Structure of 110860-92-9
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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. : | 110860-92-9 |
Formula : | C5H3Cl2NO |
M.W : | 163.99 |
SMILES Code : | OC1=CN=C(Cl)C(Cl)=C1 |
MDL No. : | MFCD09835219 |
InChI Key : | GMHPKIGFTDRQBP-UHFFFAOYSA-N |
Pubchem ID : | 14391672 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 36.28 |
TPSA ? Topological Polar Surface Area: Calculated from |
33.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.42 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.13 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.09 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.02 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.23 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.78 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.69 |
Solubility | 0.333 mg/ml ; 0.00203 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.46 |
Solubility | 0.573 mg/ml ; 0.00349 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.67 |
Solubility | 0.348 mg/ml ; 0.00212 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 |
-5.79 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 |
1.0 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) |
1.65 |
* 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 sodium nitrite; In sulfuric acid; water; toluene; | EXAMPLE 11 5,6-dichloro-3-pyridinol Process (a) 8.15 g (50 mmol) of <strong>[98121-41-6]3-amino-5,6-dichloropyridine</strong> were dissolved in 100 ml of 8N H2 SO4 and diazotized at 0 C. using 3.55 g (53 mmol) of sodium nitrite in 9 ml of water. The cold diazonium salt solution was added dropwise to 100 C. warm 60% strength sulfuric acid. After completion of the nitrogen elimination, the mixture was neutralized and extractively distilled using toluene. The dried toluene phase was concentrated by evaporation and the residue was recrystallized repeatedly from toluene. Melting point 184-185 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | With triphenylphosphine; diethylazodicarboxylate; | 109b. 5,6-Dichloro-3-(1-t-butyloxycarbonyl-2-(S)-azetidinylmethoxy)pyridine N-Boc-2-(S)-azetidinol from Example 7b (1.55 g, 8.28 mmol), triphenylphosphine (2.6 g, 9.94 mmol), DEAD (1.6 mL, 9.94 mmol), and 5,6-dichloro-3-hydroxypyridine (1.5 g, 9.10 mmol) were allowed to react as in Example 9. The crude product was chromatographed eluding with EtOAc:hexane (1:5) to give 1.08 g of a waxy solid, 39% yield. MS (CI) m/e 333 (M+H)+. 1 H NMR (CDCl3, 300 MHz) d 7.97 (d, J=2.8 Hz, 1H), 7.41 (d, J=2.8 Hz, 1H), 4.56-4.48 (m, 1H), 4.40-4.30 (m, 1H), 4.12 (dd, J=10.1, 2.7 Hz, 1H-), 3.95-3.82 (m, 2H), 2.42-2.22 (m, 2H), 1.42 (s, 9H). |
39% | With triphenylphosphine; diethylazodicarboxylate; | 109b. 5,6-Dichloro-3-(1-t-butyloxycarbonyl-2-(S)-azetidinylmethoxy)pyridine N-Boc-2-(S)-azetidinol from Example 7b (1.55 g, 8.28 mmol), triphenylphosphine (2.6 g, 9.94 mmol), DEAD (1.6 mL, 9.94 mmol), and 5,6-dichloro-3-hydroxypyridine (1.5 g, 9.10 mmol) were allowed to react as in Example 9. The crude product was chromatographed eluding with EtOAc:hexane (1:5) to give 1.08 g of a waxy solid, 39% yield. MS (CI) m/e 333 (M+H)+. 1 H NMR (CDCl3, 300 MHz) δ: 7.97 (d, J=2.8 Hz, 1H), 7.41 (d, J=2.8 Hz, 1H), 4.56-4.48 (m, 1H), 4.40-4.30 (m, 1H), 4.12 (dd, J=10.1, 2.7 Hz, 1H), 3.95-3.82 (m, 2H), 2.42-2.2 (m, 2H), 1.42 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 6h; | A mixture of 5,6-dichloropyridin-3-ol (PREPARATION 15, 3.28 g, 20.0 mmol), <strong>[1354961-13-9]tert-butyl 5-chloro-2,4-difluorobenzoate</strong> (PREPARATION WO 2012007883, 4.96 g, 20.0 mmol) and potassium carbonate (4.15 g, 30.0 mmol) in anhydrous N,N-dimethylformamide (30 mL) was stirred at ambient temperature for 6 h followed by filtration. The residue was washed with ethyl acetate (100 mL). The filtrate was washed with saturated solution of ammonium chloride (3 x 20 mL), brine (3 x 20 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo and the residue was purified via silica gel column chromatography eluting with ethyl acetate in hexanes using 10-30% gradient to afford the title compound (0.51 g, 7% yield) as a colourless solid: NMR (300 MHz, CDC13) δ 8.09 (d, J= 2.7 Hz, 1H), 8.00 (d, J= 7.3 Hz, 1H), 7.41 (d, J= 2.7 Hz, 1H), 6.74 (d, J= 10.4 Hz, 1H), 1.58 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine; In tetrahydrofuran; dichloromethane; | 15a. 5-((2S)-azetidinylmethoxy)-2,3-dichloropyridine hydrochloride A solution of triphenylphosphine (2.6 g, 9.94 mmol) and diethyl azodicarboxylate (1.6 mL, 9.94 mmol) in THF (16 mL) was stirred at 0 C. for 15 minutes. 1-t-Butyloxycarbonyl-2-(S)-azetidinemethanol (1.55 g, 8.28 mmol, from step 7c above) and 5,6-dichloro-3-pyridinol (1.5 g, 9.1 mmol) were then added. The reaction mixture was allowed to warm slowly to room temperature and stir overnight. The solvent was removed, and the residue was redissolved in methylene chloride. The solution was washed with saturated aqueous K2 CO3 and brine, dried over MgSO4 and concentrated. The residue was chromatographed (silica gel; ethyl acetate:hexane, 1:5) to afford the 5,6-dichloro-3-(1-t-butyloxycarbonyl-2-(S)-azetidinylmethoxy)pyridine (1.08 g): MS (CI/NH3) m/z 333 (M+H)+; 1 H NMR (CDCl3, 300 MHz) δ 1.42 (s, 9H), 2.22-2.42 (m, 2H), 3.85-3.92 (m, 2H), 4.12 (dd, J=2.7, 10.1 Hz, 1 H), 4.30-4.40 (m, 1 H), 4.48-4.56 (m, 1 H), 7.41 (d, J=2.8 Hz, 1 H), 7.97 (d, J=2.8 Hz, 1 H). |
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