Structure of 4540-87-8
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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. : | 4540-87-8 |
Formula : | C10H14BNO4 |
M.W : | 223.03 |
SMILES Code : | O=C(NCCB(O)O)OCC1=CC=CC=C1 |
MDL No. : | MFCD11505922 |
InChI Key : | KHMDIKNZIMHPTI-UHFFFAOYSA-N |
Pubchem ID : | 46739751 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.3 |
Num. rotatable bonds | 7 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 3.0 |
Molar Refractivity | 59.44 |
TPSA ? Topological Polar Surface Area: Calculated from |
78.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.73 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.23 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.13 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.04 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.01 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.5 |
Solubility | 7.08 mg/ml ; 0.0318 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.96 |
Solubility | 2.43 mg/ml ; 0.0109 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.25 |
Solubility | 1.25 mg/ml ; 0.00561 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) |
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 |
-7.14 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 |
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 |
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) |
2.18 |
* 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 |
---|---|---|
43.14% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In water; toluene; at 70.0℃; for 16.0h;Inert atmosphere; | In a 500-nil 3-necked round-bottom flask purged and maintained with an inertatmosphere of nitrogen was placed 7-bromoquinolin-4-yl trifluoromethanesulfonate (7.5g, 21.06 mmol, 1 equiv), C52CO3 (20585.8 mg, 63.18 mmol, 3.0 equiv), (2- [[(benzyloxy)carbonyljaminojethyl)boronic acid (9394.4 mg, 42.12 mmol, 2 equiv), and Pd(dppf)C12 (1541.0 mg, 2.11 mmol, 0.1 equiv) in toluene (200 mL) and H20 (50 mL). The resulting solution was stirred for 16 hours at 70 C. The resulting mixture was cooled to room temperature and concentrated. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 3.5 g (43.14%) of benzyl N-[2- (7-bromoquinolin-4-yl)ethyljcarbamate as a white solid. LC-MS: [M+Hj = 385.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.75 g | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; at 100.0℃; for 4.0h;Inert atmosphere; | To 2-((tert-butoxycarbonyl)amino)-2-(4-bromophenyl)acetate 1 g (2.91 mmol) was added <strong>[4540-87-8](2-(((benzyloxy)carbonyl)amino)ethyl)boronic acid</strong> 0.97 g (4.36 mmol, 1.5 eq), cesium carbonate 2.84 g (8.72 mmol, 3 eq), Pd(dppf)Cl . 2dichloromethane 0.24 g (0.29 mmol, 0.1 eq), followed by dioxane (19 mL) and degassed 3X under an atmosphere of argon. The reaction mixture was heated at 100 oC for 4 h, cooled at RT, diluted with dichloromethane, filtered through Celite, washed with water/brine, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel (30% ethyl acetate/hexanes) to afford the title compound, 0.75 g. ESI- MS m/z 443 (M+H)+. |
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