Structure of 51716-63-3
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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. : | 51716-63-3 |
Formula : | C8H10O2 |
M.W : | 138.16 |
SMILES Code : | O=C(C[C@@]1([H])C2)C[C@]1([H])CC2=O |
MDL No. : | MFCD00003771 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.75 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 36.74 |
TPSA ? Topological Polar Surface Area: Calculated from |
34.14 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.17 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.35 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.94 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.65 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.9 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.86 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.48 |
Solubility | 46.2 mg/ml ; 0.334 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.1 |
Solubility | 172.0 mg/ml ; 1.24 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.39 |
Solubility | 5.69 mg/ml ; 0.0412 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) |
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 |
-7.39 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) |
2.3 |
* 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 |
---|---|---|
80% | With hydrogenchloride; acetic acid; In water; for 3.5h;Reflux; Inert atmosphere; | Step 2 (cis)- Bicyclo[3.3.0]octane-3,7-dione; (cis)-Tetramethyl bicyclo[3.3.0]octane-3,7-dioxo-2,4,6,8-tetracarboxylate 14b (6.75 g, 0.02 mol) was dissolved in 3.3 mL of acetic acid followed by the addition of 30 mL of 1 M hydrochloric acid. The reaction solution was heated to reflux for 3.5 hours and then cooled down to room temperature. The reaction solution was extracted with dichloromethane (50 mL×3). The combined orgnic phase was concentrated under reduced pressure, added with 100 mL of dichloromethane, added dropwise with saturated sodium bicarbonate solution to adjust pH to 7 and seperated. The organic phase was dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure to obtain the title compound (cis)-bicyclo[3.3.0]octane -3,7-dione 14c (2 g, yield: 80.0%) as a white solid. |
80% | Step 2 (cis)-Bicyclo[3.3.0]octane-3,7-dione (cis)-Tetramethyl bicyclo[3.3.0]octane-3,7-dioxo-2,4,6,8-tetracarboxylate 14b (6.75 g, 0.02 mol) was dissolved in 3.3 mL of acetic acid followed by the addition of 30 mL of 1 M hydrochloric acid. The reaction solution was heated to reflux for 3.5 hours and then cooled down to room temperature. The reaction solution was extracted with dichloromethane (50 mL*3). The combined organic phase was concentrated under reduced pressure, added with 100 mL of dichloromethane, added dropwise with saturated sodium bicarbonate solution to adjust pH to 7 and separated. The organic phase was dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure to obtain the title compound (cis)-bicyclo[3.3.0]octane-3,7-dione 14c (2g, yield: 80.0%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With toluene-4-sulfonic acid; In benzene;Heating / reflux; | Preparation of 7,7-(ethylidene acetal)bicyclo[3.3.0] octane-3-one 1; bIn a 250 ml round bottom flask equipped with a water segregator, tetrahydro-pentalene-2,5-dione 1a (3 g, 21 mmol) and ethane-1,2-diol (1.03 mL, 18.5 mmol) were dissolved in 150 mL benzene under stirring, then 4-methylbenzenesulfonic acid (50 mg, 0.21 mmol) was added. Upon completion of the addition, the reaction mixture was heated to reflux overnight and then cooled to room temperature. The solvent of benzene was removed under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound 7,7-(ethylidene acetal)bicyclo[3.3.0] octane-3-one 1b (1.8 g, yield 56%) as a colorless oil.MS m/z (ESI): 183.5 [M+1]. |
40% | With toluene-4-sulfonic acid; In toluene; at 100℃; for 10h; | To (3as, 6as) -tetrahydropentadiene-2,5 (1H, 3H) -dione 1a (100 g, 725 mmol), ethylene glycol (40.4 g, 652 mmol), to the mixture with toluene (1.6 L), p-toluenesulfonic acid (12.4 g, 72.4 mmol) was added and the reaction mixture was heated to 100 C and stirred for 10 hours. Cool to room temperature and remove the solvent under reduced pressure. The residue was added with water and extracted with ethyl acetate (500 mL × 3). The combined organic phases were dried over anhydrous sodium sulfate, filtered to remove the drying agent, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3/1) to obtain the target product (3aR,6aS)-tetrahydro-1H-spiro[pentalene-2,2'-[1,3]dioxolane]-5(3H)-one 1b (53 g, yellow oil), yield: 40%. |
With toluene-4-sulfonic acid; In toluene; at 130℃; for 3h; | Step 1 : To a solution of (3as,6as)-tetrahydropentalene-2,5(1 y,3H)-dione (500 mg, 3.62 mmol) in toluene (60 mL) was added ethylene glycol (226 mg, 3.65 mmol) and TsOH (20 mg) and the mixture was stirred at 130C for 3h, diluted with water and extracted with EtOAc. The organic portion was washed with brine, dried over Na2S04, filtered and concentrated to give (3a'R,6a'S)- tetrahydro-1 '/-/-spiro[[1 ,3]dioxolane-2,2'-pentalen]-5'(3'/-/)-one lnt-11a-1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With pyridinium p-toluenesulfonate; In toluene;Dean-Stark; Reflux; Inert atmosphere; | To a solution of <strong>[51716-63-3](3as,6as)-tetrahydropentalene-2,5(1H,3H)-dione</strong> (15 g, 108.57 mmol) in toluene (150 mL) was added 2, 2-dimethylpropane-1,3-diol (11.31 g, 108.57 mmol), followed by the addition of PPTS (250 mg) at rt. The reaction mixture was refluxed overnight with a Dean-Stark trap under N 2 atmosphere. After cooled to rt, the reaction mixture was concentrated under vacuum to remove the volatile. The residue was purified by silica gel flash column chromatography (PE: EtOAc = 20: 1) to give the title compound (16 g, yield: 66%) as a white solid. |
A138352 [74513-16-9]
Tetrahydropentalene-2,5(1H,3H)-dione
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A138352 [74513-16-9]
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