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Chemical Structure| 5211-23-4 Chemical Structure| 5211-23-4

Structure of Cbz-Pro-OMe
CAS No.: 5211-23-4

Chemical Structure| 5211-23-4

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Synonyms: Methyl(S)-N-(benzyloxycarbonyl)prolinate; N-Z-L-proline methyl ester

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Product Details of [ 5211-23-4 ]

CAS No. :5211-23-4
Formula : C14H17NO4
M.W : 263.29
SMILES Code : O=C(N1[C@H](C(OC)=O)CCC1)OCC2=CC=CC=C2
Synonyms :
Methyl(S)-N-(benzyloxycarbonyl)prolinate; N-Z-L-proline methyl ester
MDL No. :MFCD00134246
InChI Key :BLQYEDXWEDWCNJ-LBPRGKRZSA-N
Pubchem ID :688168

Safety of [ 5211-23-4 ]

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

Computational Chemistry of [ 5211-23-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 6
Fraction Csp3 0.43
Num. rotatable bonds 6
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 72.71
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

55.84 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.85
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

1.74
Log Po/w (WLOGP)?

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

1.43
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.

1.57
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

1.55
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.83

Water Solubility

Log S (ESOL):?

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

-2.41
Solubility 1.03 mg/ml ; 0.00392 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-2.53
Solubility 0.778 mg/ml ; 0.00296 mol/l
Class?

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

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

-2.79
Solubility 0.432 mg/ml ; 0.00164 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

Yes
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

Yes
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.

-6.67 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

0.0
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

1.0 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<0.0
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)

2.84

Application In Synthesis of [ 5211-23-4 ]

* 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.

  • Downstream synthetic route of [ 5211-23-4 ]

[ 5211-23-4 ] Synthesis Path-Downstream   1~4

  • 2
  • [ 5672-83-3 ]
  • [ 5211-23-4 ]
  • [ 141406-83-9 ]
  • 3
  • [ 5672-83-3 ]
  • [ 5211-23-4 ]
  • 4
  • [ 186581-53-3 ]
  • [ 6216-63-3 ]
  • [ 5211-23-4 ]
YieldReaction ConditionsOperation in experiment
94% NaClO2 (498 mg, 5.507 mmol) was added to a mixed solution containing 150 mg (1.101 mmol) of 3-phenylpropanol in a CH2Cl2 (3.7 mL)-NaH2PO4 aqueous solution (2.1 mL, 0.52 M solution being 1.0 equivalent), followed by stirring. Then, Me-AZADO+Cl- (11.1 mg, 0.05507 mmol) was immediately added, followed by vigorous stirring at room temperature until disappearance of the starting material 3-phenylpropanol and its aldehyde product 3-phenylpropanal was confirmed. After completion of the reaction, 2-methyl-2-butene (1.17 mL, 11.01 mmol) was added under cooling with ice, and an aqueous layer and an organic layer were separated under a weakly acidic condition. To the organic layer, a 10percent sodium hydroxide aqueous solution was added to obtain a solution having a pH 11, from which organic substances other than the ionic carboxylic acid were extracted with diethyl ether. The remained aqueous layer was adjusted to pH 3 with 10percent hydrochloric acid, and from the aqueous layer, a molecular type carboxylic acid was extracted with diethyl ether. The organic layer was washed with an aqueous sodium chloride solution and then dried over magnesium sulfate, and the solvent was distilled off under reduced pressure.The residue was dissolved in methylene chloride, and diazomethane was added under cooling with ice, and after confirming the completion of a methyl esterification reaction, stirring was continued at room temperature for a while. Then, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 176 mg (yield: 97percent) of a methyl ester.Cases wherein the reaction was carried out in the same manner, are shown with respect to the case where Me-AZADO+Cl- was employed and the case where TEMPO+CL- was employed. Here, in the Table, "alcohol" represents the alcohol, "time (hr)" represents the reaction time (unit: hr), "yield (percent)" represents the yield (percent) which was calculated by the isolated yield of the methyl ester by the diazomethane. "note" represents a note, "trace" represents a trace amount, "Additive" represents an additive, "SASS" represents sodium stearate, and "slight chlorination" means that slight chlorination was observed. "Cat." represents the catalyst. TABLE 1 yield percent No. alcohol time [hr] note 1 1.5 77 97 2 1.5 63 93 3 10 trace 84 4 32 trace 86 5 5.5/6.5 trace 99/96Additive (5 mol percent) PhCO2II/ SASS* 6 4.5 20 91 7 10 25 90 8 24 <16 <84 slight chlorination 9 3 <13 <92 slight chlorination cat. 20 mol percent 10 5 - 92 11 1 - 88 12 15 trace 94 SASS*: Stearic Acid Sodium Salt
 

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