Structure of 50541-93-0
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 50541-93-0 |
Formula : | C12H18N2 |
M.W : | 190.28 |
SMILES Code : | C2=C(CN1CCC(N)CC1)C=CC=C2 |
MDL No. : | MFCD00006504 |
InChI Key : | YUBDLZGUSSWQSS-UHFFFAOYSA-N |
Pubchem ID : | 415852 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 62.85 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.26 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.26 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.37 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.08 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.74 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.76 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.64 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.07 |
Solubility | 1.63 mg/ml ; 0.00855 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.59 |
Solubility | 4.92 mg/ml ; 0.0259 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.94 |
Solubility | 0.219 mg/ml ; 0.00115 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 |
-6.49 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) |
1.6 |
* 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 acetate; In ethanol; for 54h;Heating / reflux; | A mixture of <strong>[31872-62-5]4-methoxy-3-nitropyridine</strong> (4.34 g, 28.1 MMOL), 4-AMINO-1- benzypiperidine (6.01 g, 30.9 MMOL), and NaOAc (2.31 g, 28.1 MMOL) in absolute ethanol (20 mL) was stirred at reflux for 54 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was dissolved in CH2CI2 (100 mL) and washed with water (2 x 30 mL). The organic layer was dried over anhydrous MgS04 and concentrated in vacuo to provide the product (8. 78 g) as a dark yellow solid. 1 H NMR (400 MHz, CDCI3) 5 9.21 (s, 1 H), 8.26 (dd, J = 6.0, 0. 4 Hz, 1 H), 8.20 (broad d, J = 7.1 Hz, 1 H), 7.34-7. 25 (complex m, 5 H), 6.70 (d, J = 6.0 Hz, 1 H), 3.62-3. 53 (m, 1 H), 3.55 (s, 2 H), 2. 89-2. 79 (m, 2 H), 2.30-2. 20 (m, 2 H), 2.10-2. 00 (m, 2 H), 1.76-1. 65 (m, 2 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In isopropyl alcohol;Heating / reflux; | A mixture of methyl 2-bromopyrazine-3-carboxylate (J. Med. Chem. , 1969, 12, 285) (2.2 g, 10.1 mmol) and 4-AMINO-1-BENZYLPIPERIDINE (2.0 g, 10.5 mmol) was refluxed in 2- propanol overnight. Thin layer chromatography (10% methanol in ethyl acetate) showed the reaction was complete. The solvent was evaporated, and the crude product dissolved in chloroform (100 mL), which was washed with saturated sodium carbonate solution (20 ML), and dried over magnesium sulfate. The title compound was obtained as a gum (3.8 g). MS 327 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With hydrogenchloride; ammonia; In chloroform; water; | EXAMPLE 42 N-(1-benzyl-4-piperidyl)-1,4-benzodioxane-5-carboxamide hydrochloride 200 ml of chloroform and 50 g of 1-benzyl-4-amino piperidine were introduced into a balloon flask provided with an agitator and a thermometer, and then 50 g of <strong>[38871-41-9]1,4-benzodioxane-5-carbonyl chloride</strong> was added in portions at a temperature of from 5-10 C. After agitation of the mixture at ambient temperature the solvent was removed under vacuum and the residue was dissolved in 300 ml of water. After precipitation of the base by addition of ammonia, the water was removed and the resulting product was treated with a solution of hydrochloric acid. 75 g of N-(1-benzyl-4-piperidyl)-1,4-benzodioxane-5-carboxamide hydrochloride was produced (M.P.: 205 C.; yield: 77%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | To a solution of 4-(2,3-Epoxypropoxy)-carbazole (1 g, 4.1 mmol) in THF (30 mL) cooled to 5-10 0C, was added LiClO4 (0.44 g, 4.1 mmol) and the reaction mixture was stirred for 15 minutes. 4-Amino-l-benzylpipe?dine (1.26 mL, 6.2 mmol) was added dropwise to the above reaction mixture at room temperature and stirring was continued for 12 hours. To the reaction mixture 50 mL of saturated NH4Cl was added EPO <DP n="44"/>and stirring was continued for 5 minutes, subsequently the solution was extracted with dichloromethane (100 rnL), washed with water and brine solution. The organic layer was dried over anhydrous Na2SO4 and concentrated to afford the crude compound as light brown colored paste. The crude compound was purified by silica gel column chromatography, using DCM/MeOH (7:3) to afford the title compound as pale yellow colored solid (1.2 g, 65 % yield). | |
65% | Step 1: Preparation of 3-[(1-benzylpiperidin-4-yl)amino]-1-(9H-carbazol-4-yloxy)pro-pan-2-ol To a solution of 4-(2,3-Epoxypropoxy)-carbazole (1 g, 4.1 mmol) in THF (30 mL) cooled to 5-10 C., was added LiClO4 (0.44 g, 4.1 mmol) and the reaction mixture was stirred for 15 minutes. 4-amino-1-benzylpiperidine (1.26 mL, 6.2 mmol) was added dropwise to the above reaction mixture at room temperature and stirring was continued for 12 hours. To the reaction mixture 50 mL of saturated NH4Cl was added and stirring was continued for 5 minutes, subsequently the solution was extracted with dichloromethane (100 mL), washed with water and brine solution. The organic layer was dried over anhydrous Na2SO4 and concentrated to afford the crude compound as light brown colored paste. The crude compound was purified by silica gel column chromatography, using DCM/MeOH (7:3) to afford the title compound as pale yellow colored solid (1.2 g, 65% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75%; 21% | With triethylamine; In tetrahydrofuran; ethanol; for 12.0h;Reflux; | General procedure: The <strong>[151229-84-4]2,6-dichloropyridine-3,5-dicarbonitrile</strong>s 14 [27]-15 [28] were suspended in a mixture of THF/EtOH (2:1, v:v). Then, amine 22 or 24 [41] followed by triethylamine, were added. The mixture was then heated under reflux. After cooling, the solvent was removed in vacuo and the resulting crude submitted to flash column chromatography. |
75%; 21% | With triethylamine; In tetrahydrofuran; ethanol; at 20℃; | General procedure: 2,6-Dichloro-4-phenylpyridine-3,5-dicarbonitrile 13 or <strong>[151229-84-4]2,6-dichloropyridine-3,5-dicarbonitrile</strong> 14 was suspended in a mixture of THF/EtOH (2:1, v:v). The corresponding amines 9-12, followed by triethylamine, were then added. The mixture was then heated under reflux. After cooling, the solvent was removed in vacuum and the resulting crude submitted to flash column chromatography, to give compounds 1-8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Preparation Example 73 Synthesis of Compound 73 (0336) (0337) Hydroxybenzophenone 2, methyl chloroacetate and K2CO3 were mixed in acetone, refluxed and stirred to afford ester 3 (step a). After completion of the reaction, an aqueous NaOH solution was added thereto, followed by acidification with HCl to obtain carboxylic acid 4 (step b). Then, 4-amino-1-benzylpiperidine was added to the carboxylic acid 4, followed by conducting the reaction in the same manner as in the preparation example 12, using carbonyl diimidazole (CDI) as a condensing agent, to obtain Compound 73. (0338) 1H-NMR (600 MHz, DMSO-d6): delta 8.04 p.p.m. (d, j=8.0 Hz, 1H), 7.74 (d, J=9.1 Hz, 2H), 7.68 (d, J=7.1 Hz, 2H), 7.65 (t, j=7.6 Hz, 1H), 7.55 (t, j=5.8 Hz, 2H), 7.27-7.32 (m, 4H), 7.23 (t, J=7.1 Hz, 1H), 7.09 (d, J=9.0 Hz, 2H), 4.58 (s, 2H), 3.63 (m, 1H), 3.44 (s, 2H), 2.74 (d, J=11.7 Hz, 2H), 1.99 (t, J=11.5 Hz, 2H), 1.70 (d, J=9.8 Hz, 2H), 1.50 p.p.m. (dq, J1=3.0 Hz, J2=11.9 Hz, 2H); (0339) 13C-NMR (150 MHz, DMSO-d6): delta 194.4, 166.2, 161.5, 138.6, 137.7, 132.2, 132.0, 129.8, 129.3, 128.7, 128.5, 128.1, 126.8, 114.6, 66.9, 62.1, 51.9, 46.1, 31.4 |