-6 |
Formula : | C5H4Cl2N2 |
M.W : | 163.01 |
SMILES Code : | NC1=NC=C(Cl)C(Cl)=C1 |
MDL No. : | MFCD07437842 |
InChI Key : | CRRAQLWJVYODCL-UHFFFAOYSA-N |
Pubchem ID : | 10773304 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 9 |
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 | 38.66 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.91 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.45 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.76 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.98 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.43 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.99 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.72 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.45 |
Solubility | 0.575 mg/ml ; 0.00353 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.19 |
Solubility | 1.04 mg/ml ; 0.00639 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.89 |
Solubility | 0.211 mg/ml ; 0.00129 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) |
No |
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 |
-6.04 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) |
1.57 |
* 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 |
---|---|---|
86% | With hydrogenchloride In water at 100℃; for 17 h; | A mixture of 4,5-dichloro-2-trimethylacetamido-pyridine (0.500 g, 2.02 mmol) and aqueous HCl (6N; 9.5 ml) was heated was heated at 100° C. for 17 h. The reaction mixture was allowed to cool to room temperature, diluted with ice-water (15 ml), and the pH of the mixture was adjusted to 7.0 with 10percent aqueous NaOH. The white precipitate was collected by filtration, washed with water (2.x.5 ml), and dried in vacuo over P2O5. The title compound was obtained as a white solid (0.284 g, 86percent); 1H-NMR (500 Mz, DMSO-d6) 6.44 (s, 2H, NH2, exchangeable with D2O), 6.64 (s, 1H), and 8.03 (s, 1H) (3-H, 6-H); LC-MS (ESI, m/z) 4.37 min-163, 165, 167 [(M+H)+, Cl2 isotopic pattern]. |
85% | With hydrogenchloride In water at 100℃; for 10 h; | A mixture of N-(4,5-dichloropyridin-2-yl)pivalamide (1.25 g, 5.04 mmol) in 6N HCl (20 mL) was stirred at 100° C. for 10 h. The mixture was cooled, combined with water (20 mL), and basified by the addition of sodium bicarbonate solution (20 mL). The mixture was extracted with ethyl acetate (3×40 mL), and the combined organic layers were dried over sodium sulfate, then evaporated under reduced pressure and purified by gradient column chromatography using ethyl acetate in n-hexane as eluent to afford 4,5-dichloropyridin-2-amine as a white solid (0.7 g, 85percent). 1HNMR (400 MHz, CDCl3): δ 8.06 (s, 1H), 6.60 (s, 1H), 4.48 (br s, 2H). LC-MS calcd exact mass 161.98, found m/z 162.8 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With N-chloro-succinimide In N,N-dimethyl-formamide at -20 - 20℃; for 24 h; | 5.2.2.30 7,8-Dichloro-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione (30) To a solution of 2-amino-4-chloropyridine (1.28 g, 10.0 mmol) in DMF (40 mL) at -20 °C was added NCS (2.67 g, 20.0 mmol). This mixture was allowed to warm to room temperature and stirred for 24 h, and then poured into 300 mL ice-water and extracted with ethyl acetate. The extracts were washed with 1 M NaOH and brine, dried and evaporated. The residue was purified by column chromatography on silica gel to give 4,5-dichloropyridin-2-amine (1.12 g, 69.0percent). |
66% | With N-chloro-succinimide In ethyl acetate at 20℃; for 28 h; | INTERMEDIATE 1 4,5-Dichloropyridin-2-amine To a solution of 4-chloropyridine-2-amine (50.00 g, 0.389 mol) in EtOAc (400 mL) was added N-chloro succinimide (53.50 g, 0.401 mol) in one portion. The mixture was stirred over night (28 h) at room temperature, and was then filtered to remove precipitated succinimide. The filtrate was washed with aqueous 0.5M NaOH (8x50 mL), water (2x50 mL) and brine (2x50 mL). The organic phase was dried (Na2S04), filtered and evaporated to furnish 59.4 g of crude light brown powder after vacuum drying. The dry isolated crude (with a purity of ca. 75percent of the title compound) was slurried in hexane (800 mL) and stirred at reflux temperature for 15 min. The mixture was allowed to cool to 35 °C and was then filtered using a G3 glass frit filter. The filter cake was washed with hexane (ca. 200 mL) and dried on the filter to furnish 42.1 g (66percent>) of brown solid. The product was pure enough (96percent>) to be taken to the next step. 1H NMR (600 MHz, DMSO-d6) δ ppm 8.02 (s, 1 H) 6.65 (s, 1 H) 6.42 (s, 2 H). MS: (ESI+) m z 163, 165, 167 [M+H]+, di-chlorine isotopic pattern. |
66% | With N-chloro-succinimide In ethyl acetate at 20℃; for 28 h; | To a solution of 4-chloropyridine-2-amine (50.00 g, 0.389 mol) in EtOAc (400 mL) was added N-chloro succinimide (53.50 g, 0.401 mol) in one portion. The mixture was stirred over night (28 h) at room temperature, and was then filtered to remove precipitated succinimide. The filtrate was washed with aqueous 0.5M NaOH (8x50 mL), water (2x50 mL) and brine (2x50 mL). The organic phase was dried (Na2SO4), filtered and evaporated to furnish 59.4 g of crude light brown powder after vacuum drying. The dry isolated crude (with a purity of ca. 75percent of the title compound) was slurried in hexane (800 mL) and stirred at reflux temperature for 15 min. The mixture was allowed to cool to 35 C and was then filtered using a G3 glass frit filter. The filter cake was washed with hexane (ca.200 mL) and dried on the filter to furnish 42.1 g (66percent) of brown solid. The product was pure enough (96percent) to be taken to the next step.1H NMR (600 MHz, DMSO-d6) δ ppm 8.02 (s, 1 H) 6.65 (s, 1 H) 6.42 (s, 2 H). MS: (ESI+) m/z 163, 165, 167 [M+H]+ , di-chlorine isotopic pattern. |
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