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Chemical Structure| 3528-58-3

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1-Ethyl-1H-pyrazol-5-amine

CAS No.: 3528-58-3

4.5 *For Research Use Only !

Cat. No.: A158859 Purity: 97%

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Product Details of [ 3528-58-3 ]

CAS No. :3528-58-3
Formula : C5H9N3
M.W : 111.15
SMILES Code : CCN1N=CC=C1N
MDL No. :MFCD00010849
InChI Key :FSJOLBAFVKSQQJ-UHFFFAOYSA-N
Pubchem ID :337310

Safety of [ 3528-58-3 ]

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

Calculated chemistry of [ 3528-58-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 5
Fraction Csp3 0.4
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 32.7
TPSA ?

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

43.84 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.05
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

0.19
Log Po/w (WLOGP)?

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

0.49
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.

0.14
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

-0.05
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.37

Water Solubility

Log S (ESOL):?

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

-1.05
Solubility 10.0 mg/ml ; 0.0901 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.

-0.67
Solubility 23.8 mg/ml ; 0.214 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

-0.78
Solubility 18.4 mg/ml ; 0.166 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.

-6.84 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)

1.4

Application In Synthesis [ 3528-58-3 ]

* 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 [ 3528-58-3 ]

[ 3528-58-3 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 3528-58-3 ]
  • [ 3044-06-2 ]
  • [ 41095-06-1 ]
YieldReaction ConditionsOperation in experiment
at 150℃; for 5h;Product distribution / selectivity; Alternative preparation of ethyl 4-chloro-1-ethyl-6-methyl-1H-pyrazolo[3,4-blpvridine-5- carboxylate: A mixture of 5-amino-1-ethylpyrazole (1.614g, 14.5mmol) and diethyl 2-(1- ethoxyethylidene)malonate [e.g. see J. Am. Chem. Soc, 1931, 53, 1836] (3.68g) is heated at 150 0C under Dean Stark conditions for 5 hours. Phosphorous oxychloride (25ml) is carefully added to the mixture and the resulting solution is heated at 130 0C under reflux for 18 hours. The mixture is concentrated in vacuo and the residual oil is carefully added, with cooling, to water (100ml). The resulting mixture is extracted with dichloromethane (3 x 100ml) and the combined organic extracts are dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil is purified by Biotage chromatography (silica; 9Og) eluting with 5% ethyl acetate in petroleum ether. Fractions containing the desired product are combined and concentrated in vacuo to give ethyl 4-chloro-1 -ethyl-6-methyl-1 /-/-pyrazolo[3,4-]pyridine-5-carboxylate..
  • 2
  • [ 3528-58-3 ]
  • [ 3044-06-2 ]
  • [ 41095-07-2 ]
YieldReaction ConditionsOperation in experiment
57.17% A mixture of l-ethyl-lH-pyrazol-5-amine (16 gm, 0.144 moles) (example 2) and 2-(l-ethoxy-ethylidene)-malonic acid diethyl ester (29 gm, 0.12 moles) (example 3) was stirred at 1200C for about 2 hrs. When the reaction was complete on TLC, crude reaction mixture was concentrated in vacuo to remove ethanol, which was formed as byproduct. Crude residue was taken in phosphorous oxychloride (50 ml) and heated at 115 C for about 12-13 hrs. The reaction mixture was poured into ice-cooled water with continuous stirring. Solid which precipitated out was filtered and dried under vacuum to afford title compound as creamy white solid.Yield: 12 gm (57.17%) m/z: (M++l) 268.28
Intermediate 11: Ethyl 4-chloro-1-ethyl-6-methyl-lH-pyrazolo [3, 4-b] pyridine-5- carboxylate; A mixture of 5-amino-1-ethylpyrazole (1.614g, 14. 5mmol) and diethyl 2- (1- ethoxyethylidene) malonate (3.68g, 16. 0mmol, as described by P. P. T. Sah, J. Amer. Chem. Soc., 1931,53, 1836) was heated at 150 C under Dean Stark conditions for 5 hours. Phosphorous oxychloride (25ml) was carefully added to the mixture and the resulting solution was heated at 130 C under reflux for 18 hours. The mixture was concentrated in vacuo, then the residual oil was carefully added, with cooling, to water (100ml). The resulting mixture was extracted with DCM (3xlOOml) and the combined organic extracts were dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil was purified by Biotage chromatography (silica, 90g) eluting with ethyl acetate-petrol (1: 19). Fractions containing the desired product were combined and concentrated in vacuo to afford Intermediate 58 (1. 15g). LCMS showed MH+ = 268 ; TpBT = 3. 18min
A mixture of 5-amino-1-ethylpyrazole (1.614g, [14.] [5MMOL)] and diethyl [2- (1-] ethoxyethylidene) malonate (3.68g, [16.] [0MMOL,] as described by P. P. T. Sah, [J AMER.] Chem. Soc., 1931,53, 1836) was heated at [150 C] under Dean Stark conditions for 5 hours. Phosphorous oxychloride [(25ML)] was carefully added to the mixture and the resulting solution was heated at [130 C] under reflux for 18 hours. The mixture was concentrated in vacuo, then the residual oil was carefully added, with cooling, to water [(100ML).] The resulting mixture was extracted with DCM [(3XLOOML)] and the combined organic extracts were dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil was purified by Biotage chromatography (silica, 90g) eluting with ethyl acetate-petrol (1: 19). Fractions containing the desired product were combined and concentrated in vacuo to afford Intermediate 51 (1.15g). LCMS showed MH+ = 268; TRET = 3. [18MIN.]
A mixture of 5-amino-1-ethylpyrazole (1.614 g, 14.5 mmol) and <strong>[3044-06-2]diethyl 2-(1-ethoxyethylidene)malonate</strong> [J. Am. Chem. Soc., 1931, 53, 1836] (3.68 g) was heated at 150 C. under Dean Stark conditions for 5 hours. Phosphorous oxychloride (25 ml) was carefully added to the mixture and the resulting solution was heated at 130 C. under reflux for 18 hours. The mixture was concentrated in vacuo and the residual oil was carefully added, with cooling, to water (100 ml). The resulting mixture was extracted with dichloromethane (3*100 ml) and the combined organic extracts were dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil was purified by Biotage chromatography (silica; 90 g) eluding with 5% ethyl acetate in petroleum ether. Fractions containing the desired product were combined and concentrated in vacuo to give Intermediate 17 (1.15 g). LCMS showed MH+=268; TRET=3.18 min.
Intermediate 17: Ethyl 4-chloro-1-ethyl-6-methyl-1H-pyrazolo[3,4-Jb]pyridine-5- carboxylate EPO <DP n="145"/>A mixture of 5-amino-i-ethylpyrazole (1.614g, 14.5mmol) and diethyl 2-(1- ethoxyethylidene)malonate [J. Am. Chem. Soc, 1931, 53, 1836 (3.68g) was heated at 150 0C under Dean Stark conditions for 5 hours. Phosphorous oxychloride (25ml) was carefully added to the mixture and the resulting solution was heated at 130 0C under reflux for 18 hours. The mixture was concentrated in vacuo and the residual oil was carefully added, with cooling, to water (100ml). The resulting mixture was extracted with dichloromethane (3 x 100ml) and the combined organic extracts were dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil was purified by Biotage chromatography (silica; 9Og) eluting with 5% ethyl acetate in petroleum ether. Fractions containing the desired product were combined and concentrated in vacuo to give Intermediate 17 (1.15q). LCMS showed MH+ = 268; TREtau = 3.18min.

 

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