Structure of 828-52-4
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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. : | 828-52-4 |
Formula : | C10H16O3 |
M.W : | 184.23 |
SMILES Code : | OCC12CCC(CC1)(CC2)C(O)=O |
MDL No. : | MFCD09835291 |
InChI Key : | CPVMAYNPSFMOGK-UHFFFAOYSA-N |
Pubchem ID : | 301131 |
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 | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 48.37 |
TPSA ? Topological Polar Surface Area: Calculated from |
57.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.53 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.7 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.4 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.31 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.66 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.32 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.29 |
Solubility | 9.42 mg/ml ; 0.0511 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.49 |
Solubility | 6.02 mg/ml ; 0.0327 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.28 |
Solubility | 9.69 mg/ml ; 0.0526 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 |
-6.93 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 |
0.56 |
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) |
3.09 |
* 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 |
---|---|---|
With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 80℃; for 16.0h; | Example 93 <strong>[828-52-4]4-Hydroxymethylbicyclo[2.2.2]octane-1-carboxylic acid</strong> benzyl ester (XVIII, Step O) <strong>[828-52-4]4-Hydroxymethylbicyclo[2.2.2]octane-1-carboxylic acid</strong> (XVII, Example 14, 24.8 g 135 mmol) is dissolved in DMF (950 ml). Anhydrous potassium carbonate (25 g, 181 mmol) is added to the solution slowly. Benzyl bromide (22 g, 12.94 mmol) is then added. The reaction mixture is heated at 80 for 16 hr. To the reaction mixture is added water (150 ml) and concentrated to give an oil, which was dissolved in ethyl acetate/hexane (5/1, 500 ml). The mixture is washed with saline (2*200 ml), dried over anhydrous sodium sulfate and concentrated to give the title compound, NMR (400 MHz, CDCl3) delta 7.39, 5.11, 3.28, 1.84 and 1.41. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 92 4-Hydroxymethylbicyclo[2.2.2]octane-1-carboxylic acid (XVII, Step N) Lithium hydroxide (2 N, 250 ml) is added to a mixture of 4-hydroxymethyl-bicyclo[2.2.2]octane-1-carboxylic acid methyl ester (XVI, Example 91) in a mixture of THF (50 ml) and methanol (75 ml). The resulting reaction mixture is stirred at 20-25 for 16 hr, and then concentrated. The residue is diluted with water (30 ml) and washed with methylene chloride (100 ml) and ethyl acetate (100 ml). The aqueous layer is acidified with concentrated hydrochloric acid pH about 0 and extracted with ethyl acetate (3*250 ml). The ethyl acetate layers are combined and washed with saline (3*50 ml), dried over anhydrous sodium sulfate and concentrated to give the title compound, NMR (400 MHz, CDCl3) delta 3.09, 1.72 and 1.29. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium tetrahydroborate; In water; at 20℃; | Sodium borohydride (5.8 g, 0.15 mol) was added portionwise to an aqueous solution (120 mL) of 4-(methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid (6.5 g, 0.03 mol).The reaction mixture was stirred at room temperature overnight.Ice water bath cooling,Dilute aqueous hydrochloric acid (1.0M) to adjust the pH to 2-3,Solid filter,The cake was washed with cold water (20 mL) and dried under reduced pressure to give compound 9.1(5.66 g, yield: 100%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7% | With ammonium persulfate; silver nitrate; In sulfuric acid; water; acetonitrile; at 80℃; for 1.0h; | Aqueous ammonium persulfate solution (4.56 g, 0.02 mol, 10 mL) was added dropwise to compound 9.1 (3.68 g, 0.02 mol),2-methylpyridine (1.86 g, 0.02 mol)And silver nitrate (340 mg, 2.0 mmol) in 10% aqueous sulfuric acid (30 mL)And acetonitrile (40 mL).The reaction mixture is heated to 80 C,Stir for 1 hour,Then cool to ambient temperature,Use concentrated ammonia to adjust the pH to 8-9.Ethyl acetate (100 mL×2) was extracted and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure.The residue was purified by flash chromatography (petroleum ether/ethyl acetate = 1/1) to give compound 9.2 (200 mg, yield: 7%) as a pale yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 0 - 100℃; for 6.0h; | To a 25 mL pear shaped flask were added <strong>[828-52-4]4-(hydroxymethyl)bicyclo[2.2.2]octane-1-carboxylic acid</strong> (160 mg, 0.85 mmol) (Kiesman W. F. et. al. WO 2001/034610) and BOP (38 mg, 0.85 mmol) in DMF (1 mL) followed by methyl (Z)-3-(N'-hydroxycarbamimidoyl)benzoate (Tung, R. D. WO 2016/073545) (150 mg, 0.77 mmol). To this mixture was added Et3N (0.32 mL, 2.3 mmol) at 0 C. The reaction mixture was stirred for 2 h at rt, and 4 h at 100 C. The reaction was cooled, the solvent was concentrated and the residue was dissolved in EtOAc (50 mL). The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash column chromatography (24 g silica gel column; A=Hex, B=EtOAc; 15 min grad.; 0-30% B; flow rate=24 mL/min). The pure fractions were combined, concentrated and dried in vacuo to afford the title compound (120 mg, 45% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) delta=8.54 (t, J=1.5 Hz, 1H), 8.26 (dt, J=7.8, 1.5 Hz, 1H), 8.16 (dt, J=7.9, 1.6 Hz, 1H), 7.74 (t, J=7.7 Hz, 1H), 5.76 (s, 1H), 4.46 (t, J=5.5 Hz, 1H), 3.99-3.85 (m, 3H), 3.11 (d, J=5.4 Hz, 2H), 1.99 (d, J=7.8 Hz, 6H), 1.55-1.39 (m, 6H). MS (ESI) 343 (M+H). |
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