Structure of 101623-69-2
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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. : | 101623-69-2 |
Formula : | C9H8ClNO5 |
M.W : | 245.62 |
SMILES Code : | O=C(OC(Cl)C)OC1=CC=C([N+]([O-])=O)C=C1 |
MDL No. : | MFCD19441847 |
InChI Key : | DXVQFTPXVZUWIF-UHFFFAOYSA-N |
Pubchem ID : | 10538354 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 57.84 |
TPSA ? Topological Polar Surface Area: Calculated from |
81.35 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.78 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.02 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.7 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.05 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.16 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.68 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.21 |
Solubility | 0.15 mg/ml ; 0.000612 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.39 |
Solubility | 0.00993 mg/ml ; 0.0000404 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.27 |
Solubility | 1.33 mg/ml ; 0.00543 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 |
No |
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) |
Yes |
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 |
-5.65 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 |
4.0 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) |
2.8 |
* 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 |
---|---|---|
97% | With pyridine In dichloromethane at 0 - 20℃; for 1.5 h; | To an ice cold reaction mixture containing p-nitrophenol (1.39 g, 10 mmol) and pyridine (0.81 g, 10 mmol) in dichloromethane (60 mL) was added 1-chloroethyl chloroformate (1.2 mL, 11 mmol). The mixture was stirred at 0° C. for 30 min and then at room temperature for 1 hour. After removing the solvent under reduced pressure, the residue was dissolved in ether, washed with water, 10percent citric acid and water. The ether layer was dried over Na2SO4 and evaporated under reduced pressure to give 2.4 g (97percent) of the title compound (57) as an off-white solid. 1H NMR (CDCl3): 1.93 (d, 3H), 6.55 (q, 1H), 7.42 (d, 2H), 8.28 (d, 2H). |
92% | With pyridine In dichloromethane at 0 - 20℃; for 6 h; | Example 3: 1-iodoethyl 4-nitrophenyl carbonateSTEP A: 1-chloroethyl 4-nitrophenyl carbonate.To a solution of 4-nitrophenol (3.0 g, 21.6 mmol) and pyridine (1.9 mL, 24 mmol) in CH2C12 (48 mL) cooled to 0°C, 1-chloroethyl chloroformate (2.3 mL, 21.6 mmol) was added. The reaction was stirred at room temperature for 5-6 hours, then washed with NaH2PC>4 (5percent) and brine, dried over Na2SC>4 and concentrated affording the title compound (4.88 g, 92percent) as a pale yellow solid. |
92% | at 0 - 20℃; | STEP A: 1-chloroethyl 4-nitrophenyl carbonateTo a solution of 4-nitrophenol (3.0 g, 21.6 mmol) and pyridine (1.9 mL, 24 mmol) cooled to 0°C, 1-chloroethyl chloroformate (2.3 mL, 21.6 mmol) was added. The reaction was stirred at room temperature for 5-6 hours, then washed with Na3/4P04 (5percent) and brine, dried over Na2 S C>4 and concentrated affording the title compound (4.88 g, 92percent) as a pale yellow solid.1H-NMR (CDC13) : 8.32 (2H,m); 7.44 (2H,m); 6.52 ( 1H, q, J=5.8 Hz); 1.94 (3H, d, J=5.5Hz) . |
88% | With pyridine In chloroform at 0 - 20℃; | Step 1: 1-Chloroethylchloroformate (7.8 ml, 72 mmol, 1 eq.) was added to an ice-cold solution of p-nitrophenol (10 g, 72 mmol) in chloroform (100 mL), followed by drop wise addition of pyridine (8.8 ml, 108 mmol, 1.5 eq.) over a period of 20 min. The mixture was stirred in the ice-cold bath for 15 min, and then at room temperature overnight. The reaction mixture was sequentially washed with water, 1 N hydrochloric acid, water, 1 N sodium hydroxide, water, and brine. The organic phase was dried over Na2SO4, and concentrated to give yellow oil which, upon standing, crystallized to afford the corresponding chloroethyl carbonate (15.5 g, 88percent). |
85% | With triethylamine In dichloromethane at 0 - 20℃; | To an ice-cold solution of 4-nitrophenol (2.0 g, 15 mmol) and triethylamine (1.6 g, 16 mmol) in dichloromethane (20 ml) was added a solution of 1-chloroethyl chloroformate (2.1 g, 19 mmol) in dichloromethane, and the mixture was stirred for 15 min at 0 °C and then overnight at room temperature. The mixture was extracted with dichloromethane (50 ml), washed successively with water (50 ml), 0.5 N sodium hydroxide (50 ml), saturated aqueous sodium chloride solution (50 ml), and water (3 x 50 ml), and dried over Na2SO4. The dichloromethane solution was filtered and evaporated under reduced pressure, and the residue was purified by silica gel column chromatography with chloroform (100percent) as eluent to furnish pure 1-chloroethyl 4- nitrophenyl carbonate, as a white solid in 85percent yield. |
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