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Chemical Structure| 14002-73-4 Chemical Structure| 14002-73-4

Structure of 14002-73-4

Chemical Structure| 14002-73-4

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Product Details of [ 14002-73-4 ]

CAS No. :14002-73-4
Formula : C7H14O3
M.W : 146.18
SMILES Code : O=C(OCC)C(C)(C)CO
MDL No. :MFCD21643853
Boiling Point : No data available
InChI Key :JBDMHPJPFPMZLI-UHFFFAOYSA-N
Pubchem ID :274432

Safety of [ 14002-73-4 ]

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

Computational Chemistry of [ 14002-73-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 0.86
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 37.95
TPSA ?

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

46.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.02
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

0.66
Log Po/w (WLOGP)?

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

0.57
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.

0.75
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

0.66
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.

-0.9
Solubility 18.5 mg/ml ; 0.126 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.

-1.21
Solubility 8.95 mg/ml ; 0.0612 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

-0.99
Solubility 14.9 mg/ml ; 0.102 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

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.

-6.72 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

1.0
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

0.0 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)

1.58

Application In Synthesis of [ 14002-73-4 ]

* 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.

  • Upstream synthesis route of [ 14002-73-4 ]

[ 14002-73-4 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 4835-90-9 ]
  • [ 75-03-6 ]
  • [ 14002-73-4 ]
YieldReaction ConditionsOperation in experiment
68% With caesium carbonate In N,N-dimethyl-formamide at 50 - 70℃; A dry 500 mL round-bottomed flask equipped with a magnetic stirring bar, a reflux condenser, and a rubber septum was charged under an atmosphere of nitrogen with 7.09 g (60.0 mmol) of 3-hydroxy-2,2-dimethylpropanoic acid (hydroxypivalic acid, HPA) or 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid (bis-hydroxypivalic acid, BHPA) and 19.55 g (60.0 mmol) of dried and freshly powdered cesium carbonate (Cs2CO3). 150 mL of anhydrous dimethylformamide (DMF) was added followed by 0.7-1.0 equivalents (40.0 to 60.0 mmol) of an appropriately substituted alkyl halide. The reaction mixture was heated under an atmosphere of nitrogen for overnight to ca. 50-70° C. (oil bath) (depending on the boiling point of the halide). The reaction mixture was diluted with ethyl acetate, precipitates were filtered off, and the filtrate was carefully diluted with a one molar (1.0 M) of hydrochloric acid (HCl). The aqueous phase was extracted several times with ethyl acetate and the combined organic extracts were washed with a saturated aqueous solution of sodium hydrogen carbonate (NaHCO3). The organic solvents were removed under reduced pressure using a rotary evaporator and the residue was diluted in methyl tert-butyl ether (MTBE). The organic solution was washed five times with water (to remove residual DMF), then brine, dried over anhydrous magnesium sulfate (MgSO4), filtered and the residual solvents removed under reduced pressure using a rotary evaporator. Generally, the products were of sufficient purity to be used directly in the next step without further purification or, optionally, were purified by fractional distillation under reduced pressure or silica gel column chromatography using ethyl acetate/hexane mixtures as eluent. Following the general procedure for the synthesis of hydroxypivalic ester derivatives of Description 2, 4.73 g (40.0 mmol) of 3-hydroxy-2,2-dimethylpropanoic acid (hydroxypivalic acid, HPA) was reacted with 3.23 mL (6.24 g, 40.0 mmol) of iodoethane in 80 mL of DMF in the presence of 13.03 g (40.0 mmol) of Cs2CO3.
After work-up, 3.40 g (68percent yield) of the title compound (2) was obtained as a yellow liquid.
The material was of sufficient purity to be used in the next step without further purification. 1H NMR (400 MHz, CDCl3): δ=1.20 (s, 6H), 1.28 (t, J=7.2 Hz, 3H), 2.50-2.55 (br. m, 1H), 3.52-3.57 (br. m, 2H), 4.16 (q, J=7.2 Hz, 2H) ppm.
References: [1] Patent: US2009/69419, 2009, A1, . Location in patent: Page/Page column 43-44.
  • 2
  • [ 64-17-5 ]
  • [ 4835-90-9 ]
  • [ 14002-73-4 ]
References: [1] Bulletin de la Societe Chimique de France, 1904, vol. &lt;3&gt;31, p. 129.
[2] Journal of Organic Chemistry, 1973, vol. 38, p. 2346 - 2350.
[3] Journal of the American Chemical Society, 1962, vol. 84, p. 3307 - 3319.
  • 3
  • [ 600-00-0 ]
  • [ 50-00-0 ]
  • [ 14002-73-4 ]
References: [1] Justus Liebigs Annalen der Chemie, 1969, vol. 725, p. 106 - 115.
 

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