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Chemical Structure| 73981-23-4 Chemical Structure| 73981-23-4
Chemical Structure| 73981-23-4

Ethyl 3-ethyl-1H-pyrazole-4-carboxylate

CAS No.: 73981-23-4

4.5 *For Research Use Only !

Cat. No.: A448116 Purity: 97%

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Product Details of [ 73981-23-4 ]

CAS No. :73981-23-4
Formula : C8H12N2O2
M.W : 168.19
SMILES Code : CCOC(=O)C1=CNN=C1CC
MDL No. :MFCD07367317
InChI Key :WHXXMZCNOHVIDX-UHFFFAOYSA-N
Pubchem ID :22831675

Safety of [ 73981-23-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P264-P270-P301+P312-P330

Calculated chemistry of [ 73981-23-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 5
Fraction Csp3 0.5
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 44.45
TPSA ?

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

54.98 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.27
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

1.27
Log Po/w (WLOGP)?

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

1.15
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.

0.67
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

1.86
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.24

Water Solubility

Log S (ESOL):?

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

-1.73
Solubility 3.15 mg/ml ; 0.0187 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.

-2.02
Solubility 1.59 mg/ml ; 0.00947 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

-2.5
Solubility 0.529 mg/ml ; 0.00315 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.

-6.42 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)

1.97

Application In Synthesis of [ 73981-23-4 ]

* 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 [ 73981-23-4 ]

[ 73981-23-4 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 73981-23-4 ]
  • [ 824-94-2 ]
  • [ 1105039-78-8 ]
  • [ 1105039-79-9 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In acetone; at 60.0℃; Ethyl 5-ethyl-l-(4-methoxybenzyl)-lH-pyrazole-4-carboxylate and ethyl 3-betathyl-l-(4- methoxybenzyl)- 1 H-pyrazole-4-carboxylateAccording to Scheme 9 Step 3: A suspension of ethyl 3-ethyl-lH-pyrazole-4- carboxylate (5.95 mmol, 1.0 g), l-(chloromethyl)-4-methoxybenzene (6.54 mmol, 0.89 mL) and K2CO3 (17.8 mmol, 2.46 g) in acetone (20 mL) was heated at 600C overnight. After evaporation of the solvent, water was added and the aqueous phase was extracted with DCM. The organic phase was dried over Na2SOzI, was filtered and was concentrated under reduced pressure. The crude product was purified by flash chromatography over silica gel using cyclohexane/AcOEt (95:5) as eluent to afford a mixture of ethyl 5-ethyl-l-(4-methoxybenzyl)-lH-pyrazole-4-carboxylate and of ethyl 3-ethyl-l-(4-methoxybenzyl)-lH-pyrazole-4-carboxylate (2.77 mmol, 800 mg, 47%) as a yellow oil.LC (Zorbax SB-Ci8, 3.5mum, 4.6x30mm Column): RT = 2.58 min.
With potassium carbonate; In acetone; at 60.0℃; According to Scheme 9 Step 3: A suspension of <strong>[73981-23-4]ethyl 3-ethyl-1H-pyrazole-4-carboxylate</strong> (5.95 mmol, 1.0 g), 1-(chloromethyl)-4-methoxybenzene (6.54 mmol, 0.89 mL) and K2CO3 (17.8 mmol, 2.46 g) in acetone (20 mL) was heated at 60 C. overnight. After evaporation of the solvent, water was added and the aqueous phase was extracted with DCM. The organic phase was dried over Na2SO4, was filtered and was concentrated under reduced pressure. The crude product was purified by flash chromatography over silica gel using cyclohexane/AcOEt (95:5) as eluent to afford a mixture of ethyl 5-ethyl-1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylate and of ethyl 3-ethyl-1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylate (2.77 mmol, 800 mg, 47%) as a yellow oil.LC (Zorbax SB-C18, 3.5 mum, 4.6×30 mm Column): RT=2.58 min.
  • 2
  • [ 89193-23-7 ]
  • [ 73981-23-4 ]
YieldReaction ConditionsOperation in experiment
43% With hydrazine; In ethanol; at 20.0℃; for 1h; Ethyl 3-ethyl-lH-pyrazole-4-carboxylateAccording to Scheme 9 Step 2: A solution of ()-ethyl 2-((dimethylamino)methylene)- 3-oxopentanoate (13.9 mmol, 2.76 g) and hydrazine (13.9 mmol, 0.44 mL) in EtOH (50 <n="64"/>niL) was stirred for 1 hour at room temperature. After evaporation of the solvent, the resulting crude product was purified by flash chromatography over silica gel using cyclohexane/AcOEt (80:20) as eluent to yield after evaporation ethyl 3-ethyl-lH- pyrazole-4-carboxylate (6.00 mol, 1.01 g, 43%) as a yellow oil. LC (Zorbax SB-Ci8, 3.5mum, 4.6x50mm Column): RT = 1.53 min; MS m/z ES+= 169.
43% With hydrazine; In ethanol; at 20.0℃; for 1h; According to Scheme 9 Step 2: A solution of (E)-ethyl 2-((dimethylamino)methylene)-3-oxopentanoate (13.9 mmol, 2.76 g) and hydrazine (13.9 mmol, 0.44 mL) in EtOH (50 mL) was stirred for 1 hour at room temperature. After evaporation of the solvent, the resulting crude product was purified by flash chromatography over silica gel using cyclohexane/AcOEt (80:20) as eluent to yield after evaporation ethyl 3-ethyl-1H-pyrazole-4-carboxylate (6.00 mol, 1.01 g, 43%) as a yellow oil.LC (Zorbax SB-C18, 3.5 mum, 4.6×50 mm Column): RT=1.53 min; MS m/z ES+=169.
YieldReaction ConditionsOperation in experiment
General procedure: [105] 3-Methyl-1H-pyrazole-4-carboxylic acid ethyl ester was obtained by the procedure of WO2009/137338. N,N-dimethyl-formamide dimethyl acetal and ethyl acetoacetate were refluxed for 1 h followed by stirring with hydrazine hydrate in ethanol at 80C for 2 h.
 

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