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Chemical Structure| 204196-80-5 Chemical Structure| 204196-80-5

Structure of 204196-80-5

Chemical Structure| 204196-80-5

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Product Details of [ 204196-80-5 ]

CAS No. :204196-80-5
Formula : C8H6N4O2
M.W : 190.16
SMILES Code : OC(=O)C1=CC(=CC=C1)N1C=NN=N1
MDL No. :MFCD00574247
InChI Key :UNTMKIYQHROFCP-UHFFFAOYSA-N
Pubchem ID :750220

Safety of [ 204196-80-5 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H228
Precautionary Statements:P501-P270-P240-P210-P241-P264-P280-P370+P378-P301+P312+P330
Class:4.1
UN#:1325
Packing Group:

Computational Chemistry of [ 204196-80-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 11
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 46.11
TPSA ?

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

80.9 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.23
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

0.62
Log Po/w (WLOGP)?

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

0.36
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.

1.07
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

-0.14
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.63

Water Solubility

Log S (ESOL):?

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

-1.86
Solubility 2.63 mg/ml ; 0.0138 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.

-1.89
Solubility 2.43 mg/ml ; 0.0128 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

-1.56
Solubility 5.26 mg/ml ; 0.0277 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.

0.56

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)

1.76

Application In Synthesis of [ 204196-80-5 ]

* 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 [ 204196-80-5 ]

[ 204196-80-5 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 168618-33-5 ]
  • [ 204196-80-5 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; lithium hydroxide; sodium hydroxide; In water; Combine ethyl 3-(1H-tetrazol-1-yl)benzoate (4.93 g, 22.6 mmol) and tetrahydrofuran/water (100 mL/25 mL). Add lithium hydroxide (1.9 g, 45.2 mmol) and heat to reflux. After 2 hours, cool to ambient temperature and extract the reaction mixture five times with a 1 M aqueous sodium hydroxide solution. Combine the aqueous layers and extract with ethyl acetate. Acidify the aqueous layers with a 1 M aqueous hydrochloric acid solution (pH about 1) to give a solid. Collect the solid by filtration to give the title compound.
With hydrogenchloride; lithium hydroxide; sodium hydroxide; In water; Combine ethyl 3-(1H-tetrazol-1-yl)benzoate (4.93 g, 22.6 mmol) and tetrahydrofuran/water (100 mL/25 mL). Add lithium hydroxide (1.9 g, 45.2 mmol) and heat to reflux. After 2 hours, cool to ambient temperature and extract the reaction mixture five times with a 1M aqueous sodium hydroxide solution. Combine the aqueous layers and extract with ethyl acetate. Acidify the aqueous layers with a 1M aqueous hydrochloric acid solution (pH about 1) to give a solid. Collect the solid by filtration to give the title compound.
With hydrogenchloride; lithium hydroxide; sodium hydroxide; In water; Combine ethyl 3-(1H-tetrazol-1-yl)benzoate (4.93 g, 22.6 mmol) and tetrahydrofuran/water (100 mL/25 mL). Add lithium hydroxide (1.9 g, 45.2 mmol) and heat to reflux. After 2 hours, cool to ambient temperature and extract the reaction mixture five times with a 1 M aqueous sodium hydroxide solution. Combine the aqueous layers and extract with ethyl acetate. Acidify the aqueous layers with a 1 M aqueous hydrochloric acid solution (pH about 1) to give a solid. Collect the solid by filtration to give the title compound.
With hydrogenchloride; lithium hydroxide; sodium hydroxide; In water; Combine ethyl 3-(1H-tetrazol-1-yl)benzoate (4.93 g, 22.6 mmol) and tetrahydrofuran/water (100 mL/25 mL). Add lithium hydroxide (1.9 g, 45.2 mmol) and heat to reflux. After 2 hours, cool to ambient temperature and extract the reaction mixture five times with a 1 M aqueous sodium hydroxide solution. Combine the aqueous layers and extracts with ethyl acetate. Acidify the aqueous layers with a 1 M aqueous hydrochloric acid solution (pH about 1) to give a solid. Collect the solid by filtration to give the title compound.
With hydrogenchloride; lithium hydroxide; sodium hydroxide; In water; Combine ethyl 3-(1H-tetrazol-1-yl)benzoate (4.93 g, 22.6 mmol) and tetrahydrofuran/water (100 mL/25 mL). Add lithium hydroxide (1.9 g, 45.2 mmol) and heat to reflux. After 2 hours, cool to ambient temperature and extract the reaction mixture five times with a 1 M aqueous sodium hydroxide solution. Combine the aqueous layers and extract with ethyl acetate. Acidify the aqueous layers with a 1 M aqueous hydrochloric acid solution (pH about 1) to give a solid. Collect the solid by filtration to give the title compound.

  • 2
  • [ 204196-80-5 ]
  • [ 6148-64-7 ]
  • [ 335256-05-8 ]
YieldReaction ConditionsOperation in experiment
With MgCl2; triethylamine; In acetonitrile; Example M15 3-Oxo-3-(3-tetrazol-1-yl-phenyl)-propionic acid ethyl ester Prepared from <strong>[204196-80-5]3-tetrazol-1-yl-benzoic acid</strong> [CAS-No. 204196-80-5] by activation with ethyl chloroformate/Et3N and reaction with ethyl malonate potassium salt with Et3N and MgCl2 in CH3CN according to general procedure M (method a). Obtained as a light yellow solid (211 mg). MS (EI) 260 (M+).
With MgCl2; triethylamine; In acetonitrile; Example H15 3-Oxo-3-(3-tetrazol-1-yl-phenyl)-propionic Acid Ethyl Ester Prepared from <strong>[204196-80-5]3-tetrazol-1-yl-benzoic acid</strong> [CAS-No. 204196-80-5] by activation with ethyl chloroformate/Et3N and reaction with ethyl malonate potassium salt with Et3N and MgCl2 in CH3CN according to general procedure H (method a). Obtained as a light yellow solid (211 mg). MS (EI) 260 (M+).
  • 3
  • [ 204196-80-5 ]
  • (-)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine(R,R)-di-p-anisoyltartaric acid salt [ No CAS ]
  • [ 192940-77-5 ]
  • 1-(3-(1H-tetrazol-1-yl)benzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
71.1 Synthesis of 1-(3-(1H-tetrazol-1-yl)benzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine Prepare by the method of Example 56.1 using <strong>[204196-80-5]3-(1H-tetrazol-1-yl)benzoic acid</strong> and 3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine hydrochloric acid salt (prepared from (-)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine(R,R)-di-p-anisoyltartaric acid salt) to give the title compound.
  • 4
  • [ 204196-80-5 ]
  • [ 1133464-33-1 ]
  • 3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine hydrochloric acid salt [ No CAS ]
  • 1-(3-(1H-tetrazol-1-yl)benzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
74.1 Synthesis of 1-(3-(1H-tetrazol-1-yl)benzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine Prepare by the method of Example 59.1 using <strong>[204196-80-5]3-(1H-tetrazol-1-yl)benzoic acid</strong> and 3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine hydrochloric acid salt (prepared from (-)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid salt) to give the title compound.
  • 5
  • [ 204196-80-5 ]
  • [ 951895-34-4 ]
  • [ 1035231-35-6 ]
  • 6
  • [ 99-05-8 ]
  • [ 122-51-0 ]
  • [ 204196-80-5 ]
  • 7
  • [ 204196-80-5 ]
  • [ 1082752-89-3 ]
YieldReaction ConditionsOperation in experiment
With thionyl chloride; at 80℃; Thionyl chloride (477 mL, 6.58 mmol) and 3-(lH-tetrazol-l-yl)benzoic acid. (50 mg, 0.263 mmol) was heated to 80 C in a screw-cap vial. After a clear solution was observed, the residue solid on the wall was washed by gentle shaking. After 1.5 h, the reaction was cooled to room temperature. The reaction mixture was concentrated to dryness under reduced pressure. The resulting white solid was suspended in CH2Cl2 (1.5 mL) and treated with p-bromoaniline (90 mg, 0.526 mmol) and triethylamine (100 mL, 0.719 mmol). The reaction was stirred at room temperature for 14 h, mixed with silica gel and concentrated to dryness. Chromatography [silica, CH2Cl2:methanol (98:2 to 1 :3)] yielded an off-white solid (48 mg, 53%). Decomp point 203 C. 1H NMR (300 MHz, DMSO-d6) d 7.58 (d, J= 4.9, 2H), 7.79 (d, J= 4.9, 2H), 7.85 (6, J= 8.0, 1H), 8.10-8.18 (m, 2H), 8.47-8.51 (m, 1H), 10.22 (s, 1H), 10.62 (br, 1H, NH). 13C NMR (75 mHz, DMSO-d6) delta 120.18, 122.08, 123.92, 128.50, 130.11, 131.30, 142.25. ESI-MS Calculated for C14H10BrN5O 344.0141; found 344.0152.
With thionyl chloride; N,N-dimethyl-formamide; for 3.0h;Reflux; General procedure: To the solution of carboxylic acid (1eq.) in thionyl chloride were added one drop DMF. The mixture was heated to reflux temperature and stirred for 3 h. The solvent was removed and the crude material dissolved in DCM. To this solution were added the amine (1eq.) and triethylamine (1.5eq). The mixture was stirred for 3 h at room temperature under argon. Afterwards the DCM was removed. The crude material was dissolved in ethyl acetate and washed with water and brine. The resulting organic layer was dried over MgSO4, and the solvent was removed by evaporation. The obtained residue was purified by flash chromatography (CH2Cl2/MeOH).
  • 8
  • [ 204196-80-5 ]
  • [ 915910-44-0 ]
  • 9
  • [ 204196-80-5 ]
  • [ 484039-66-9 ]
  • 10
  • [ 204196-80-5 ]
  • (S)-2-amino-N-(1-cyanocyclopropyl)-3-(pyridin-3-yl)propanamide [ No CAS ]
  • C20H18N8O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 4.0h; General procedure: (S)-2-amino-N-(1-cyanocyclopropyl)-3-(pyridin-3-yl)propanamide (1 Eq.) acid (1 Eq.) and HATU (1.2 Eq.) were dissolved in DMF (0.145 M). DIPEA (4 Eq.) was added dropwise at room temperature and mixture stirred for 4H. The mixture was charged on a Si-CO3 cartridge (2 g) and eluted with MeOH. Volatiles were removed and crude purified by preparative Rp HPLC (MeCN/Water + 0.1% TFA).
  • 11
  • [ 204196-80-5 ]
  • N-(1H-indazol-5-yl)-3-(1H-tetrazol-1-yl)benzamide [ No CAS ]
 

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