Structure of L-Orinithine lactam HCl
CAS No.: 42538-31-8
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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. : | 42538-31-8 |
Formula : | C5H11ClN2O |
M.W : | 150.61 |
SMILES Code : | O=C1NCCC[C@@H]1N.[H]Cl |
MDL No. : | MFCD09259964 |
InChI Key : | NLAYLURYAOXTTE-WCCKRBBISA-N |
Pubchem ID : | 45789910 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.8 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 40.62 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.05 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.36 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.41 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.13 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.14 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.74 |
Solubility | 27.3 mg/ml ; 0.181 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.66 |
Solubility | 33.2 mg/ml ; 0.22 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.56 |
Solubility | 41.3 mg/ml ; 0.274 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 |
No |
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 |
-7.25 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) |
1.57 |
* 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 |
---|---|---|
97% | Stage #1: With chloro-trimethyl-silane In methanol at 20℃; for 12 h; Stage #2: With sodium ethanolate In methanol; ethanol at 0 - 20℃; for 0.583333 h; |
Trimethylchlorosilane (2.8 mL, 23 mmol, 4 equiv) was added to L-ornithine·HCl (1.0 g,6.0 mmol, 1 equiv) followed by the addition of anhydrous methanol (20 mL). The mixturestirred at rt for 12 h. The solution was then cooled to 0 °C and a 21percent (w/w) solution ofsodium ethoxide in ethanol (42 mmol, 17 mL) was added; after 5 min the solution wasallowed to warm to rt and stirred for another 30 min. The solution was neutralized to pH7 with 6 N aq HCl. The resulting solution was filtered and conc. in vacuo. Salts wereremoved by dissolution in isopropanol, filtered, and conc. in vacuo. The crude residuewas purified by flash column chromatography on silica gel (30percent methanol indichloromethane) to afford lactam hydrochloride 4 as a hygroscopic, pale yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
131.2 g | Stage #1: With sodium methylate In methanol at 0 - 20℃; for 2 h; Inert atmosphere Stage #2: With hydrogenchloride In methanol |
L-Ornithine hydrochloride (180 g, 1.07 mol) dissolvedin MeOH (1800 mL) was stirred for 30 min at 0 C under Ar. Thionyl chloride (160 mL, 2.19 mol) wasadded dropwise over 40 min at 0 C. The solution was stirred for 30 min at 0 C and refluxed for 6 h, andthen solvent was removed in vacuo to give methyl L-ornithinate dihydrochloride (232.1 g). MethylL-ornithinate dihydrochloride (223 g, 1.02 mol) dissolved in MeOH (2500 mL) was stirred at 0 C underAr. NaOMe (116 g, 2.15 mol) was added, and the solution was stirred for 2 h at room temperature. Afterremoval of the solvent in vacuo, the residue dissolved in Et2O (600 mL) was stirred at room temperature.After filtration through celite, the solvent was removed in vacuo. The residue was dissolved in MeOH(400 mL), and then MeOH saturated with HCl (100 mL) was added to give the crude product.Recrystallization from MeOH-isopropyl alcohol (1:1) provided (S)-3-aminopiperidin-2-one hydrochloride(2: 131.2 g, yield 86percent) |
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