Structure of 461432-23-5
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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. : | 461432-23-5 |
Formula : | C15H14BrClO |
M.W : | 325.62 |
SMILES Code : | CCOC1=CC=C(CC2=C(Cl)C=CC(Br)=C2)C=C1 |
MDL No. : | MFCD11042292 |
InChI Key : | ZUNCHZBITMUSRD-UHFFFAOYSA-N |
Pubchem ID : | 9996449 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 79.9 |
TPSA ? Topological Polar Surface Area: Calculated from |
9.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.56 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.5 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.09 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.01 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.54 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.94 |
Log S (ESOL):? ESOL: Topological method implemented from |
-5.55 |
Solubility | 0.000911 mg/ml ; 0.0000028 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.45 |
Solubility | 0.00115 mg/ml ; 0.00000353 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-7.29 |
Solubility | 0.0000165 mg/ml ; 0.0000000507 mol/l |
Class? Solubility class: Log S scale |
Poorly 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) |
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) |
Yes |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
Yes |
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 |
-4.38 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
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 |
2.0 |
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) |
2.11 |
* 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 |
---|---|---|
100% | Take 112g of compound N-9 (0.347mol, 1.25eq) and 720ml of anhydrous tetrahydrofuran and stir, replace with nitrogen three times, cool down and control the temperature -80-75, and add 240ml 1.6M n-butyllithium n-hexane solution ( 0.347mol, 1.25eq), the dripping time is 2h, after dripping, keep stirring for 1h; continue to control the temperature -80-75, add dropwise the tetrahydrofuran solution of compound N-8 (120g compound N-8 (0.277mol, 1.0eq) dissolved in 240ml tetrahydrofuran), the dripping time is 2h, after dripping, keep stirring for 2h until TLC monitors that the reaction is complete (petroleum ether: ethyl acetate=6:1 as the developing solvent, and no compound N-8. Complete); Control the temperature to below -20C, add dropwise 600ml, 10wt% ammonium chloride aqueous solution, then return to 10C, extract with 1600ml dichloromethane, take the organic phase, wash with 1500ml saturated brine, and dry with anhydrous sodium sulfate , Concentrate under reduced pressure to no cuts to obtain 250 g of compound N-10-a, which is continuously cast in step S2 at a yield of 100%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a 250 mL of dry round-bottom flask, 6.51 g (20 mmol) of (2-chloro-5-bromophenyl) (4-ethoxyphenyl) methane and 60 mL of dry THF are added, and the magneton is added. After purging with nitrogen gas, the mouth of the round-bottom flask is sealed with a soft rubber plug. The flask is placed in a liquid nitrogen-ethanol system to cool to -78C, and stirred. 12.5 mL of n-butyl lithium solution with a concentration of 1.6 M (20 mmol n-butyl lithium) is added slowly with a injector, , and stirred for another half an hour at this temperature after the addition, and then the solution prepared by dissolving 8.65 g (20 mmol) of M-4 in 40 mL of dry THF is added slowly with a injector. After the addition, the reaction mixture is stirred for another 1 hour at this temperature. After which, at this temperature, the solution prepared by dissolving 4.81 g (50 mmol) of methanesulfonic acid in 20 mL of methanol is added slowly with a injector, , and stirred at room temperature for 12 hours after the addition. (0266) The reaction mixture is dumped into 400 mL of ice water, stirred, the pH value is adjusted to pH = 4-6 with saturated NaHCO3 solution, and extracted with 100 mL x 3 of dichloromethane. The organic phases are combined, washed with 0.1 mol/l aqueous NaCl solution, and dried with anhydrous sodium sulfate, evaporated to dryness on the rotary evaporator, and the resulting residue is the crude product of M-5. The crude product of M-5 is analyzed using electrospray ionization-mass spectrometry (ESI-MS), the mass-charge ratio of which is m/z = 693 ([M+H]+). Wherein, the crude product can be used for the next step of reaction without purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | To a cold solution (-78?°C) of compound 15 (470?mg, 1.45?mmol) in dry THF (3?mL) 1.6?N solution of n-BuLi in hexanes (0.13?mL) was added dropwise. The mixture was stirred at this temperature for 45?min and to this mixture a solution of <strong>[67442-07-3]2-chloro-N-methoxy-N-methylacetamide</strong> (200?mg, 1.45?mmol) in dry THF (2?mL) was added dropwise at -78?°C. Stirring was continued for 3?h?at this temperature where the consumption of the starting material was checked by TLC. Saturated aqueous solution of NH4Cl (5?mL) was then added, followed by extraction with of DCM (3?*?8 mL). The combined organic layers ware dried over Na2SO4, the solvent was removed under reduced pressure and the residue was chromatographed on a silica gel column (hexane/ethyl acetate 12:1) to give product 16 (455?mg, 98percent) as a colorless oil. FTIR (neat film) 3033, 1702, 1629?cm-1. 1H NMR (500?MHz, CDCl3) delta 7.74 (d, J?=?2.0?Hz, 1H), 7.72 (dd, J?=?8.3, 2.0?Hz, 1H), 7.47 (d, J?=?8.3?Hz, 1H), 7.09 (d, J?=?8.6?Hz, 2H), 6.83 (d, J?=?8.6?Hz, 2H), 4.58 (s, 2H), 4.07 (s, 2H), 4.00 (q, J?=?7.0?Hz, 2H), 1.40 (t, J?=?7.0?Hz, 3H). 13C NMR (126 MHz, CDCl3) delta 190.2, 157.7, 140.4, 140.2, 132.8, 130.8, 130.2, 130.1, 129.9, 127.5, 114.7, 63.4, 45.8, 38.3, 14.7. LC-MS (ESI positive) m/z: 361 [M+K]+ HRMS m/e: C17H16KO2 [(M+K)+] calcd: 361.0159, found: 361.0156. |
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