Structure of 859518-32-4
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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. : | 859518-32-4 |
Formula : | C15H22N2O2 |
M.W : | 262.35 |
SMILES Code : | O=C(N1[C@H](C2=CC=CC=C2)CNCC1)OC(C)(C)C |
MDL No. : | MFCD04972241 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 19 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.53 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 82.99 |
TPSA ? Topological Polar Surface Area: Calculated from |
41.57 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.96 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.98 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.48 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.93 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.83 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.04 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.68 |
Solubility | 0.544 mg/ml ; 0.00207 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.48 |
Solubility | 0.871 mg/ml ; 0.00332 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.57 |
Solubility | 0.0713 mg/ml ; 0.000272 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) |
Yes |
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 |
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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.61 |
* 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 t-butanolate;palladium diacetate; 2-(dicyclohexylphosphino)-2'-methylbiphenyl; In 1,2-dimethoxyethane; at 95.0℃; for 16.0h; | A mixture of 3-(6-bromo-2-pyridyl)-l-trityl-pyrazolo[5,4-b]pyridine (100 mg, 0.1933 mmol) and (2S)-2-pheny]piperazine (54.56 mg, 0.2320 mmol) in DME (2.500 mL) was treated with sodium t-butoxide (27.87 mg, 0.2900 mmol) followed by dicyclohexyl-[2-(o-tolyl)phenyl]phosphane (7.046 mg, 0.01933 mmol) and Palladium acetate (4.340 mg, 0.01933 mmol). The mixture was allowed to stir at 95 degrees in a sealed tube overnight. The mixture was allowed to cool, filtered through celite and concentrated to give a yellow oil. This was taken up in DCM (6ml) and cooled to 0 0C. Triethylsilane (0.12 mL) and TFA (1 mL) were added and the reaction stirred at O0C for 1 hour. The solvent was removed in vacuo and the residue purified by reverse phase preparative HPLC [Waters Sunfire C 18, lOuM, IOOA column, gradient 10% - 95%B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as a white solid (20mg, 29% Yield).ES+ 357, IH NMR (400.0 MHz, MeOH) d 8.89 (dd, J = 1.6, 8.1 Hz, IH), 8.53 (dd, J = 1.6, 4.6 Hz, I H), 7.70 - 7.66 (m, I H), 7.55 (dd, J = 4.7, 7.3 Hz, 3H), 7.46 - 7.42 (m, 2H), 7.38 - 7.34 (m, IH), 7.20 (dd, J = 4.6, 8.1 Hz, I H), 6.87 (d, J = 8.4 Hz, IH), 4.56 (s, I H), 4.55 (dd, J = 1.3, 12.7 Hz, I H), 4.42 - 4.39 (m, IH), 3.98 (dd, J = 3.0, 10.7 Hz, IH), 3.29 - 3.25 (m, IH) and 3.20 - 2.97 (m, 3H) ppm |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium carbonate; In acetonitrile; at 20.0℃; for 16.0h; | To a solution of <strong>[859518-32-4]tert-butyl (R)-2-phenylpiperazine-1-carboxylate</strong> (0.30 g, 1.14 mmol) in acetonitrile (6.0 mL) was added 2,2,2-trifluoroethyl trifluoromethanesulfonate (0.33 mL, 2.29 mmol) and potassium carbonate (0.32 g, 2.29 mmol). After stirring at ambient temperature for 16 h, the reaction was diluted with ethyl acetate (20 mL) and water (20 mL). The aqueous layer was removed and the organic layer was washed with water (10 mL), brine (10 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness to afford the title compound as a colorless oil (0.389 g, 99% yield). MS (ES+) m/z 345.1 (M + 1). 1H NMR (300 MHz, CDCl3) δ 7.53-7.50 (m, 2H), 7.36-7.27 (m, 3H), 5.27-5.26 (m, 1H), 3.92-3.87 (m, 1H), 3.48-3.42 (m, 111), 3.06-2.96 (m, 3H), 2.90-2.8 1 (m, 2H), 2.58-2.50 (m, 1H), 1.48 (s, 9H); 19F NMR (282 MHz, CDCl3): δ -68.6 (s, 3F). |
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