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Chemical Structure| 3401-36-3 Chemical Structure| 3401-36-3

Structure of Z-Ala-OSu
CAS No.: 3401-36-3

Chemical Structure| 3401-36-3

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Product Details of [ 3401-36-3 ]

CAS No. :3401-36-3
Formula : C15H16N2O6
M.W : 320.30
SMILES Code : O=C(OCC1=CC=CC=C1)N[C@@H](C)C(ON2C(CCC2=O)=O)=O
English Name :2,5-Dioxopyrrolidin-1-yl ((benzyloxy)carbonyl)-L-alaninate
MDL No. :MFCD00053548
InChI Key :OFIYNISEFIEQBC-JTQLQIEISA-N
Pubchem ID :837751

Safety of [ 3401-36-3 ]

Computational Chemistry of [ 3401-36-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 23
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 8
Num. H-bond acceptors 6.0
Num. H-bond donors 1.0
Molar Refractivity 80.72
TPSA ?

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

102.01 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.83
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

0.87
Log Po/w (WLOGP)?

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

0.38
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.

0.89
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

0.69
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.93

Water Solubility

Log S (ESOL):?

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

-2.04
Solubility 2.93 mg/ml ; 0.00914 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.

-2.6
Solubility 0.812 mg/ml ; 0.00253 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

-2.87
Solubility 0.432 mg/ml ; 0.00135 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

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.

-7.64 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<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)

3.53

Application In Synthesis of [ 3401-36-3 ]

* 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 [ 3401-36-3 ]

[ 3401-36-3 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 1142-20-7 ]
  • [ 57296-03-4 ]
  • [ 3401-36-3 ]
YieldReaction ConditionsOperation in experiment
With pyridine In acetonitrile for 5h;
  • 2
  • [ 83056-79-5 ]
  • [ 3401-36-3 ]
  • [ 117560-20-0 ]
YieldReaction ConditionsOperation in experiment
With potassium <i>tert</i>-butylate 1) THF, -50 deg C, 10 min, 2) THF, -30 to -20 deg C, 30 min; Yield given. Multistep reaction;
  • 3
  • [ 3401-36-3 ]
  • [ 147-85-3 ]
  • [ 21027-01-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; triethylamine In 1,2-dimethoxyethane; water 5.A (A) (A) The Preparation of the Starting Material N-Benzyloxycarbonyl-L-alanyl-L-proline 289 g (0.903 mol) of N-benzyloxycarbonyl-L-alanine N-hydroxysuccinimide ester were dissolved in 1800 ml of 1,2-dimethoxyethane and to this solution was added a solution of 103.98 g (0.903 mol) of L-proline in 1350 ml of water followed by 267 ml (1.8 mol) of triethylamine. The mixture was stirred for 16 hours at room temperature and then the dimethoxyethane was removed by evaporation. The aqueous solution was then extracted twice with 300 ml of ethyl acetate each time and the organic layers were discarded. The remaining solution was acidified to pH 1-2 using concentrated hydrochloric acid and extracted twice with 900 ml of ethyl acetate each time. The organic layers were combined and washed twice with 400 ml of water each time, then dried over sodium sulphate, filtered and evaporated to an oil. On trituration with 1600 ml of ether, the product crystallized out and was filtered off, washed with ether and dried to yield 193.8 g of N-benzyloxycarbonyl-L-alanyl-L-proline of melting point 124°-125° C. A second crop of 27.6 g (melting point 123°-124° C.) was obtained by evaporation of the mother liquors, trituration with 300 ml of ether and storage at 4° C. for 1 hour; total yield 77%; [α]D20 =-91.2° (c=1.03% in methanol). Analysis for C16 H20 O5 N2 (320.35) Calculated: C: 60.00; H: 6.29; N: 8.74. Found: C: 59.91; H: 6.40; N: 8.85.
With hydrogenchloride; triethylamine In 1,2-dimethoxyethane; water 3.A EXAMPLE 3 (A) The preparation of the starting material: N-Benzyloxycarbonyl-L-alanyl-L-proline 289 g (0.903 mol) of N-benzyloxycarbonyl-L-alanine N-hydroxysuccinimide ester were dissolved in 1800 ml of 1,2-dimethoxyethane and to this solution was added a solution of 103.98 g (0.903 mol) of L-proline in 1350 ml of water followed by 267 ml (1.8 mol) of triethylamine. The mixture was stirred for 16 hours at room temperature and then the dimethoxyethane was removed by evaporation. The aqueous solution was then extracted twice with 300 ml of ethyl acetate each time and the organic layers were discarded. The remaining solution was acidified to pH 1-2 using concentrated hydrochloric acid and extracted twice with 900 ml of ethyl acetate each time. The organic layers were combined and washed twice with 400 ml of water each time, then dried over sodium sulphate, filtered and evaporated to an oil. On trituration with 1600 ml of ether, the product crystallized out and was filtered off, washed with ether and dried to yield 193.8 g of N-benzyloxycarbonyl-L-alanyl-L-proline of melting point 124°-125° C. A second crop of 27.6 g (melting point 123°-124° C.) was obtained by evaporation of the mother liquors, trituration with 300 ml of ether and storage at 4° C. for 1 hour; total yield 77%; [α]D20 =-91.2° (c=1.03% in methanol). Analysis for C16 H20 O5 N2 (320.35): Calculated: C: 60.00; H: 6.29; N: 8.74. Found: C: 59.91; H: 6.40; N: 8.85.
Stage #1: <i>L</i>-proline With tetra(n-butyl)ammonium hydroxide; potassium carbonate In 1,4-dioxane for 0.25h; Stage #2: (N-benzyloxycarbonyl)-L-alanine N-hydroxysuccinimide ester In 1,4-dioxane for 10h; General procedure: N-Protected dipeptide carbonitrileswere used in the present work both as such and asprecursors for the synthesis of other compounds understudy. The general procedure for the synthesis of thesecompounds is depicted in Fig. 5.
  • 4
  • [ 41036-32-2 ]
  • [ 3401-36-3 ]
  • [ 132343-11-4 ]
  • 5
  • [ CAS Unavailable ]
  • [ 3401-36-3 ]
  • [ 33628-84-1 ]
YieldReaction ConditionsOperation in experiment
In chloroform at 20℃; for 1h;
  • 6
  • [ 3989-97-7 ]
  • [ 3401-36-3 ]
  • [ 76264-12-5 ]
YieldReaction ConditionsOperation in experiment
800.0 mg With triethylamine In N,N-dimethyl-formamide at 0 - 20℃;
  • 7
  • [ 56-85-9 ]
  • [ 3401-36-3 ]
  • [ 21467-17-4 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In tetrahydrofuran; water P.A.1.1 1. 1. Preparation of Z-Ala-Gln-OH To a solution of 4.80 g of Z-Ala-OSu in 60 ml of tetrahydrofuran was added a solution of 2.19 g of H-Gln-OH in 40 ml of water and 2.10 ml of triethylamine and the mixture was stirred at a room temperature for 20 hours. Tetrahydrofuran and water were removed by distillation and the residue thus obtained was extracted with n-butanol. The n-butanol extract was washed with a 2%-acetic acid and butanol was removed by distillation. The precipitated substance thus obtained was collected by filtration and reprecipitated with methanol-ethyl acetate to obtain 3.87 g of Z-Ala-Gln-OH.
  • 8
  • [ 7087-68-5 ]
  • [ 3401-36-3 ]
  • [ 448949-65-3 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
In dichloromethane at 0℃; for 12h;
 

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