Structure of 156185-63-6
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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. : | 156185-63-6 |
Formula : | C13H25NO3 |
M.W : | 243.34 |
SMILES Code : | O=C(N1CCC(CCCO)CC1)OC(C)(C)C |
MDL No. : | MFCD02677712 |
InChI Key : | OXPWHPCCUXESFQ-UHFFFAOYSA-N |
Pubchem ID : | 2800739 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.92 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 72.18 |
TPSA ? Topological Polar Surface Area: Calculated from |
49.77 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.11 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.89 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.03 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.71 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.71 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.09 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.14 |
Solubility | 1.75 mg/ml ; 0.00719 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.56 |
Solubility | 0.674 mg/ml ; 0.00277 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.92 |
Solubility | 2.93 mg/ml ; 0.0121 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 |
-6.44 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) |
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 |
---|---|---|
With sodium hydroxide; potassium hydrogensulfate; In 1,4-dioxane; | b 3-[N-(tert-butoxycarbonyl)piperidin-4-yl]propanol A solution of 6 g of di(tert-butyl)carbonate in 20 ml of dioxan was introduced into a solution of 3.2 g of 3-(4-piperidinyl)propanol in 50 ml of dioxan containing 25 ml of a 2N aqueous solution of sodium hydroxide, cooled at 0° C. The mixture was allowed to react for 16 hours at room temperature. The solution was then evaporated and the residue was extracted with ethylether. The organic layer was washed with a 10percent solution of KHSO4 and then dried over MgSO4. The solvent was evaporated and the residue was chromatographied on silica gel (eluent: CH3 COOEt/cyclohexane:2/8-1/1:v:v). 3 g of the desired compound in the form of an oil were obtained. RMN (CDCl3, 200 MHz) 4.05 ppm (m, 2H); 3.6 (t, 2H); 2.64 (m,2H); 1.7 a 1.1 (m, 18H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | In dichloromethane; at 20℃; for 2h; | Preparation 144-(3-Aminopropyl)-piperidine-1-carboxylic acid tert-butyl ester(A). Preparation of 4-(3-hydroxypropyl)-piperidine-1-carboxylic acid tert-butyl ester; Di-tert-butyl dicarbonate (3.66 g, 16.8 mmol) is added to a stirred solution of 3-piperidin-4-yl-propan-1-ol (1.60 g, 11.2 mmol) in anhydrous dichloromethane (20 mL) at ambient temperature under nitrogen. The resultant mixture is allowed to stir for 2 hours. The mixture is directly subjected to chromatography purification on silica gel and eluted with MeOH in dichloromethane 0-3percent to give the title compound as a clear oil (2.40 g, 88percent yield). |
82% | In ethanol; | 1) Synthesis of 3-(1-tert-butoxycarbonyl-4-piperidyl)-1-propanol To a solution of 35.8 g (250 mM) of <strong>[7037-49-2]3-(4-piperidyl)-1-propanol</strong> in 500 ml of ethanol was added 54.6 g (250 mM) of di-tert-butyl dicarbonate dropwise and the mixture was stirred at room temperature for one hour. The solvent was then distilled off under reduced pressure and the residue was purified by column chromatography (ethyl acetate-hexane=1/1 ethyl acetate) to provide the title compound as light-yellow oil (50.2 g, 82percent). 1H-NMR (200 MHz, CDCl3) delta: 0.96-1.41 (m, 5H), 1.45 (s, 9H), 1.49-1.78 (m, 4H), 2.61-2.74 (m, 2H), 3.62 (t, J=6.4 Hz, 2H), 4.04-4.10 (m, 2H). |
With sodium hydroxide; In 1,4-dioxane; at 0 - 20℃; for 12h; | To a solution of 3- (piperidin-4-yl) propan-1-ol (8.1 g, 56.7 mmol) and 3M NaOH (100 mL) in dioxane (300 mL) was added a solution of Boc2O (15.0 g, 68.0 mmol) in dioxane (30 mL) dropwise at 0. After stirring at rt for 12 h, the solvent was removed under reduced pressure and the residue was dissolved in EtOAc (600 mL) . The organic phase was washed with sat. NH4Cl (30 mL) , NaHCO3 (30 mL) and brine (30 mL) , dried over anhydrous Na2SO4, filtered and concentrated to afford tert-butyl 4- (3-hydroxypropyl) piperidine-1-carboxylateas which was used in next step without purification. LRMS m/z (M-55) 188.1 found, 188.2 required. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In 1,4-dioxane; at 20℃; for 2h; | The solution of tert-butyl 4- (3-hydroxypropyl) piperidine-1-carboxylate (5 g, 20.6 mmol) in 2M HCl/1, 4-dioxane (20 mL) was stirred for 2 h at rt. Then the mixture was concentrated in vacuo to give crude 3- (piperidin-4-yl) propan-1-ol. LRMS m/z (M+H) 144.0 found, 144.1 required |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.5 g | With diisobutylaluminium hydride; In dichloromethane; at -78 - 0℃; for 2h;Inert atmosphere; | In a 500-ml flask swept with nitrogen, 5 g (17.53 mmol) of <strong>[162504-75-8]tert-butyl 4-(3-methoxy-3-oxopropyl)piperidine-1-carboxylate</strong> (prepared according to the method reported in J. Med. Chem. 1995, 38, p 3332-3341 by taking commercial tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate as the starting product) in 100 ml of dichloromethane. The medium is cooled to -78 C. and 52.6 ml (52.6 mmol) of a 1 M solution of DIBAL-H in dichloromethane are added dropwise. It is stirred for 2 h at 0 C. It is cooled to -78 C. and a saturated solution of potassium sodium tartrate is added. After return to room temperature, it is extracted and then the organic phase is dried on Na2SO4, filtered and evaporated, and 4.5 g of the crude oil are obtained, used as is in the next step. |
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