Structure of 393781-71-0
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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. : | 393781-71-0 |
Formula : | C11H22N2O2 |
M.W : | 214.31 |
SMILES Code : | C(=O)(OC(C)(C)C)N1CCNCC1CC |
MDL No. : | MFCD03265490 |
InChI Key : | CTCGRXDGXGUOTE-UHFFFAOYSA-N |
Pubchem ID : | 18004789 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.91 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 68.12 |
TPSA ? Topological Polar Surface Area: Calculated from |
41.57 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.82 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.42 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.84 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.15 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.97 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.44 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.8 |
Solubility | 3.4 mg/ml ; 0.0159 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.9 |
Solubility | 2.71 mg/ml ; 0.0127 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.84 |
Solubility | 3.06 mg/ml ; 0.0143 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 |
-6.6 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) |
2.75 |
* 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 N-ethyl-N,N-diisopropylamine; In dichloromethane; | To a solution of 1 ,1-dimethylethyl 2-ethyl-1-piperazinecarboxylate (100mg, 0.467 mmol) in DCM (5ml_) was added di-isopropylethylamine (0.253mL, 1.447 mmol), followed by gradual addition of 4-cyanobenzenesulfonyl chloride (103mg, 0.513 mmol). The reaction mixture was allowed to stir for 1 hour. The reaction mixture was diluted with DCM (1 OmL) and the solution was washed with saturated aqueous sodium bicarbonate solution (1OmL, twice), then with distilled water (1OmL). The organic layer was dried (MgSO4), filtered and reduced in vacuo to yield 1 ,1-dimethylethyl 4-[(4-cyanophenyl)sulfonyl]-2-ethyl-1-piperazinecarboxylate as a crude transparent oil (173mg), MS ES+ve m/z 280 (M+H-100). To 1 ,1-dimethylethyl 4-[(4-cyanophenyl)sulfonyl]-2-ethyl-1-piperazinecarboxylate (173mg, 0.456 mmol) was added hydrogen chloride 1 M solution in 1 ,4 dioxane (1OmL) solution, followed by the addition of 3 drops of water. The reaction mixture was allowed to stir for 14hours. After this time, 5M aqueous HCI (1 ml) was added and the mixture was stirred for 12hours. The reaction mixture was concentrated in vacuo to yield colourless oil. The colourless oil was dissolved in methanol (1 OmL) and passed down a SCX-2 column washing with two column volumes of methanol and eluting the product with 2N ammonia solution in methanol (three column volumes). The fraction containing eluted product was reduced in vacuo to yield 4-[(3-ethyl-1- piperazinyl)sulfonyl]benzonitrile (99mg) as a transparent oil, MS ES+ve m/z 280 (M+H).To a solution of 4-[(3-ethyl-1-piperazinyl)sulfonyl]benzonitrile (99mg, 0.354mol) in tetrahydrofuran (1OmL) was added triethylamine (0.074mL, 0.532mmol) followed by drop wise addition of benzoyl chloride (0.045mL, 0.390mmol). The reaction mixture was allowed to stir for 30minut.es. The reaction mixture was diluted with DCM (1 OmL) and the solution was washed with saturated aqueous sodium bicarbonate solution (1OmL, twice), then 0.1 M hydrochloric acid (1OmL). The organic layer was dried with (MgSO4), filtered and concentrated in vacuo to yield 144mg colourless oil. The oil was dissolved in minimum volume of hot ethyl acetate (~2ml), hot iso-hexane (10ml) was then added and allowed to cool to room temperature. The supernatant was decanted off, and residual solid triturated with diethyl ether (50ml), to yield a white solid (67mg, 37%).1H-NMR (CDCI3) delta 0.65-1.19 (3H, br m), 1.78-1.98 (2H, m), 2.20-2.40 (1 H, m), 2.40- 2.57 (1 H, m), 2.96-3.48 (1 H, m), 3.48-3.96 (3H, m), 4.21-5.01 (1 H, m), 7.28-7.31 (2H, m), 7.36-7.45 (3H, m), 7.81-7.89 (4H, m).MS ES+ve m/z 384 (M+H).The single enantiomers were isolated from the racemic 4-[3-ethyl-4-(phenylcarbonyl)-1-piperazinyl]sulfonyl}benzonitrile (53mg) via chiral preparative chromatography using the following conditions:- Column: Chiralpak IC (20mm x 250mm, 5mum)- Eluent: Heptane: Ethanol 50:50 v/v pump-mixed - Flow rate =17. Omls/min- U.V. Absorbance (S) 215nm- Autosampler injection (250mul of sample in 20%Heptane/30%EtOH/50%DMF on column)- lsocratic Run time = 30 minutesIsolated enantiomers were analysed via chiral analytical chromatography using the following conditions:- Chiralpak IC (4.6mm x 250mm, 5mum)- Heptane: Ethanol 50:50 v/v pump-mixed - Flow rate =1. Omls/min- U.V. Absorbance (at) 215nm- Autosampler injection (1 Omul of sample in mobile phase on column)- lsocratic Run time = 30 minutesIsolated compounds: Example 5a: Faster running enantiomer (4-[(3S)-3-ethyl-4-(phenylcarbonyl)-1- piperazinyl]sulfonyl}benzonitrile or 4-[(3R)-3-ethyl-4-(phenylcarbonyl)-1- piperazinyl]sulfonyl}benzonitrile, 16mg)Retention time 19.37min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | Example 55A tert-butyl (2R)-4-[(6-[5-(difluoromethyl)pyridin-2-yl]oxy}quinolin-2-yl)carbonyl]-2-ethylpiperazine-1-carboxylate The product from Example 14A (300 mg, 0.95 mmol) was subjected to the conditions described in Example 14B, substituting <strong>[393781-71-0](R)-tert-butyl 2-ethylpiperazine-1-carboxylate</strong> for tert-butyl piperazine-1-carboxylate to give the titled compound (470 mg, 97%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.5% | Example 16A tert-butyl (2R)-2-ethyl-4-[(6-[5-(trifluoromethyl)pyridin-2-yl]oxy}quinolin-2-yl)carbonyl]piperazine-1-carboxylate. The product from Example 1D (200 mg, 0.59 mmol) was subjected to the conditions described in Example 11, substituting <strong>[393781-71-0](R)-tert-butyl 2-ethylpiperazine-1-carboxylate</strong> for 4-(piperidin-4-yl)morpholine to give the titled compound (238 mg, 67.5%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 85.0℃; for 12.0h; | To a solution of 1-(6-chloro-3-pyridyl)ethanone (4.00 g, 24.9 mmol; CAS36357-38-7) in ACN (8 mL) was added DIPEA (9.67 g, 74.8 mmol) and <strong>[393781-71-0](±)-tert-butyl 2-ethylpiperazine-1-carboxylate</strong> (6.41 g, 29.9 mmol; CAS393781-71-0). The reaction mixture was stirred at 85 C. for 12 hours. On completion, the reaction mixture was concentrated in vacuo to give a residue. The residue was purified by column chromatography (petroleum ether:ethyl acetate=30:1 to 5:1) to give the title compound (8.30 g, 100% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) delta 8.75 (d, J=2.0 Hz, 1H), 8.03 (dd, J=2.4, 9.2 Hz, 1H), 6.58 (d, J=8.8 Hz, 1H), 4.34 (d, J=13.2 Hz, 1H), 4.27 (d, J=10.4 Hz, 1H), 4.13 (q, J=7.2 Hz, 1H), 4.02 (s, 1H), 3.27 (dd, J=4.0, 13.2 Hz, 1H), 3.20-3.04 (m, 2H), 2.51 (s, 3H), 1.63-1.50 (m, 2H), 1.49 (s, 9H), 0.90 (t, J=7.2 Hz, 3H). |
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