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Chemical Structure| 3392-07-2 Chemical Structure| 3392-07-2

Structure of Boc-Gly-OSu
CAS No.: 3392-07-2

Chemical Structure| 3392-07-2

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Product Details of [ 3392-07-2 ]

CAS No. :3392-07-2
Formula : C11H16N2O6
M.W : 272.25
SMILES Code : O=C(OC(C)(C)C)NCC(ON1C(CCC1=O)=O)=O
MDL No. :MFCD00042761
InChI Key :LJCWRJYVPJJTMB-UHFFFAOYSA-N
Pubchem ID :76926

Safety of [ 3392-07-2 ]

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

Computational Chemistry of [ 3392-07-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 0
Fraction Csp3 0.64
Num. rotatable bonds 7
Num. H-bond acceptors 6.0
Num. H-bond donors 1.0
Molar Refractivity 65.89
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.

1.94
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

-0.04
Log Po/w (WLOGP)?

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

-0.26
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.

0.07
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

-0.24
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.29

Water Solubility

Log S (ESOL):?

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

-1.04
Solubility 24.8 mg/ml ; 0.091 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.

-1.65
Solubility 6.07 mg/ml ; 0.0223 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

-1.15
Solubility 19.3 mg/ml ; 0.071 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.

-7.99 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)

3.02

Application In Synthesis of [ 3392-07-2 ]

* 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 [ 3392-07-2 ]

[ 3392-07-2 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 3392-07-2 ]
  • [ 6893-02-3 ]
  • Boc-Gly-T3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Production of the drug substance Gly-T3 ' HCl was performed as a one-pot reaction inside a 20-gallon glass lined reactor. To limit exposure of the workers to the potent material, the starting reagent T3 was prepared as a slurry in THF inside an EPO <DP n="44"/>isolator. The resulting slurry was then transferred to the 20-gallon reactor through a Teflon line. Subsequently, Boc-Gly-OSu was dissolved in THF, transferred to the 20-gallon reactor and then DIEA was dissolved in THF, and also transferred to the 20-gallon reactor. The suspension was stirred for 15 hours, at ambient temperature and became a clear solution. In process testing by HPLC (% AUC) of the collected sample after 15 hours showed a purity of 98.5 % for the desired compound, Boc- Gly-T3. The reaction was then quenched by adding water and the THF was removed by distillation. The solvent, TBME was then added and the batch was allowed to stir overnight at 5 to 10 0C. The solution was acidified by a 20 % aqueous Na2SO4ZNaHSO4 buffer solution. The product was extracted in TBME and the organic layers were combined in a 60 L Pope tank and dried with Na2SO4. The dried solution was then filtered through a 0.22 mum filter, charged into the 20- gallon reactor and stirred overnight at 15 0C. The TBME was removed by distillation, followed by IPAc chases (continuous feed), while the batch stirred overnight at 15 0C. The intermediate was Boc deprotected by pressurizing the 20- gallon reactor headspace with 30 psi HCl gas for 3 hours and 30 minutes. The obtained precipitate was filtered inside the isolator, washed with IPAc, and dried for 110 hours inside a vacuum oven at 35 0C. In process testing by GC showed the presence of 6.13 % residual IPAc. Therefore, the solids were hydrated (water displacement) for approximately 24 hours and dried until constant weight, in a vacuum oven for 50 hours at 35 0C. The material was packaged in glass amber bottles, which were put in polyethylene bags and stored at - 20 0C with desiccants.
 

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