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Chemical Structure| 3699-66-9 Chemical Structure| 3699-66-9

Structure of 3699-66-9

Chemical Structure| 3699-66-9

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Synonyms: Triethyl 2-phosphonopropionate

4.5 *For Research Use Only !

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Product Details of [ 3699-66-9 ]

CAS No. :3699-66-9
Formula : C9H19O5P
M.W : 238.22
SMILES Code : CCOC(=O)C(C)P(=O)(OCC)OCC
Synonyms :
Triethyl 2-phosphonopropionate
MDL No. :MFCD00009159
InChI Key :BVSRWCMAJISCTD-UHFFFAOYSA-N
Pubchem ID :107155

Safety of [ 3699-66-9 ]

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

Computational Chemistry of [ 3699-66-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 0
Fraction Csp3 0.89
Num. rotatable bonds 8
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 57.5
TPSA ?

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

71.64 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.65
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

0.9
Log Po/w (WLOGP)?

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

2.2
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.

0.83
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

0.75
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.47

Water Solubility

Log S (ESOL):?

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

-1.36
Solubility 10.5 mg/ml ; 0.0441 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.

-1.99
Solubility 2.44 mg/ml ; 0.0102 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

-1.89
Solubility 3.09 mg/ml ; 0.013 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.

-7.11 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<2.0
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)

4.09

Application In Synthesis of [ 3699-66-9 ]

* 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 [ 3699-66-9 ]

[ 3699-66-9 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 3699-66-9 ]
  • [ 4395-92-0 ]
  • (Z)-4-(4-Isopropyl-phenyl)-2-methyl-but-2-enoic acid ethyl ester [ No CAS ]
  • 2
  • [ 3699-66-9 ]
  • [ 4395-92-0 ]
  • (E)-4-(4-Isopropyl-phenyl)-2-methyl-but-3-enoic acid ethyl ester [ No CAS ]
  • 3
  • [ 24686-78-0 ]
  • [ 3699-66-9 ]
  • [ 168888-64-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In tetrahydrofuran; mineral oil; (a) A solution of triethyl 2-phosphonopropionate (50.0 g) in dry tetrahydrofuran (75 ml) was added dropwise to a stirred suspension of sodium hydride (60percent in mineral oil, 8.0 g) in dry tetrahydrofuran (275 ml) under nitrogen and stirred at 20° C. for 10 minutes until a clear solution was formed. <strong>[24686-78-0]1-Benzoyl-4-piperidone</strong> (34.5 g) in dry tetrahydrofuran (75 ml) was added dropwise to the clear solution and the reaction mixture heated under reflux for 16 hours. After quenching the reaction mixture with 5M hydrochloric acid (20 ml), the resulting solid was removed by filtration. Excess ether was added to the filtrate, the aqueous layer separated off and the ethereal layer washed (water), dried, filtered and concentrated to give ethyl 2-(1-benzoyl-4-piperidylidene)propionate as an oil.
  • 4
  • [ 3699-66-9 ]
  • [ 109179-31-9 ]
  • C13H15BrO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
<Step 2>NaH (60percent assay, 193 mg, 4.82 mmol) was suspended in DMF (10 mL) and then cooled to 0° C. Triethyl 2-phosphonopropionate (1.05 mg, 4.82 mmol) in DMF (10 mL) was added dropwise in a slow manner to the solution and then stirred for 15 minutes. Then, the aldehyde obtained from Step 1 (640 mg, 3.22 mmol) in DMF (3 mL) was added thereto in a slow manner and then stirred for 18 hours while gradually heating it from 0° C. to room temperature. EtOAc was then added to the reaction solution, washed with water and saturated saline and then dried over anhydrous MgSO4. The solvent was eliminated in vacuo to obtain a residue. The resulting residue was then dissolved in THF (10 mL) and MeOH (4 mL), 2 N NaOH (8 mL, 8 mmol) was added thereto and then stirred at room temperature for 8 hours. The solvent was then eliminated in vacuo, 2 N HCl was added to acidify the solution and then the crystals precipitated were filtrated to obtain white crystals of the objective carboxylic acid (600 mg, 93percent).MS: 256
  • 5
  • [ 22929-52-8 ]
  • [ 3699-66-9 ]
  • ethyl 2-(dihydrofuran-3(2H)-ylidene)propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.3 g Description 34Ethyl 2-(dihydrofuran-3(211)-ylidene)propanoate (D34)To a solution of sodium hydride (1.394 g) in THF (60 mL) at 0 °C was added dropwise ethyl 2-(diethoxyphosphoryl)propanoate (8.29 g) under N2. The mixture was stirred at 0°C for 30 mm until the mixture became clear, then <strong>[22929-52-8]dihydrofuran-3(2H)-one</strong> (1.5 g) was added. The mixture was stirred at RT for 2 hours and then quenched by water (100 mL). The mixture was extracted with EtOAc(3 x50 mL). The combined organic layer was washed with brine (100 mL), dried and evaporated under vacuum. The crude product was purified by column chromatography (silica gel, petroleum ether/EtOAc = 30:1) to afford the title compound (1.3 g). MS (ESI): C9H1403 requires 170; found 171 [M+H].
  • 6
  • [ 3699-66-9 ]
  • [ 5779-93-1 ]
  • ethyl 3-(2,3-dimethylphenyl)-2-methylacrylate [ No CAS ]
  • ethyl 3-(2,3-dimethylphenyl)-2-methylacrylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium ethanolate; In ethanol; pentane; for 0.75h;Reflux; Cooling; Ethyl 2-(diethoxyphosphoryl)propanoate (80.0 g, 335 mmol, 1.5 eq) was added to a stirred solution of <strong>[5779-93-1]2,3-dimethylbenzaldehyde</strong> (30.0 g, 224 mmol, 1.0 eq) in pentane (300 mL) at room temperature. A solution of NaOEt (21percent w/w in EtOH, 109 mL, 293 mmol, 1.3 eq) was subsequently added dropwise under stirring, while cooling the reaction mixture with a water bath. Once the addition was completed, the resulting mixture was stirred at reflux for 45 minutes. The reaction mixture was then cooled to 0° C. and quenched by addition of aqueous NaOH (1 N , 300 mL). The organic layer was separated and washed again with NaOH (1 N, 300 mL). The combined aqueous layers were extracted with Et2O (3 x), washed with sat. aqueous NaHCO3, brine (twice), dried over MgSO4, filtered and concentrated in vacuo to afford an orange crude oil. Bulb-to bulb distillation (0.15 mbar, oven temp. 150-155° C.) afforded the product as a colorless oil (46.5 g, 213 mmol, 95percent yield; 94:6 mixture of E-Z isomers). 1H-NMR (major diastereoisomer):7.79 (s, 1H), 7.13-7.06 (m, 2H), 7.01 (m, J=3.00, m), 4.28 (q, J=7.13, 2H), 2.29 (s, 3H), 2.17 (s, 3H), 1.90 (d, J=1.40, 3H), 1.35 (t, J=7.13, 3H).
 

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