Structure of 6274-50-6
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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. : | 6274-50-6 |
Formula : | C12H16O3 |
M.W : | 208.25 |
SMILES Code : | CC(C)(C1=CC=C(OC)C=C1)C(OC)=O |
MDL No. : | MFCD19441873 |
InChI Key : | VUNAVDASMZBUSC-UHFFFAOYSA-N |
Pubchem ID : | 235766 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.42 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 58.3 |
TPSA ? Topological Polar Surface Area: Calculated from |
35.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.71 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.61 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.15 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.48 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.44 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.81 |
Solubility | 0.324 mg/ml ; 0.00156 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.01 |
Solubility | 0.206 mg/ml ; 0.000987 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.43 |
Solubility | 0.0772 mg/ml ; 0.000371 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) |
Yes |
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 |
-5.72 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 |
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) |
1.56 |
* 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 |
---|---|---|
91% | With potassium <i>tert</i>-butylate In tetrahydrofuran at -78 - 20℃; for 1 h; | To a solution of methyl 2-(4-methoxyphenyl)acetate (10.0 g, 55.49 mmol) in THF (100 mL) at -78 °C was added methyl iodide (23.64 g, 166.5 mmol) very slowly. KO?-Bu (18.68 g, 166.5 mmol) was then added portionwise over 30 min and the reaction mixture was stirred at -78 °C for 1 h followed by rt for another 1 h. The reaction was quenched by the addition of water (25 mL) and extracted with EtOAc (2 x 250 mL). The organic layer was dried over Na2S04 and concentrated to obtain the title compound (10.46 g, 91percent). |
75.59% | at -60℃; for 0.5 h; | To a solution of methyl 2-(4-methoxyphenyl)acetate (4.0 g, 22.22 mmol) in THF (25 mL), was added iodomethane (9.45 g, 66.66 mmol) and the reaction mixture was cooled to -60 °C, followed by addition of potassium tert-butoxide (7.48 g, 66.66 mmol) portion wise. The reaction mixture was stirred for 30 minutes at the same temperature. After completion of the reaction, water (30 mL) was added into the reaction mixture at -60 °C and extracted with ethyl acetate (2 x 250 mL). The combined organic layers were dried over NaiSC and concentrated to obtain a crude product which was purified by silica gel column chromatography using 2.5percent EtOAc/hexanes to provide the title compound (3,52 g, 75,59percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: With 2,2,6,6-tetramethylpiperidinyl-lithium In toluene at 20℃; for 0.25 h; Glovebox Stage #2: With palladium(l) tri-tert-butylphosphine iodide dimer In toluene at 20℃; Glovebox |
General procedure: Inside the glovebox, lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 70.7 mg, 0.48 mmol, 1.2 eq.) was dissolved in toluene (1.5 mL) and carbonyl compound (3, 0.48 mmol, 1.2 eq.) was added. After 15 min of stirring at ambient temperature a solution of Pd(I) iodo dimer (2, 3.5 mg, 0.004 mmol, 1 molpercent for aryl iodides; 17.4 mg, 0.02 mmol, 5 molpercent for aryl bromides) and aryl halide (4, X = I or Br, 0.4 mmol, 1.0 eq.) in toluene (0.5 mL) was added. After 4-18 h of further stirring at ambient temperature (reaction progress was monitored by GCMS), the crude was directly adsorbed onto silica (washing with diethyl ether) and purified by flash column chromatography. |
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