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Structure of 298716-03-7

Chemical Structure| 298716-03-7

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Product Details of [ 298716-03-7 ]

CAS No. :298716-03-7
Formula : C11H17NO4
M.W : 227.26
SMILES Code : O=C(N[C@H]1C=C[C@H](C(O)=O)C1)OC(C)(C)C
MDL No. :MFCD12405610
InChI Key :WOUNTSATDZJBLP-YUMQZZPRSA-N
Pubchem ID :7168126

Safety of [ 298716-03-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Computational Chemistry of [ 298716-03-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 0
Fraction Csp3 0.64
Num. rotatable bonds 5
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 58.69
TPSA ?

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

75.63 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.04
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

1.25
Log Po/w (WLOGP)?

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

1.54
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.

0.93
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

0.14
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.18

Water Solubility

Log S (ESOL):?

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

-1.71
Solubility 4.47 mg/ml ; 0.0197 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.

-2.44
Solubility 0.832 mg/ml ; 0.00366 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

-0.67
Solubility 48.4 mg/ml ; 0.213 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.

-6.8 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.

0.56

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)

3.79

Application In Synthesis of [ 298716-03-7 ]

* 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 [ 298716-03-7 ]

[ 298716-03-7 ] Synthesis Path-Downstream   1~5

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  • [ 1312161-65-1 ]
  • [ 151907-79-8 ]
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  • 3
  • [ 168683-02-1 ]
  • [ 1312161-65-1 ]
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  • [ 298716-03-7 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 3: Epimerisation of (1 S,4R)-methyl 4-(te/f-butoxycarbonyl)amino cyclopent-2-enecarboxylate, 11.11 11+12 13A methanol solution of 11 (10 L, containing about 23.63 mol) is cooled to - 2C. A solution of sodium methoxide (127.6 g, 2.36 mol) in methanol (700 mL) is added over 30 minutes, at a rate that maintains the reaction temperature at 00C or less. After 50 minutes, gas chromatography (GC) analysis indicates a product distribution of 43% compound 12, 54% compound 11 , and 3% compound 13.Acetic acid (140 mL) is added over 5 minutes, the mixture is allowed to warm to 100C, then the mass is concentrated. After 7 L of solvent has been removed, the concentrated mixture is diluted with water (2 L) and MTBE (10 L).The aqueous layer is extracted with further MTBE (1 L). The combined organic layers are concentrated to give the products 11+12+13 in a MTBE solution, with a total volume of 7.5 L.A sample (2 mL) is removed from the bulk and concentrated further, and this is found to contain 1.5 g of product and therefore 7.5 L should contain 5.625 kg, (99% mass recovery).GC analysis shows the material to be 44% compound 12, 52% compound11 , and 4% compound 13.trans Diastereoismer 12; 1H NMR (400MHz, MeOH): delta 5.91 -5.87 (1 H, m),5.85-5.81 (1 H, m), 4.74 (1 H, brs), 3.75-3.72 (1 H, m) 3.66, (3H, s), 2.60-2.49 (1 H, m), 1.89-1.78 (1 H, m), 1.46 (9H, s). cis Diastereoismer 11 ; 1H NMR (400MHz, MeOH): delta 5.91 -5.87 (1 H, m), 5.85-5.81 (1 H, m), 4.65 (1 H, brs), 3.72, (3H, s), 3.57-3.52 (1 H, m), 2.60-2.49 (1 H, m), 1.89-1.78 (1 H, m), 1.46 (9H, s). EXAMPLE 4: Ester hydrolysis.A solution of a mixture of methyl esters 11+12+13 in MTBE (3.5 L, containing about 11.0 mol) is diluted with methanol (4 L) under N2, then cooled to -3.5C (jacket temperature -5C). A solution of lithium hydroxide monohydrate (508 g, 12.08 mol) in water (2.5 L) is added over 5.5 hours with the reaction temperature being kept below 2C at all times during the addition. Once the addition is complete, the mass is stirred for at 2C for 30 minutes, then at 100C for 16 hours.The mass is neutralised with 6 M HCI and concentrated. After 4 L of solvent has been removed, the concentrated mixture is acidified to pH 3 by the addition of further 6M HCI. The acidic mixture is extracted with ethyl acetate (10 L, then 2.5 L), and the combined organics are washed with brine (2*1.5 L), then concentrated. Toluene (2*2.5 L) is added during the concentration to aid the removal of water. The products 14+15+16 are recovered as an off white solid (2.67 kg, 94% yield).trans Diastereoismer 15; 1H NMR (400MHz, MeOH): delta 5.93-5.90 (1 H, m), 5.84-5.83 (1 H, m), 4.75 (1 H, brs), 3.72-3.67 (1 H, m), 2.59-2.49 (1 H, m), 1.90-1.78 (1 H, m), 1.45 (9H, s).cis Diastereoismer 14; 1H NMR (400MHz, MeOH): delta 5.93-5.90 (1 H, m), 5.84-5.83 (1 H, m), 4.67 (1 H, brs), 3.52-3.48 (1 H, m), 2.59-2.49 (1 H, m), 1.90-1.78 (1 H, m), 1.45 (9H, s).
  • 4
  • [ 151792-53-9 ]
  • [ 1312161-65-1 ]
  • [ 151907-79-8 ]
  • [ 298716-03-7 ]
  • 5
  • [ 79200-56-9 ]
  • [ 1312161-65-1 ]
  • [ 151907-79-8 ]
  • [ 298716-03-7 ]
 

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