Structure of 14180-51-9
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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. : | 14180-51-9 |
Formula : | C20H19O2P |
M.W : | 322.34 |
SMILES Code : | COC1=CC=C(P(C2=CC=C(OC)C=C2)C3=CC=CC=C3)C=C1 |
MDL No. : | MFCD00048993 |
InChI Key : | BJPHLVZNHDIUNY-UHFFFAOYSA-N |
Pubchem ID : | 518897 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 23 |
Num. arom. heavy atoms | 18 |
Fraction Csp3 | 0.1 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 98.13 |
TPSA ? Topological Polar Surface Area: Calculated from |
32.05 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.87 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.55 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.46 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.16 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.52 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.31 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.95 |
Solubility | 0.00358 mg/ml ; 0.0000111 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.95 |
Solubility | 0.00365 mg/ml ; 0.0000113 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-7.77 |
Solubility | 0.00000542 mg/ml ; 0.0000000168 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) |
No |
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 |
-5.04 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 |
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) |
3.79 |
* 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 |
---|---|---|
96% | With dihydrogen peroxide; In acetone; at 20℃; for 1h; | 5 g of compound 2a was transferred to a round bottom flask, 50 ml of acetone was added, and H2O2 (1.1 eq) was slowly added dropwise. Stir at room temperature Mix for 1 h, vacuum distillation of acetone. The crude product was dissolved in dichloromethane and saturated brine was washed until the KI test paper was kept blue. The methylene chloride was distilled off to give the product as an oil. After standing overnight, the oily substance was crystallized and recrystallized from cyclohexane as a solvent to give a white solid in 96% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | The magnesium powder was washed with hydrochloric acid and acetone separately, and dried. THF was refluxed with metal Na to benzophenone to become dark purple. The new Mg powder was added to the reaction apparatus, N2 was replaced three times, and I2 granules and purified THF were successively added. N2, the dried compound 1a (4-bromoanisole) was transferred to a dropping funnel. The reaction was initiated by heating, and the THF solution of 4-bromoanisole was slowly added dropwise.After completion of the dropwise addition, the mixture was stirred at room temperature for 1 h to give a dark black mixture. Benzyl phosphorus dichloride slowly added to the Grignard reagent, dropping finished, stirring 2h. The reaction mixture was slowly added to a 10% aqueous solution of ice water and extracted with ether. The solvent was evaporated under reduced pressure to give a crude product as a yellow solid. The crude product was recrystallized from ethanol to give a white solid. Yield: 78%. | |
175.3 g | Grignard reagent was prepared using 4-bromoanisole (TokyoChemical Industry Co., Ltd., trade CD: B0547) 374.6g, magnesium (Sigma-AldrichJapan joint company, trade CD: 219-0040-5) 65.4g and dehydrated THF (Kanto ChemicalCo., Inc. Ltd., product CD: 41001-75) 3L. Then, a solution of dichlorophenylphosphine (Tokyo Chemical Industry Co.,Ltd., trade CD: P0207) 179g dissolved in dehydrated THF500mL was slowly added.The reaction solution was filtered, concentrated, and dissolved by adding chloroform(Sigma-Aldrich Japan joint company made: Product CD: 205-3410-8) 2L. Thechloroform solution was extracted 4 times with purified water 500 mL. Theresulting chloroform layer was dried over magnesium sulfate (Sigma-Aldrich JapanLLC, trade CD: 219-0510-5), and the precipitate was filtered, and the filtratewas concentrated. The resulting concentrate was recrystallized with ethanol(Sigma-Aldrich Japan joint company, trade CD: 209-0780-3) 350mL, then driedunder reduced pressure to obtain 175.3g of bis(4-methoxy-phenyl) phenyl phosphine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.95% | General procedure: A mixture of Ru3(CO)10(arphos) (52.3mg, 0.051mmol) and PCy3 (14.0mg, 0.051mmol) was heated in refluxing hexane (25ml) for 1h. Completion of the reaction was monitored by TLC. The solvent was removed under reduced pressure. The reaction mixture was separated by preparative TLC (2:3 dichloromethane:hexane), affording three bands. The first band (Rf=0.76) gave the starting material Ru3(CO)10(arphos), the second band (Rf=0.57) gave the major product, characterised as Ru3(CO)9(arphos)PCy3, and the third band was only obtained in trace amounts and was not characterised. The results are as follows. Yield: 21.7mg (33.28%), |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
All manipulations were performed under a dry oxygen-free dinitrogen atmosphere using standard Schlenk techniques, under nitrogen atmosphere. Tris (4-methylphenyl) phosphine was used as ligand, and μ-bis (diphenylarsino) methane decacarbonyltriruthenium(0) was prepared by two step route.[25] The title compound was obtained by refluxing equimolar quantities of Ru3(CO)10(μ-Ph2AsCH2AsPh2) (105.5 mg, 0.1 mmol) and tris (4-methoxyphenyl) phosphine (32.23 mg, 0.1 mmol) in hexane under a nitrogen atmosphere. Crystals suitable for Xray diffraction were grown by slow solvent/solvent diffusion of CH3OH into CH2Cl2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | at 120℃; for 6h;Inert atmosphere; Schlenk technique; | General procedure: A. TfOCH2CF2H(0.514 g, 2.4 mmol) and triphenylphosphine (0.525 g, 2 mmol) were placed in aclosed Schlenk flask under a N2 atmosphere. The mixture was stirredat 120 oC for 24 h and cooled to room temperature. The resultingsolid was washed by diethyl ether, recrystallized from CH2Cl2/hexane,and dried in vacuum to give 0.66 g of (E)-ethene-1,2-diylbis(triphenylphosphonium)ditriflate (3a) as a white solid (0.78 mmol, 78%).2 |