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Chemical Structure| 51105-90-9

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Methyl 1H-pyrazole-4-carboxylate

CAS No.: 51105-90-9

4.5 *For Research Use Only !

Cat. No.: A165507 Purity: 97%

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Product Details of [ 51105-90-9 ]

CAS No. :51105-90-9
Formula : C5H6N2O2
Linear Structure Formula :C3(CO2CH3)H3N2
M.W : 126.11
SMILES Code : O=C(C1=CNN=C1)OC
MDL No. :MFCD00297363
Boiling Point : No data available
InChI Key :VFTZKSMAJVLWOV-UHFFFAOYSA-N
Pubchem ID :9793760

Safety of [ 51105-90-9 ]

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

Calculated chemistry of [ 51105-90-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 5
Fraction Csp3 0.2
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 29.87
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.

0.82
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

0.07
Log Po/w (WLOGP)?

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

0.2
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.

-0.4
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

0.8
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.3

Water Solubility

Log S (ESOL):?

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

-0.95
Solubility 14.3 mg/ml ; 0.113 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.

-0.78
Solubility 21.0 mg/ml ; 0.167 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

-1.27
Solubility 6.77 mg/ml ; 0.0537 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

No
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.

-7.02 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)

1.18

Application In Synthesis [ 51105-90-9 ]

* 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 [ 51105-90-9 ]

[ 51105-90-9 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 37718-11-9 ]
  • [ 51105-90-9 ]
YieldReaction ConditionsOperation in experiment
79.6% With hydrogenchloride; In methanol; water; 3. Preparation of 4-carbomethoxypyrazole (5): To an ice cold saturated solution of HCl in methanol (500 ml), <strong>[37718-11-9]pyrazole-4-carboxylic acid</strong> (4) (19.2 g, 0.17 m) was added and the solution stirred at 0° C. for 3 hours and at ambient temperature overnight. The solvent was distilled off and the brown residue was dissolved in water. The aqueous solution was neutralized with NaHCO3 and the product was repeatedly extracted with ether (25*100 ml). The ether extract was dried over Mg SO4 and concentrated to give the methyl ester (5) as a pale yellow solid (13.59 g, 79.6percent).
With sulfuric acid; sodium methylate; In methanol; chloroform; PREPARATIVE EXAMPLE 6 Synthesis of methyl pyrazole-4-carboxylate <strong>[37718-11-9]4-Pyrazolecarboxylic acid</strong> (514 mg) was dissolved in methanol (10 ml) and sulfuric acid (0.25 ml), and the mixture was stirred at room temperature for 2 hours, followed by refluxing under heating for 4 hours. After cooling, a 28percent solution (0.95 ml) of sodium methylate in methanol was added to the reaction mixture for neutralization and the solvent was distilled away. Chloroform was added to the residue, and the residue was washed with water and brine and dried over anhydrous magnesium sulfate. The solvent was distilled away to give 433 mg of the title compound. 1 H-NMR(CDCl3 /ppm) delta3.92(3H, s), 8.08(2H, s), 8.26(1H, br s)
  • 3
  • [ 67-56-1 ]
  • [ 37718-11-9 ]
  • [ 51105-90-9 ]
YieldReaction ConditionsOperation in experiment
93.32% With sulfuric acid; at 0 - 80℃; for 16h; To the stirred solution of lH-pyrazole-4-carboxylic add 19-1 (20 g, 178.43 mmol) in methanol (100 niL) was added H2SO4 (17.50 g, 178.43 mmol, 9.51 rnL) at 0C and the reaction mixture was refluxed for 16 hours at 80C. Solvent was evaporated and the crude material was neutralized by saturated sodium bicarbonate solution. The aqueous layer was extracted with ethyl acetate and washed with brine. After separation, the organic layer was dried over sodium sulfate and evaporated to obtain methyl lH-pyrazole-4-earboxylate 19-2 (21 g, 166.52 mmol, 93.32% yield) as white solid. LC MS: ES+127.0.
78% With sulfuric acid; at 70℃; for 20h; 1 H-<strong>[37718-11-9]pyrazole-4-carboxylic acid</strong> (20 g, 178.4 mmol) and sulfuric acid (39.65 ml)in MeOH (200 ml) were heated at 70C for 20 h. The reactbn mixture was cooled to room temperature and concentrated in vacuo. Aqueous NaOH solution was added to adjust the pH to ~6. The aqueous layer was extracted with EtOAc (3 x 200 ml) and the combined organic extracts were dried (MgSQ;), filtered and evaporated in vacuo to afford the title compound (18.5 g , 78%) as a white solid. 1 H-NMR (CDCI3, 500 MHz): d[ppm]= 8.10 (s, 2H), 3.87 (s, 3H) HPLCMS (Method A): [m/z]: 126.85 [M+H]+
5 g With hydrogenchloride; at 10 - 35℃; A) methyl 1H-pyrazol-4-carboxylate A mixture of <strong>[37718-11-9]1H-pyrazol-4-carboxylic acid</strong> (4.00 g) and 4 M hydrogen chloride/methanol solution (150 mL) was stirred overnight at room temperature, and the solvent was evaporated under reduced pressure to give the title compound (5.0 g). 1H NMR (400 MHz, DMSO-d6) delta 3.72 (3H, s), 8.09 (2H, s), 11.62 (1H, s).
4.5 g With sulfuric acid; at 0℃;Reflux; To a mixture of lH-<strong>[37718-11-9]pyrazole-4-carboxylic acid</strong> (5.00 g, 44.6 mmol) in dry CH3OH (100 mL) was added drop-wise H2S04 (874 mg, 8.92 mmol) at 0C. The mixture was stirred at reflux overnight. A solution of NaOH (3.83 g, 95.7 mmol, 10 N) was added drop- wise to the reaction mixture. The mixture was poured into ice-water and diluted with ethyl acetate. The organic layer was washed with saturated aqueous lithium chloride solution and brine successively, dried over anhydrous Na2SC>4 and concentrated. The residue was purified by silica gel chromatography (petroleum ether : ethyl acetate = 10 : 1) to give methyl 1H- pyrazole-4-carboxylate (4.50 g) as a white solid. LC-MS (ESI) found: 127 [M+H]+.

  • 4
  • [ 51105-90-9 ]
  • [ 121138-01-0 ]
  • methyl 1-tetrahydrofuran-3-ylpyrazole-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
71.1% With caesium carbonate; In N,N-dimethyl-formamide; To a mixture of methyl 1H-pyrazole-4-carboxylate (800 mg, 6.34 mmol, 1 eq) and 3- iodotetrahydrofuran (1.51 g, 7.61 mmol, 1.2 eq) in DMF (8 mL) was added cesium carbonate (4.13 g, 12.7 mmol, 2 eq) at 20 C under nitrogen. The mixture was stirred at 20 C for 4 h. The residue was poured into ice-water (w/w = 1/1) (100 mL). The aqueous phase was extracted with EA (30 mLx3). The combined organic phase was washed with brine (30 mLx3), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography to give methyl 1-cyclopentylpyrazole-4-carboxylate as a white solid in 71.1% yield. LC-MS (ES+, m/z): 198.0 [(M+H)+].
 

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