Structure of 23062-51-3
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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. : | 23062-51-3 |
Formula : | C10H15BrO2 |
M.W : | 247.13 |
SMILES Code : | O=C(C1(CC2)CCC2(Br)CC1)OC |
MDL No. : | MFCD22577785 |
InChI Key : | QPKJFWIGJBWLTB-UHFFFAOYSA-N |
Pubchem ID : | 57467434 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.9 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 54.89 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.58 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.24 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.65 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.62 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.97 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.61 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.65 |
Solubility | 0.551 mg/ml ; 0.00223 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.43 |
Solubility | 0.923 mg/ml ; 0.00373 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.01 |
Solubility | 0.242 mg/ml ; 0.000977 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 |
-6.22 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 |
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) |
4.04 |
* 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 |
---|---|---|
94.8% | at 80℃; for 3.66667 h; | To a stirred mixture of XVIII-1 (10 g, 47.2 mmol) in CH2Br2 (100 mL) was added HgO (17.5 g, 80.3 mmol) at rt. The mixture was heated to 80° C. and Br2 (3.6 mL, 47.2 mmol) was added dropwise during 40 min. After addition, the mixture was stirred at 80° C. for 3 h. Then the mixture was cooled to rt, and filtered. The filtrate was treated with MgSO4, filtered and concentrated in vacuo. The residue XVIII-2 (11 g, yield 94.8percent) was used in next step directly. |
71.2% | With bromine In dichloromethane for 3.5 h; Reflux | To a refluxing suspension of 4-(methoxycarbonyl)bicycle [2.2.2] octane- 1- carboxylic acid (3.5 g, 16.49 mmol) compound and mercuric oxide, red (6.07 g, 28.0 mmol) in DCM (60 mL) was added drop wise solution of bromine (1.274 mL, 24.74 mmol) in DCM (25 mL) and refluxing was continued for another 3.5 h. The reaction mixture was filtered through celite and the filtrate was washed with water (2 x 100 mL). The organic layer was dried over Na2S04and concentrated under reduced pressure. The crude was purified by Combiflash Isco (Redisep, 40 g Silica, 6 percent EtOAc in petroleum ether) to yield methyl 4-bromobicyclo [2.2.2] octane-1- carboxylate (2.9 g, 11.73 mmol, 71.2 percent yield) as off white solid.XH NMR (DMSO- d6, δ = 2.50 ppm, 400 MHz): δ 3.56 (s, 3 H), 2.24 - 2.16 (m, 6 H), 1.92 - 1.85 (m, 6 H). |
70% | Stage #1: With sodium hydroxide; phenolphthalein; silver nitrate In water; acetone Stage #2: With bromine In hexane at 20 - 80℃; for 1 h; |
To a suspension of the title compound from the Preparative Example 39, Step C (1.0 g) in acetone (7.5 mL) was added phenolphthaleine (1 crystal). To this mixture was added IM aqueous NaOH until the color of the solution changed to red (pH ~ 8.5). Then a solution Of AgNO3 (850 mg) in H2O (1.25 mL) was added. The formed precipitate (Ag-salt) was collected by filtration, washed with H2O, acetone and Et2O and dried in vacuo at room temperature for 6 h and at 100°C for 18 h. The obtained solid (1.28 g) was suspended in hexane (15 mL), bromine (643 mg) was added dropwise and the mixture was stirred at room temperature for 30 min. Then the mixture was placed in a preheated oil bath (80°C) and stirred at the temperature for another 30 min. The mixture was filtered and the filter cake was washed with Et2O (2 x 30 mL). The combined filtrates were washed with saturated aqueous NaHCO3 (2 x 25 mL), dried (MgSO4), filtered and concentrated to afford the title compound (817 mg, 70percent). [MH]+ = 247/249. |
68.7% | With bromine; mercury(II) oxide In dichloromethane for 1.5 h; Reflux | Intermediate A51D: Methyl 4-bromobicyclo[2.2.2]octane-1-carboxylate To a solution of Intermediate A51A (1.5 g, 7.07 mmol) in CH2Cl2 was added mercury(II) oxide (2.60 g, 12.01 mmol). The suspension was heated at reflux condition. To the reaction mixture was added a solution of bromine (0.473 ml, 9.19 mmol) in CH2Cl2 (5 mL) dropwise under refluxing. The reaction mixture was heated at reflux for 1.5 h and cooled to RT. It was passed through a pad of CELITE®, washed with EtOAc. The filtrate was concentrated. The residue was purified by silica gel chromatography (40 g REDISEP® column, eluting with 0-30percent EtOAc in hexane. Fractions containing the product were combined and evaporated to afford Intermediate A51D (1.2 g, 68.7percent). 1H NMR (400 MHz, chloroform-d) δ ppm 3.65 (s, 3H), 2.35-2.19 (m, 6H), 2.04-1.90 (m, 6H). |
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