Structure of 60186-16-5
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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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CAS No. : | 60186-16-5 |
Formula : | C5H2ClFN2O2 |
M.W : | 176.53 |
SMILES Code : | [O-][N+](=O)C1=CC(Cl)=CN=C1F |
MDL No. : | MFCD06659522 |
InChI Key : | QYRFYYRMUFOIKW-UHFFFAOYSA-N |
Pubchem ID : | 12275768 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 38.03 |
TPSA ? Topological Polar Surface Area: Calculated from |
58.71 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.07 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.74 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.2 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.12 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.37 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.3 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.37 |
Solubility | 0.756 mg/ml ; 0.00428 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.59 |
Solubility | 0.454 mg/ml ; 0.00257 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.3 |
Solubility | 0.887 mg/ml ; 0.00502 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 |
-6.14 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 |
3.0 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) |
2.01 |
* 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 |
---|---|---|
aluminum nickel; In ethanol; hexane; ethyl acetate; | Example P10 3-Amino-5-chloro-2-fluoropyridine 7.5 g (0.042 mol) of <strong>[60186-16-5]5-chloro-2-fluoro-3-nitropyridine</strong> are dissolved in 80 ml of ethanol. This solution is hydrogenated with hydrogen, in the presence of 1 g of Raney nickel catalyst, under normal pressure and at a temperature in the range from 20 to 25 C. After a hydrogenation period of 20 hours, the catalyst is removed and the solvent is evaporated off. The residue is taken up in ethyl acetate and the resultant solution is filtered through a layer of silica gel. The solvent is evaporated off and the residue is triturated in hexane. The precipitate is subsequently filtered and dried, affording 4.7 g (76%) of 3-amino-5-chloro-2-fluoropyridine, m.p. 74 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; at 0 - 20℃; for 6.16667h;Reflux; | 4-(5-Chloro-3-nitropyridin-2-yl)morpholine To a stirred solution of <strong>[60186-16-5]5-chloro-2-fluoro-3-nitropyridine</strong> (5 g, 28 mmol) in THF (40 mL) was added morpholine (4 mL, 42 mmol). The reaction was stirred at 0 C. for ten min, at rt for 1 h, and refluxed for four h. The reaction was then cooled to rt, taken up in EtOAc, and washed with satd aq. sodium bicarbonate and brine. The organic layer was dried (magnesium sulfate) and concentrated, affording 4-(5-chloro-3-nitropyridin-2-yl)morpholine as a yellow oil. Mass Spectrum (ESI) m/e=244.0 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
520 mg | With 1-methyl-pyrrolidin-2-one; N-ethyl-N,N-diisopropylamine; In acetonitrile; for 3.0h;Reflux; | General procedure: A mixture of 2-chloro-4-phenylpyrimidine (71 mg, 0.37 mmol), Intermediate 20 (100 mg, 0.34 mmol) and DIPEA (120 muIota_, 0.68 mmol) in NMP (1 mL) was heated at 130C for 3 hrs. The reaction mixture was allowed to cool to ambient temperature and diluted with water (10 mL). The crude product was extracted into diethyl ether (20 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by chromatography on the Biotage Companion (12 g column, 0 to 100% diethyl ether in isohexane) to afford the title compound as a gum (65 mg). LCMS (Method A): Two peaks at 2.45 min and 2.66 min, 451 [M+H]+.1H NMR (400 MHz, DMSO-d6, 374 K) 8.36 (d, 0.8 H), 8.30 (bd, 0.2 H), 8.15-8.07 (m, 1 .6 H), 7.97 (bm, 0.3 H), 7.56-7.46 (m, 3.92 H), 7.46-7.24 (m, 7.38 H), 7.16-7.05 (m, 1.8 H), 6.33 (bs, 1 H), 4.41 (td, 1 H), 3.71 (m, 1 H), 3.50 (m, 1 .1 H), 3.26 (bm, 0.2 H), 2.84 (s, 0.3 H), 2.82 (s, 0.3 H), 2.63 (s, 0.3 H), 2.48 (s, 2.1 H), 1 .82 (bm, 0.7 H), 1.00 (d, 2.5 H), 0.78 (bd, 0.5 H), 0.56 (bs, 3 H). |
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