Structure of 91419-53-3
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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. : | 91419-53-3 |
Formula : | C11H18N2O2 |
M.W : | 210.27 |
SMILES Code : | C(=O)(OC(C)(C)C)N1CCCC(C1)C#N |
MDL No. : | MFCD01861222 |
InChI Key : | UEFZTXGFHKPSFS-UHFFFAOYSA-N |
Pubchem ID : | 2756785 |
GHS Pictogram: |
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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 | 0.82 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 61.15 |
TPSA ? Topological Polar Surface Area: Calculated from |
53.33 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.52 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.32 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.78 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.05 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.06 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.54 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.78 |
Solubility | 3.51 mg/ml ; 0.0167 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.04 |
Solubility | 1.91 mg/ml ; 0.0091 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.37 |
Solubility | 9.05 mg/ml ; 0.0431 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 |
-6.65 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) |
2.74 |
* 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 |
---|---|---|
100% | With pyridine; trichlorophosphate; at 0 - 20℃; | 3(B) 3-Cyano-piperidine-1-carboxylic acid tert-butyl ester Phosphorus oxychloride (0.64 mL, 6.89 mmol) was added dropwise at 0 C. to a solution of <strong>[91419-49-7]3-carbamoyl-piperidine-1-carboxylic acid tert-butyl ester</strong> (1.58 g, 6.89 mmol) in pyridine (15 mL), under nitrogen atmosphere. After stirring overnight at room temperature, ethyl acetate was added and the solution was washed with 10% HCl (2 times). The phases were separated and the organics were dried over sodium sulphate and evaporated to dryness under reduced pressure. The title compound was used for the next step without further purification. Yield: quantitative; LCMS (RT): 4.48 min (Method A); MS (ES+) gave m/z: 211.1. |
100% | With phosphorus pentoxide; In pyridine; at 0 - 20℃; | Phosphorus oxychloride (0.64 mL, 6.89 mmol) was added dropwise at 0C to a solution of S-carbamoyl-piperidine-l-carboxylic acid tert-butyl ester (1.58 g, 6.89 mmol) in pyridine (15 mL), under nitrogen atmosphere. After stirring overnight at room temperature, ethyl acetate was added and the solution was washed with 10% HCl (2 times). The phases were separated and the organics were dried over sodium sulphate and evaporated to dryness under reduced pressure. The title compound was used for the next step without further purification. Yield: quantitative; LCMS (RT): 4.48 min (Method A); MS (ES+) gave m/z: 211.1 (MH+). |
87% | With triethylamine; trifluoroacetic anhydride; In dichloromethane; at 20℃; for 16h; | Tert-butyl 3-cyanopiperidine-l-carboxylate (3). To a solution of tert-butyl-3- carbamoyl piperidine-l-carboxylate 2 (1.0 g, 4 mmol) in anhydrous dichloromethane (20 mL), triethylamine (3.1 g, 31.0 mmol) was added followed by the dropwise addition of trifluoroaceticanhydride (4.1 g, 20.0 mmol). The resulting mixture was warmed to room temperature and stirred for 16 h. The reaction mixture was partitioned between dichloromethane (50 mL) and water (50 mL). The organic phase was washed with saturated bicarbonate solution (100 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield 3 (800 mg, 87%) as a thick liquid. 1H NMR (400 MHz, CDC13) delta 1.49 (s, 9H), 1.77 (m, 2H), 1.97 (brs, 1H), 2.66 (m, 1H), 3.35-3.84 (brs, 4H), |
53% | Step 3. Tert-butyl 3-cyanopiperidine-1-carboxylate; A 250-mL 3-necked round-bottomed flask was charged with a solution of <strong>[91419-49-7]tert-butyl 3-carbamoylpiperidine-1-carboxylate</strong> (5 g, 21.49 mmol, 1.00 equiv, 98%) in pyridine (50 mL). To this solution, POCl3 (5 g, 32.24 mmol, 1.50 equiv, 98%) was added drop wise at 0 C. and allowed to stir at 0 C. for 1 hour. The progress was monitored by TLC (EA:PE=1:1). The pyridine was removed by distillation. The mixture was diluted with H2O (40 mL) and pH was adjusted to 8 by addition of aqueous NaHCO3. Then, the resulting mixture was extracted with ethyl acetate (3×30 mL). Combined organic layers were dried over anhydrous sodium sulfate, filtered off and concentrated on a rotary evaporator. The crude was purified by distillation under reduced pressure (30 mm Hg) and the fractions collected at 40 C. to afford tert-butyl 3-cyanopiperidine-1-carboxylate as yellow oil (2.6 g, 53%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With lithium aluminium tetrahydride; In tetrahydrofuran; diethyl ether; at -78 - 27℃; for 0.5h; | A solution of tert-butyl 3-cyanopiperidine-1-carboxylate 62 (5.0 g, 23.00 mmol) in Ether (40 mL) was cooled to -78°C followed by drop wise addition of LAH (2.40 M solution in THF, 19.80 ml, 47.0 mmol). The resulting solution was then stirred for 30 mm. at RT. Reaction was monitored by TLC, reaction mixture was quenched with saturated NaOH solution at 0°C & reaction mixture was filtered through sodium sulfate, combined organic extracts were dried over Na2SO4 and concentrated to obtain crude compound (3.50 g, quantitative yield), which was carried forward as such for the next step. MS: 215.17 (M+H). |
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