Structure of 63930-59-6
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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. : | 63930-59-6 |
Formula : | C6H8O3 |
M.W : | 128.13 |
SMILES Code : | CC(OC1CC(C1)=O)=O |
MDL No. : | MFCD11976057 |
InChI Key : | FWHLIVHQAGFBOA-UHFFFAOYSA-N |
Pubchem ID : | 11788311 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.67 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 30.33 |
TPSA ? Topological Polar Surface Area: Calculated from |
43.37 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.97 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.36 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.28 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.11 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.92 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.34 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.28 |
Solubility | 67.9 mg/ml ; 0.53 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.09 |
Solubility | 105.0 mg/ml ; 0.816 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.68 |
Solubility | 26.5 mg/ml ; 0.207 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 |
-7.34 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 |
1.0 |
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) |
1.6 |
* 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 |
---|---|---|
54% | In dichloromethane; at 20℃; for 18.0h;Cooling with ice; | (A) To an ice-cold solution of <strong>[63930-59-6]3-acetoxycyclobutanone</strong> (2.563g, 20 mmol) in anhydrous DCM (100 mL) was added ethyl triphenylphosphoranylidene acetate (9.06 g, 26 mmol) and the resulting mixture was stirred at rt for 18 h. The reaction was then concentrated under reduced and the resultant residue was purified by silica gel chromatography (0-20% EtOAc/heptanes) to provide ethyl 2-(3-acetoxycyclobutylidene)acetate (2.15 g, 54%) as a slightly yellowish oil. LC/MS: Calcd. for C10H14O4: 198.22, found: 199.1 [M+H]+. |
54% | In dichloromethane; at 20℃; for 18.0h;Cooling with ice; | (A) To an ice-cold solution of <strong>[63930-59-6]3-acetoxycyclobutanone</strong> (2.563 g, 20 mmol) in anhydrous DCM (100 mL) was added ethyl triphenylphosphoranylidene acetate (9.06 g, 26 mmol) and the resulting mixture was stirred at rt for 18 h. The reaction was then concentrated under reduced and the resultant residue was purified by silica gel chromatography (0-20% EtOAc/heptanes) to provide ethyl 2-(3-acetoxycyclobutylidene)acetate (2.15 g, 54%) as a slightly yellowish oil. LC/MS: Calcd. for C10H14O4: 198.22, found: 199.1 [M+-H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31%; 30% | With sodium tris(acetoxy)borohydride; In dichloromethane; for 3.0h; | To a solution of the compound of Preparation P (1.5 g; 7.63 mmol) in DCM (76 mL) were added (tert-butyldimethylsilyloxy)acetaldehyde (4.44 mL; 21 mmol) and NaBH(OAc)3(9.5 g; 45 mmol). The reaction mixture was stirred for 3 h. Sat. aq. NaHCO3 (80 mL) and DCM (10 mL) were added. The aq. layer was extracted with DCM (2 x 70 mL). The evaporation residue was purified by CC (Hept-EA) to afford the title compound as a yellow oil (2.29 g; 94% yield).?Starting from the compound of Preparation P (0.5 g; 2.56 mmol) and <strong>[63930-59-6]3-oxocyclobutyl acetate</strong> (0.366 g, 2.85 mmol) and proceeding in analogy to Preparation U, the title compounds were obtained respectively after CC (Hept-EA). The first eluting isomer, the (ir,3r)-isomer (trans) was obtained as a yellowish oil (0.2 17 g; 31% yield). The secondeluting isomer, the (ls,3s)-isomer (cis) was obtained as a yellowish oil that cristallized on standing (0.21 g; 30% yield).?H NMR (CDC13) oe: 5.09 (m, 1H); 3.66-3.57 (m, 2H); 3.24 (m, 1H); 3.19 (m, 1H); 3.09-3.01 (m, 2H); 2.29-2.22 (m, 2H); 2. 14-2.06 (m, 2H); 2.02 (s, 3H).MS (ESI, mlz): 271.9 [M+H] for C,,H,4NO2Br; tR = 0.45 mm.?H NMR (CDC13) oe: 5.09 (m, 1H); 4.71 (m, 1H); 3.62-3.54 (m, 2H); 3.27 (m, 1H); 3.19-3.13 (m, 2H); 2.88 (m, 1H); 2.53-2.48 (m, 2H); 2.02 (s, 3H); 1.99-1.93 (m, 2H). MS (ESI, mlz): 271.9 [M+Hj for C,,H,4NO2Br; tR = 0.44 mm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | In tetrahydrofuran; at -78℃; for 2.0h;Inert atmosphere; | Bromo-(4-chlorophenyl)magnesium (1M in 2-Me-THF) (13.7 mL, 13.4 mmol) was added dropwise to a solution of (3-oxocyclobutyl) acetate (1.72 g, 13.4 mmol) in THF (17 mL) at -78C under N2. The reaction was stirred at -78C for 2h. The reaction was quenched with saturated NH4C1, partitioned in water/iPrOAc and extracted with iPrOAc (3x). The combined organic extracts were washed with water and brine and they were dried over MgS04, filtered and concentrated. The crude mixture was adsorbed on silica and purified by silica gel column with 0-50% iPrO Ac/heptane to afford the title compound (1.19 g, 37% Yield) as a clear oil. |
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