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Chemical Structure| 1128-56-9 Chemical Structure| 1128-56-9

Structure of 1128-56-9

Chemical Structure| 1128-56-9

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Product Details of [ 1128-56-9 ]

CAS No. :1128-56-9
Formula : C9H9N3
M.W : 159.19
SMILES Code : NC1=NN(C2=CC=CC=C2)C=C1
MDL No. :MFCD00100520
InChI Key :BQQFSUKXGGGGLV-UHFFFAOYSA-N
Pubchem ID :594320

Safety of [ 1128-56-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H319
Precautionary Statements:P305+P351+P338

Computational Chemistry of [ 1128-56-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 11
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 47.97
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.

1.54
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

1.54
Log Po/w (WLOGP)?

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

1.46
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.

1.52
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

0.82
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.38

Water Solubility

Log S (ESOL):?

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

-2.41
Solubility 0.62 mg/ml ; 0.00389 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.07
Solubility 1.36 mg/ml ; 0.00851 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

-2.56
Solubility 0.444 mg/ml ; 0.00279 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

Yes
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.

-6.18 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)

1.53

Application In Synthesis of [ 1128-56-9 ]

* 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 [ 1128-56-9 ]

[ 1128-56-9 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 1128-56-9 ]
  • [ 108-24-7 ]
  • [ 2753-56-2 ]
  • 2
  • [ 3314-35-0 ]
  • [ 1128-56-9 ]
YieldReaction ConditionsOperation in experiment
80% copper(l) chloride; In ethanol; EXAMPLE 2 Using the same apparatus as in Example 1 and following the same modalities, 5 g (0.031 mole) of 1-phenyl-3-amino-2-pyrazoline were suspended in 25 ml of ethanol with the addition of 0.1 g (0.001 mole) of CuCl and of 0.064 g (0.001 mole) of metallic Cu, under an oxygen head, at a temperature of 30 C. After about 2 hours, the oxidation was completed and the whole solid was dissolved. The catalyst was filtered and, after removal of the solvent under vacuum, 1-phenyl-3-aminopyrazole (I) was hot extracted with diluted HCl from which, after clarification with animal charcoal, 4 g of product (I) precipitated in the form of whitish needles by neutralization with aqueous NaOH. The melting point of the product was 89-90 C.; the yield was about 80% of the theoretical value.
41% With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In 1,4-dioxane; at 20℃; for 1h; To a solution of 1-phenyl-3-amino-pyrazoline(7.4 g, 46 mmol) in dioxane (200 mL) was added 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (11.54 g, 50 mmol). After addition, the reaction was stirred at RT for 1 hour, then the resulting dark solution was filtered through a pad of Celite. The filtrate was acidified with 1N aqueous HCl (100 mL) and extracted with CH2Cl2 (50 mL). The organic layer was extracted with 1N aqueous HCl (50 mL). The combined aqueous layers were washed with CH2Cl2 (2×50 mL), then adjusted to pH12 with NaOH, followed by extraction with CH2Cl2 (3×100 mL). The combined CH2Cl2 extracts were washed with saturated NaCl (100 mL), dried (MgSO4), and concentrated under reduced pressure to give the title compound, 1-phenyl-3-amino-pyrazole as light orange solid (3.0 g, 41% yield). LC/MS (method A): retention time=1.43 min, (M+H)+=160.
copper(l) chloride; In acetonitrile; EXAMPLE 4 Example 1 was repeated using the following amounts of reagents: 5 g (0.031 mole) of 1-phenyl-3-amino-2-pyrazoline were dissolved in 25 ml of acetonitrile under addition of 0.2 g (0.00201 mole) of CuCl, under an oxygen head. Oxidation lasted about 3 hours. 2.5 g of 1-phenyl-3-aminopyrazole were obtained.
copper(l) chloride; In acetic acid; EXAMPLE 5 Using the same apparatus as in Example 1 and following the same modalites, 5 g (0.031 mole) of 1-phenyl-3-amino-2-pyrazoline were dissolved in 15 ml of acetic acid with addition of 0.2 g (0.00201 mole) of CuCl, under an oxygen head. Oxidation was completed after about 5 hours. Acetic acid was neutralized with sodium bicarbonate, it was filtered and the precipitate was extracted with ether. By evaporating the ethereal solution, 1.5 g of 1-phenyl-3-aminopyrazole were obtained.
12.2 g To a solution of 1-phenyl-4,5-dihydro-1H-pyrazol-3-ylamine (50.0 g) in N,N-dimethylformamide (150 ml) and 1,4-dioxane (500 ml) was added 3,4,5,6-tetrachloro-1,4-benzoquinone (84.0 g) under ice-cooling over 20 minutes, and the mixture was stirred at room temperature for 4.5 hours. To the reaction mixture was added a 2M aqueous solution of sodium hydroxide (400 ml) under ice-cooling over 25 minutes, and the mixture was stirred at room temperature for 1 hour. The mixture was filtered through Celite to remove the insoluble substance, and eluted with ethyl acetate (250 ml*3), and then the filtrate was extracted with ethyl acetate (300 ml). The resulting organic layer was sequentially washed with water (300 ml) and a saturated aqueous solution of sodium chloride (300 ml). The separated aqueous layer was extracted twice with ethyl acetate (300 ml). To the combined organic layer were added anhydrous sodium sulfate (50 g) and silica gel (50 g), and the mixture was stirred at room temperature for 1 hour. This mixture was filtered with silica gel (100 g) on Celite, and subjected to elution with ethyl acetate (250 ml*3). The filtrate was concentrated, and diisopropyl ether (500 ml) was added to the resulting residue, and the mixture was stirred at room temperature. The insoluble substance was collected by filtration, washed twice with diisopropyl ether (100 ml), and dried under reduced pressure to give the titled compound (12.2 g). 1H-NMR (CDCl3) delta: 3.81 (br s, 2H), 5.85 (d, 1H, J=2.4 Hz), 7.16-7.19 (m, 1H), 7.38-7.40 (m, 2H), 7.55-7.57 (m, 2H), 7.69 (d, 1H, J=2.4 Hz).

  • 3
  • 1-phenyl-3-phenylazo-1<i>H</i>-pyrazole [ No CAS ]
  • [ 1128-56-9 ]
  • 5
  • [ 1128-56-9 ]
  • [ 26377-17-3 ]
  • 1-Phenyl-5-pyridin-4-yl-1H-pyrazolo[1,5-a]pyrimidin-7-one [ No CAS ]
  • 6
  • [ 1128-56-9 ]
  • [ 6283-81-4 ]
  • 1-Phenyl-5-pyridin-3-yl-1H-pyrazolo[1,5-a]pyrimidin-7-one [ No CAS ]
  • 7
  • [ 1128-56-9 ]
  • [ 638-07-3 ]
  • [ 88569-93-1 ]
  • 8
  • [ 1128-56-9 ]
  • [ 3044-06-2 ]
  • 2-ethoxycarbonyl-3-N-(1-phenyl-1H-pyrazol-3-yl)amino-2-butenoic acid, ethyl ester [ No CAS ]
  • 9
  • [ 1128-56-9 ]
  • [ 141-97-9 ]
  • [ 17436-80-5 ]
  • 10
  • [ 1128-56-9 ]
  • [ 141-97-9 ]
  • [ 75303-33-2 ]
  • [ 1155-15-3 ]
  • 11
  • [ 1128-56-9 ]
  • [ 94-02-0 ]
  • [ 64748-64-7 ]
YieldReaction ConditionsOperation in experiment
With PPA; ammonia; In water; a. 1,5-Diphenylpyrazolo[1,5-a]pyrimidin-7(1H)-one A mixture of 10 g. of 5-amino-2-phenylpyrazole (0.063 mol.), 12.1 g. of benzoylacetic acid ethyl ester (0.063 mol.) and 50 g. of polyphosphoric acid is heated at 110-120 with stirring for 90 minutes. After cooling, 200 ml. of water and then concentrated aqueous ammonia is added under external cooling to adjust the mixture to pH 9. The collected 1,5-diphenylpyrazolo[1,5-a]pyrimidin-7(1H)-one is washed with water and dried at 70, yield: 17 g. (94%); m.p. 194-200. A sample, recrystallized from absolute ethanol, melts at 205-207.
  • 13
  • [ 1128-56-9 ]
  • [ 98-59-9 ]
  • [ 92133-80-7 ]
  • 14
  • [ 1128-56-9 ]
  • [ 154229-52-4 ]
  • 2-ethoxycarbonyl-3-N-(1-phenyl-1H-pyrazol-3-yl)amino-2-pentenoic acid, ethyl ester [ No CAS ]
  • 15
  • [ 1128-56-9 ]
  • [ 87-13-8 ]
  • [ 87949-09-5 ]
  • 17
  • [ 871-29-4 ]
  • [ 100-63-0 ]
  • [ 1128-56-9 ]
  • 18
  • [ 2601-89-0 ]
  • [ 100-63-0 ]
  • [ 1128-56-9 ]
  • 19
  • [ 4554-16-9 ]
  • [ 100-63-0 ]
  • [ 1128-56-9 ]
  • 20
  • [ 100-63-0 ]
  • [ 920-37-6 ]
  • [ 1128-56-9 ]
YieldReaction ConditionsOperation in experiment
neutralization with 35% NaOH gave a precipitate which was filtered and washed with water.
EXAMPLE 7 Example 2 was repeated, with the only exception that the catalyst was composed of 0.1 g (0.000586 mole) of CuCl2.2H2 O and by 0.064 g (0.001 mole) of Cu, under an oxygen head. Oxidation was completed after about 3 hours. 3.8 g of 1-phenyl-3-aminopyrazole having a melting point of 89-90 were obtained.
Example 2 Preparation of 3-amino-1-phenylpyrazole A mixture of 3-aminopyrazole (1.0 g), cesium carbonate (4.32 g), cuprous oxide (86.1 mg), salicylaldoxime (330 mg), iodobenzene (2.58 g) and N,N-dimethylformamide (8 mL) was stirred under nitrogen atmosphere at 95 C. for 16 hours. The reaction solution obtained was allowed to cool to room temperature. Water and toluene were added thereto and the extraction was carried out. The organic phases obtained were combined and concentrated. The residue obtained was purified by silica gel column chromatography to give 3-amino-1-phenylpyrazole as yellowish orange oil (1.26 g). 1H-NMR (CDCl3) delta: 3.81 (br, 2H), 5.85 (d, J=1.8 Hz, 1H), 7.18 (t, J=8.4 Hz, 1H), 7.36-7.60 (m, 4H), 7.69 (d, J=1.6 Hz, 1H).
  • 23
  • [ 1128-56-9 ]
  • [ 268725-61-7 ]
  • 2-benzyl-5-(3-dimethylamino-propoxy)-2<i>H</i>-pyrazole-3-carboxylic acid (1-phenyl-1<i>H</i>-pyrazol-3-yl)-amide [ No CAS ]
  • 24
  • [ 1128-56-9 ]
  • [ 3612-20-2 ]
  • [ 425644-15-1 ]
  • 26
  • [ 1128-56-9 ]
  • [ 15761-38-3 ]
  • [1-(1-phenyl-1<i>H</i>-pyrazol-3-ylcarbamoyl)-ethyl]-carbamic acid <i>tert</i>-butyl ester [ No CAS ]
  • 27
  • [ 753482-69-8 ]
  • [ 1128-56-9 ]
  • 4-methyl-8-(morpholine-4-sulfonyl)-2-(1-phenyl-1<i>H</i>-pyrazol-3-yl)-pyrrolo[3,4-<i>c</i>]quinoline-1,3-dione [ No CAS ]
  • 28
  • [ 742103-27-1 ]
  • [ 1128-56-9 ]
  • n-allylpalladium chloride [ No CAS ]
  • [ 3756-32-9 ]
  • [ 1006707-95-4 ]
YieldReaction ConditionsOperation in experiment
In 5,5-dimethyl-1,3-cyclohexadiene; Example 6 Preparation of N-(1-phenylpyrazole-3-yl)-4-t-butylaniline A mixture of <strong>[1128-56-9]3-amino-1-phenylpyrazole</strong> (700 mg), 4-bromo-t-butylbenzene (1.02 g), sodium t-butoxide (465 mg), n-allylpalladium chloride (32.2 mg), di-t-butyl-(2,2-diphenyl-1-methylcyclopropyl) phosphine (124 mg) and xylene (20 mL) was stirred under a nitrogen atmosphere at 95 C. for 3 hours. The reaction solution was allowed to cool to room temperature. Then aqueous ammonium chloride-saturated solution was added thereto and the mixture was extracted with toluene. The organic phases obtained were combined and concentrated, and the residue obtained was purified by silica gel column chromatography to give N-(1-phenylpyrazole-3-yl)-4-t-butylaniline as a viscous oil (780 mg). 1H-NMR (CDCl3) delta: 1.27 (s, 9H), 6.11 (br, 1H), 6.17 (d, J=1.6 Hz, 1H), 7.16-7.66 (m, 9H), 7.80 (d, J=1.6 Hz, 1H).
  • 29
  • [ 742103-27-1 ]
  • [ 1128-56-9 ]
  • bis(π-allylpalladium chloride) [ No CAS ]
  • [ 1006707-92-1 ]
  • [ 3756-32-9 ]
  • [ 1006707-97-6 ]
YieldReaction ConditionsOperation in experiment
In 5,5-dimethyl-1,3-cyclohexadiene; Example 9 Preparation of N-(1-phenylpyrazole-3-yl)-N-(1-phenyl-1H-indazole-3-yl)-4-t-butylaniline A mixture of <strong>[1128-56-9]3-amino-1-phenylpyrazole</strong> (435 mg), 3-chloro-1-phenyl-1H-indazole (750 mg), sodium t-butoxide (630 mg), ?-allylpalladium chloride (45.0 mg), di-t-butyl-(2,2-diphenyl-1-methylcyclopropyl)phosphine (173 mg) and xylene (25 mL) was stirred under a nitrogen atmosphere at 95 C. for 3 hours. Then, 4-bromo-t-butylbenzene (582 mg) was added to the reaction mixture, further stirring at 95 C. for overnight. The reaction solution was allowed to cool to room temperature. Then aqueous ammonium chloride-saturated solution was added thereto and the mixture was extracted with toluene. The organic phases obtained were combined and concentrated, and the residue obtained was purified by silica gel column chromatography to give N-(1-phenylpyrazole-3-yl)-N-(1-phenyl-1H-indazole-3-yl)-4-t-butylaniline as a viscous oil (859 mg). 1H-NMR (CDCl3) delta: 1.35 (s, 9H), 6.33 (d, J=1.6 Hz, 1H), 6.97-7.09 (m, 2H), 7.25-7.40 (m, 9H), 7.49 (t, J=5.4 Hz, 2H), 7.57-7.61 (m, 2H), 7.71-7.76 (m, 3H), 7.86 (d, J=1.6 Hz, 1H).
  • 30
  • [ 742103-27-1 ]
  • [ 1128-56-9 ]
  • bis(π-allylpalladium chloride) [ No CAS ]
  • [ 1006707-99-8 ]
  • [ 1006707-98-7 ]
YieldReaction ConditionsOperation in experiment
In 5,5-dimethyl-1,3-cyclohexadiene; Example 11 Preparation of 3-(1-phenylpyrazole-3-yl)amino-1-phenyl-5-methylpyrazole A mixture of 3-trifluoromethanesulfonyloxy-5-methyl-1-phenylpyrazole (500 mg), <strong>[1128-56-9]3-amino-1-phenylpyrazole</strong> (obtained by above Example 2)(261 mg), sodium t-butoxide (164 mg), ?-allylpalladium chloride (23.8 mg), di-t-butyl-(2,2-diphenyl-1-methylcyclopropyl)-phosphine (91.8 mg) and xylene (20 mL) was stirred under a nitrogen atmosphere at 95 C. for 3 hours. The reaction solution was allowed to cool to room temperature. Then aqueous ammonium chloride-saturated solution was added thereto and the mixture was extracted with toluene. The organic phases obtained were combined and concentrated, and the residue obtained was purified by silica gel column chromatography to give 3-(1-phenylpyrazole-3-yl) amino-1-phenyl-5-methylpyrazole as a viscous oil (200 mg). 1H-NMR (CDCl3) delta: 2.35 (s, 3H), 6.25 (s, 1H), 6.33 (d, J=1.8 Hz, 1H), 6.58 (br, 1H), 7.20-7.50 (m, 8H), 7.62-7.67 (m, 2H), 7.79 (d, J=1.8 Hz, 1H).
  • 31
  • [ 1128-56-9 ]
  • IQMF-4 [ No CAS ]
  • 32
  • [ 1128-56-9 ]
  • 2-amino-<i>N</i>-(1-phenyl-1<i>H</i>-pyrazol-3-yl)-propionamide [ No CAS ]
  • 33
  • [ 1128-56-9 ]
  • [ 811473-54-8 ]
  • 34
  • [ 1128-56-9 ]
  • [ 425644-23-1 ]
  • 35
  • [ 1128-56-9 ]
  • N-(1-phenylpyrazol-3-yl)-N-(1-phenethyl-4-piperidyl)propanamide [ No CAS ]
 

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Technical Information

Categories

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