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Chemical Structure| 3392-05-0 Chemical Structure| 3392-05-0

Structure of Boc-Ala-Osu
CAS No.: 3392-05-0

Chemical Structure| 3392-05-0

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Product Details of [ 3392-05-0 ]

CAS No. :3392-05-0
Formula : C12H18N2O6
M.W : 286.28
SMILES Code : C[C@H](NC(OC(C)(C)C)=O)C(ON1C(CCC1=O)=O)=O
MDL No. :MFCD00065974
InChI Key :COMUWNFVTWKSDT-ZETCQYMHSA-N
Pubchem ID :11011585

Safety of [ 3392-05-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 3392-05-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 20
Num. arom. heavy atoms 0
Fraction Csp3 0.67
Num. rotatable bonds 7
Num. H-bond acceptors 6.0
Num. H-bond donors 1.0
Molar Refractivity 70.69
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.

2.13
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

0.36
Log Po/w (WLOGP)?

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

0.13
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.

0.35
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

-0.02
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.59

Water Solubility

Log S (ESOL):?

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

-1.38
Solubility 11.9 mg/ml ; 0.0417 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.

-2.07
Solubility 2.45 mg/ml ; 0.00857 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

-1.18
Solubility 19.1 mg/ml ; 0.0668 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.

-7.79 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)

3.67

Application In Synthesis of [ 3392-05-0 ]

* 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 [ 3392-05-0 ]

[ 3392-05-0 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 80143-17-5 ]
  • [ 3392-05-0 ]
  • [ 18814-49-8 ]
  • 3
  • [ 3392-05-0 ]
  • [ 147-85-3 ]
  • [ 33300-72-0 ]
YieldReaction ConditionsOperation in experiment
91.1% General procedure: Under argon protection, BSA (2.2equiv.) was added to a solution of amino acid (1.1equiv.) in anhydrous dichloromethane. After the mixture was stirred for 1-8h at 23C, a solution of N-Boc protected NHS ester (1equiv.) in dichloromethane was added. The reaction mixture was stirred at 23C under argon until all active ester was consumed as judged by TLC analysis. The reaction mixture was washed with brine, dried over Na2SO4 and concentrated in vacuo to provide a white solid. The isolated product was recrystallized from diethyl ether/n-hexane to yield the targeted dipeptide as a white solid.
80% Suspension 1.3 g (11 muetaetaomicronIota) of proline, 1.6 g (11 muiotaetaomicronIota) K2CO3 and 0.1 g of tetrabutylammonium hydroxide in 10 ml of dioxane are stirred for 15 min, 2.9 g (10 muiotatauiotaomicronIota) of N-oxysuccinimide ether of tert-butyloxycarbonyl-L-alanine are added and stirred for 10 h. Then they are diluted with water (25 ml) and stirred for 1 h, extracted with hexane-ether mixture (1 :1 , 15 ml), the aqueous solution is acidified with 1 M hydrochloric acid to pH 2-3, extracted with ethyl acetate (50 ml + 20 ml), the extract is washed with brine, dried with magnesium sulfate and boiled off. 2.3 g (80%) of chromatographically pure tert-butyloxycarbonylalanylproline with melting point of 155- 156C, Rf 0.47 (toluene - acetone - acetic acid, 100:50:1) is obtained, which is used for amide obtainment at the next stage without further purification.
  • 4
  • [ 4089-07-0 ]
  • [ 3392-05-0 ]
  • [ 76658-39-4 ]
  • 5
  • [ 3392-05-0 ]
  • [ 18814-49-8 ]
  • 6
  • [ 3468-18-6 ]
  • [ 3392-05-0 ]
  • tert-butyl (S)-(1-(((1H-indol-4-yl)methyl)amino)-1-oxopropan-2-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% In N,N-dimethyl-formamide; at 0 - 20℃; [0109j Boc-Ala-OSu (515 mg, 1.8 mmol) was dissolved in 10 mL dry dichloromethane.The solution was cooled to 0 C and a solution of <strong>[3468-18-6]4-(aminomethyl)indole</strong> (263 mg, 1.8 mmol) inDMF (2 mL) was added. The reaction mixture was warmed to room temperature and stirred overnight. After completion of reaction, dichloromethane was evaporated. The crude solid was dissolved in ethyl acetate and washed with water followed by brine. The organic layer was dried over anhydrous sodium sulfate and evaporated to give product (560 mg, 98%), which was pure byNMR. ?H NMR (500 MHz, DMSO-d6) oe 11.11 (s, 1H), 8.17 (t, J= 5.8 Hz, 1H), 7.32-7.29(m, 2H), 7.01 (t, J= 7.6 Hz, 1H), 6.90 - 6.87 (m, 2H), 6.48 - 6.47 (m, 1H), 4.58 (dd, J 15.2,6.0 Hz, 1H), 4.47 (dd, J 15.2, 5.5 Hz, 1H), 4.05 - 3.99 (m, 1H), 1.38 (s, 9H), 1.20 (d, J= 7.1 Hz, 3H).
  • 7
  • [ 18800-73-2 ]
  • [ 3392-05-0 ]
  • [ 18814-49-8 ]
YieldReaction ConditionsOperation in experiment
29.4 g 30 g (1.0eq) Boc-D-Glu(OBzl)-NH2 was dissolved in 100 mL trifluoroacetic acid-dichloromethane (v/v=1:1),and the solution was stirred for 1 hour at r.t to removed Boc group. After the completion of the reaction, the TFA wasremoved under vacuum; the residue was repeatedly grinded in anhydrous ether, washed, and evaporated to dryness,and re-dissolved in tetrahydrofuran. The pH of the solution was adjusted to 7?8 with N-methyl morpholine (NMM) in icebath. The Boc-Ala-OSu solution was sparingly added to the solution in a few portions. The mixture was stirred for 5hours in ice bath, and continued for 24 hours at r.t after the completion of the reaction, the mixture was evaporated todryness. The residue was dissolved in proper amount AcOEt and successively washed with diluted hydrochloric acid,saturated sodium bicarbonate aqueous solution and water. The AcOEt layer was separated, and dried with MgSO4overnight. The mixture was filtered and the filtrate was evaporated to dryness. The residue was recrystallized frommethanol and water, the crystal was washed with a big amount of ether to obtained 29.4 g target compound. Yield: 81%,m.p.=134?135 C 1H-NMR(300MHz, DMSO-d6): 1.36(9H, br.s,.1-H), 7.92(1H, d, J=7.8Hz, 4-H), 4.17(1H, m, 5-H), 1.15(3H, d, J=7.2Hz, 6-H), 7.10(1H, d, J=6.6Hz, 8-H), 3.91(1H, m, 9-H), 7.18(1H, br.s, 11-Ha), 7.31(1H, br.s, 11-Hb), 1.75(1H, m,12-Ha), 2.03(1H, m, 12-Hb), 2.33(2H, t, J=7.5Hz, 13-H), 5.07(2H, s, 15-H), 7.31-7.40(5H, m, 17?21-H). ESI-MS: 408.71 [M+H]+, 815.44 [2M+H]+.HR-MS(TOF): 408.2137 [M+H]+, 430.1955 [M+Na]+, C20H29N3O6.
 

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