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Chemical Structure| 4949-44-4 Chemical Structure| 4949-44-4

Structure of Ethyl 3-oxopentanoate
CAS No.: 4949-44-4

Chemical Structure| 4949-44-4

Ethyl 3-oxopentanoate

CAS No.: 4949-44-4

Synonyms: Ethyl Propionylacetate

4.5 *For Research Use Only !

Cat. No.: A110114 Purity: 95%

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Product Details of [ 4949-44-4 ]

CAS No. :4949-44-4
Formula : C7H12O3
M.W : 144.17
SMILES Code : CCC(CC(OCC)=O)=O
Synonyms :
Ethyl Propionylacetate
MDL No. :MFCD00009317
InChI Key :UDRCONFHWYGWFI-UHFFFAOYSA-N
Pubchem ID :78656

Safety of [ 4949-44-4 ]

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

Computational Chemistry of [ 4949-44-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 0.71
Num. rotatable bonds 5
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 37.25
TPSA ?

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

43.37 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.9
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

0.72
Log Po/w (WLOGP)?

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

0.92
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.

0.64
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

1.13
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.06

Water Solubility

Log S (ESOL):?

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

-0.86
Solubility 20.0 mg/ml ; 0.139 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 8.91 mg/ml ; 0.0618 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

-1.48
Solubility 4.74 mg/ml ; 0.0329 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.

-6.67 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

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)

1.61

Application In Synthesis of [ 4949-44-4 ]

* 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.

  • Downstream synthetic route of [ 4949-44-4 ]

[ 4949-44-4 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 4949-44-4 ]
  • [ 101349-12-6 ]
  • [ 57816-80-5 ]
  • 2
  • [ 5754-35-8 ]
  • [ 4949-44-4 ]
  • [ 135833-70-4 ]
  • 3
  • [ 1446332-69-9 ]
  • [ 4949-44-4 ]
  • [ 1446333-28-3 ]
YieldReaction ConditionsOperation in experiment
95% With piperidine; acetic acid; In acetonitrile; at 80.0℃; for 4.0h; Step A: A mixture of tert-butyl 4-(4-formyl-3-hydroxyphenyl)piperazine-l- carboxylate (3.0 g, 9.8 mmol, prepared in Example 1, Part 2), ethyl 3-oxopentanoate (1.62 mL, 11.3 mmol), AcOH (650 mu, 12 mmol), piperidine (1.1 mL, 11.3 mmol), and CH3CN (24 mL) were heated at 80 C for 4 h. The reaction mixture was partitioned between CH2CI2 and H2O. The organic layer was dried over MgS04, filtered, and concentrated under vacuum. The residue was purified by silica gel column chromatography (10%> EtOAc in CH2CI2), followed by ether trituration, yielding tert-butyl 4-(2-oxo-3-propionyl-2H-chromen-7-yl)piperazine-l-carboxylate (3.6 g, 95%) as a yellow solid. 1H NMR (500 MHz, CDC13): delta 8.49 (1H, s), 7.50 (1H, d, J= 8.5 Hz), 6.83 (1H, dd, J= 8.5 Hz, 2.5 Hz), 6.67 (1H, d, J= 2 Hz), 3.63 (4H, m), 3.47 (4H, m), 3.16 (2H, q, J= 7 Hz), 1.52 (9H, s), 1.19 (3H, t, J= 7 Hz).
95% With piperidine; acetic acid; In acetonitrile; at 80.0℃; for 4.0h; Step A: A mixture of <strong>[1446332-69-9]tert-butyl 4-(4-formyl-3-hydroxyphenyl)piperazine-1-carboxylate</strong> (3.0 g, 9.8 mmol, prepared in Example 1, Part 2), ethyl 3-oxopentanoate (1.62 mL, 11.3 mmol), AcOH (650 muL, 12 mmol), piperidine (1.1 mL, 11.3 mmol), and CH3CN (24 mL) were heated at 80 C. for 4 h. The reaction mixture was partitioned between CH2Cl2 and H2O. The organic layer was dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by silica gel column chromatography (10% EtOAc in CH2Cl2), followed by ether trituration, yielding tert-butyl 4-(2-oxo-3-propionyl-2H-chromen-7-yl)piperazine-1-carboxylate (3.6 g, 95%) as a yellow solid. 1H NMR (500 MHz, CDCl3): delta 8.49 (1H, s), 7.50 (1H, d, J=8.5 Hz), 6.83 (1H, dd, J=8.5 Hz, 2.5 Hz), 6.67 (1H, d, J=2 Hz), 3.63 (4H, m), 3.47 (4H, m), 3.16 (2H, q, J=7 Hz), 1.52 (9H, s), 1.19 (3H, t, J=7 Hz).
  • 4
  • [ 76593-36-7 ]
  • [ 4949-44-4 ]
  • 7-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidin-1-yl)-2-ethyl-8,9-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one [ No CAS ]
  • 5
  • [ 76593-36-7 ]
  • [ 4949-44-4 ]
  • 7-chloro-2-ethyl-8,9-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% With polyphosphoric acid; at 120℃; for 2.0h; To a solution of 6-choro-3-amino-4,5-dimethylpyridazine (550 mg) in polyphosphoric acid (4 mL) was added ethyl 3-oxopentanoate {913 pL). The mixture was heated to 85 “C for 1 hour, then 120 C for 1 hour. While hot, the mixture was slowly transferred to a stirred solution of saturated aqueous NaHCC {~150 mL) and chloroform/IPA (4:1) (50 mL). Upon complete addition, the mixture was stirred for 10 minutes then the organic layer was isolated. The aqueous layers was further extracted with chloroform/IPA (4:1) (x3) and the organic layers were pooled, dried over MgS04, filtered, and concentrated under vacuum. Upon cooling, a solid precipitate was observed. Hexanes was added, the suspenion was sonicated, the solid was collected by vacuum filtration, and washed with hexanes to provide the title compound (469 mg, 57% yield) >95% dean by LCMS. NMR (400 MHz, CDC ) d 6.50 (s, 1H), 2.70 (q, J 7.6 Hz, 2H), 2.61 (s,3H), 2.48 (s, 3H), 1.30 (†., J = 7.6 Hz, 3H). ES-MS [M+l]+: 238.
57% With polyphosphoric acid; at 120℃; for 2.0h; To a solution of 6-choro-3-amino-4,5-dimethylpyridazine (550 mg) in polyphosphoric acid (4 mL) was added ethyl 3-oxopentanoate {913 pL). The mixture was heated to 85 “C for 1 hour, then 120 C for 1 hour. While hot, the mixture was slowly transferred to a stirred solution of saturated aqueous NaHCC {~150 mL) and chloroform/IPA (4:1) (50 mL). Upon complete addition, the mixture was stirred for 10 minutes then the organic layer was isolated. The aqueous layers was further extracted with chloroform/IPA (4:1) (x3) and the organic layers were pooled, dried over MgS04, filtered, and concentrated under vacuum. Upon cooling, a solid precipitate was observed. Hexanes was added, the suspenion was sonicated, the solid was collected by vacuum filtration, and washed with hexanes to provide the title compound (469 mg, 57% yield) >95% dean by LCMS. NMR (400 MHz, CDC ) d 6.50 (s, 1H), 2.70 (q, J 7.6 Hz, 2H), 2.61 (s,3H), 2.48 (s, 3H), 1.30 (†., J = 7.6 Hz, 3H). ES-MS [M+l]+: 238.
57% With polyphosphoric acid; at 120℃; for 2.0h; To a solution of 6-choro-3-amino-4,5-dimethylpyridazine (550 mg) in polyphosphoric acid (4 mL) was added ethyl 3-oxopentanoate {913 pL). The mixture was heated to 85 “C for 1 hour, then 120 C for 1 hour. While hot, the mixture was slowly transferred to a stirred solution of saturated aqueous NaHCC {~150 mL) and chloroform/IPA (4:1) (50 mL). Upon complete addition, the mixture was stirred for 10 minutes then the organic layer was isolated. The aqueous layers was further extracted with chloroform/IPA (4:1) (x3) and the organic layers were pooled, dried over MgS04, filtered, and concentrated under vacuum. Upon cooling, a solid precipitate was observed. Hexanes was added, the suspenion was sonicated, the solid was collected by vacuum filtration, and washed with hexanes to provide the title compound (469 mg, 57% yield) >95% dean by LCMS. NMR (400 MHz, CDC ) d 6.50 (s, 1H), 2.70 (q, J 7.6 Hz, 2H), 2.61 (s,3H), 2.48 (s, 3H), 1.30 (†., J = 7.6 Hz, 3H). ES-MS [M+l]+: 238.
 

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