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Chemical Structure| 42538-31-8 Chemical Structure| 42538-31-8

Structure of L-Orinithine lactam HCl
CAS No.: 42538-31-8

Chemical Structure| 42538-31-8

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Product Details of [ 42538-31-8 ]

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

Safety of [ 42538-31-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 42538-31-8 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

55.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

-0.05
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

-0.36
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

-0.41
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

0.13
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.14

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-0.74
Solubility 27.3 mg/ml ; 0.181 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-0.66
Solubility 33.2 mg/ml ; 0.22 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.56
Solubility 41.3 mg/ml ; 0.274 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-7.25 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.57

Application In Synthesis of [ 42538-31-8 ]

* 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.

  • Upstream synthesis route of [ 42538-31-8 ]

[ 42538-31-8 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 3184-13-2 ]
  • [ 42538-31-8 ]
YieldReaction ConditionsOperation 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.
References: [1] Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 247 - 250.
[2] Enantiomer, 2001, vol. 6, # 5, p. 275 - 279.
[3] Chemistry Letters, 1981, p. 1691 - 1694.
[4] Organic Process Research and Development, 2005, vol. 9, # 5, p. 570 - 576.
  • 2
  • [ 40216-82-8 ]
  • [ 42538-31-8 ]
YieldReaction ConditionsOperation 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)
References: [1] Journal of the Chemical Society, Dalton Transactions: Inorganic Chemistry (1972-1999), 1987, p. 1127 - 1132.
[2] Chemistry Letters, 1981, p. 1691 - 1694.
[3] Organic Process Research and Development, 2005, vol. 9, # 5, p. 570 - 576.
[4] Heterocycles, 2017, vol. 94, # 5, p. 964 - 978.
  • 3
  • [ 92235-39-7 ]
  • [ 42538-31-8 ]
References: [1] Journal of Medicinal Chemistry, 1988, vol. 31, # 7, p. 1430 - 1436.
[2] Patent: WO2004/22536, 2004, A1, . Location in patent: Page 85.
[3] Patent: WO2004/22536, 2004, A1, . Location in patent: Page 86.
[4] Patent: WO2004/22536, 2004, A1, . Location in patent: Page 87.
[5] Patent: WO2004/22536, 2004, A1, . Location in patent: Page 88.
  • 4
  • [ 2480-95-7 ]
  • [ 42538-31-8 ]
References: [1] Journal of Medicinal Chemistry, 1988, vol. 31, # 7, p. 1430 - 1436.
  • 5
  • [ 78397-39-4 ]
  • [ 42538-31-8 ]
References: [1] Journal of Medicinal Chemistry, 1988, vol. 31, # 7, p. 1430 - 1436.
 

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