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Chemical Structure| 155600-99-0

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Product Details of [ 155600-99-0 ]

CAS No. :155600-99-0
Formula : C4H3Br2N3O2
M.W : 284.89
SMILES Code : O=[N+](C1=C(Br)N(C)N=C1Br)[O-]
MDL No. :MFCD09972218
InChI Key :PGMQVDHYFOWDLI-UHFFFAOYSA-N
Pubchem ID :22918638

Safety of [ 155600-99-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 155600-99-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 5
Fraction Csp3 0.25
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 47.71
TPSA ?

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

63.64 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.45
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

2.11
Log Po/w (WLOGP)?

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

1.85
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.

1.33
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

-0.18
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.31

Water Solubility

Log S (ESOL):?

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

-3.21
Solubility 0.177 mg/ml ; 0.000622 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.

-3.08
Solubility 0.239 mg/ml ; 0.000837 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

-1.88
Solubility 3.78 mg/ml ; 0.0133 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.

-6.54 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

2.0 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<0.0
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)

2.11

Application In Synthesis of [ 155600-99-0 ]

* 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 [ 155600-99-0 ]

[ 155600-99-0 ] Synthesis Path-Downstream   1~9

YieldReaction ConditionsOperation in experiment
Production example 1 3,5-dibromo-1-methyl-4-nitropyrazole In method II using methyl sulfate, 5.06 g (96 percent of theory) of 3,5-dibromo-1-methyl-4-nitropyrazole are obtained in the form of white crystals with a melting point of 154 C. 1 H-NMR (60 MHz, DMSO-d6):=3.90 ppm (s; 3H; --CH3). In this and in all of the following 1 H-NMR spectra: chemical shift is indicated in delta (ppm), the coupling constants (J) are indicated in Hertz. Standard: tetramethylsilane s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet, Ph=phenyl, ring-H=proton on pyrazole ring MS (70 eV): m/e=287 (M+).
  • 2
  • [ 155600-99-0 ]
  • [ 100-46-9 ]
  • [ 155601-07-3 ]
YieldReaction ConditionsOperation in experiment
In ethanol; water; Production example 9 5-benzylamino-3-bromo-1-methyl-4-nitropyrazole 2 g (7.02 mmoles) of <strong>[155600-99-0]3,5-dibromo-1-methyl-4-nitropyrazole</strong> are heated in a solution of 11 g (0.1 mole) of benzylamine in 50 ml ethanol for 10 hours at boiling temperature. After cooling, the reaction mixture is poured on 100 ml water, the separated product is filtered and washed with water (20 ml). After vacuum drying, 1.76 g (81 percent of theory) of 5-benzylamino-3-bromo-1-methyl-4-nitropyrazole are obtained in the form of yellow needles with a melting point of 133 C. 1 H-NMR (60 MHz, DMSO-d6):=7.88 (t; 1H; J=6 Hz; --NH; exchangeable with D2 O), 7.32 (m; 5H; Ph-H), 4,73 (d; 2H; J=6 Hz; --NH--CH2 --; s after exchanging with D2 O) and 3.68 ppm (s; 3H; N--CH3). MS (70 eV): m/e=312 (M+).
In dimethyl sulfoxide; Nucleophilic aromatic substitution of the compound 2 with benzylamine in DMSO produces benzyl-(5-bromo-2-methyl-4-nitro-2H-pyrazol-3-yl)-amine 3.
  • 3
  • [ 155600-99-0 ]
  • [ 155601-04-0 ]
YieldReaction ConditionsOperation in experiment
With methylamine; In ethanol; water; Production example 6 3-bromo-1-methyl-5-methylamino-4-nitropyrazole 2 g (7.02 mmoles) of <strong>[155600-99-0]3,5-dibromo-1-methyl-4-nitropyrazole</strong> are heated in 50 ml of a 40-percent solution of methylamine in ethanol for 4 hours at boiling temperature. After cooling, 100 ml water are added to the reaction mixture, the separated product is filtered out and washed with a small amount of water (20 ml). After vacuum drying, 1.45 g (88 percent of theory) of 3-bromo-1-methyl-5-methylamino-4-nitropyrazole are obtained in the form of yellow crystals with a melting point of 185 C. 1 H-NMR (60 MHz, DMSO-d6):=7.50 (s; wide; 1H; --NH; exchangeable with D2 O), 3.88 (s; 3H; N--CH3) and 3.16 ppm (d; 3H; J=6 Hz; --NH--CH3; s after exchanging with D2 O). MS (70 eV):m/e=236 (M+).
  • 4
  • [ 155600-99-0 ]
  • [ 155601-06-2 ]
YieldReaction ConditionsOperation in experiment
With tert-butylamine; In ethanol; water; Production example 8 3-bromo-5-tert-butylamino-1-methyl-4-nitropyrazole 1.5 g (5.26 mmoles) of <strong>[155600-99-0]3,5-dibromo-1-methyl-4-nitropyrazole</strong> are heated in a solution of 20 ml tert-butylamine in 30 ml ethanol for 20 hours at boiling temperature. After cooling, the reaction mixture is poured on 150 ml water, the separated product is filtered and washed with 100 ml water. After vacuum drying, 1.14 g (78 percent of theory) of 3-bromo-5-tert-butylamino-1-methyl-4-nitropyrazole are obtained in the form of pale yellow flakes with a melting point of 75 to 77 C. 1 H-NMR (60 MHz, DMSO-d6):=5.35 (s; 1H; --NH; exchanges with D2 O), 3.75 (s; 3H; N--CH3) and 1.20 ppm (s; 9H; --C(CH3)3). MS (70 eV): m/e=277 (M+).
  • 5
  • [ 155600-99-0 ]
  • [ 141-43-5 ]
  • [ 155601-05-1 ]
YieldReaction ConditionsOperation in experiment
In ethanol; water; Production example 7 3-bromo-5-(2'-hydroxyethylamino)-1-methyl-4-nitropyrazole 3 g (10.5 mmoles) of <strong>[155600-99-0]3,5-dibromo-1-methyl-4-nitropyrazole</strong> are heated in a solution of 30 ml ethanolamine in 30 ml ethanol for 15 hours at boiling temperature. The reaction mixture is then poured on 200 ml water, the separated product is filtered, washed with water (20 ml) and vacuum dried. Additional product crystallizes from the filtrate when cooled (5 C.). 2.25 g (81 percent of theory) of 3-bromo-5-(2'-hydroxyethyl)amino-1-methyl-4-nitropyrazole are obtained in the form of yellow crystals with a melting point of 150 C. 1 H-NMR (60 MHz, DMSO-d6): =7.38 (s; wide; 1H; --NH; exchangeable with D2 O), 4.98 (s; wide; 1H; --OH; exchangeable with D2 O), 3.82 (s; 3H; N--CH3) and 3.60 ppm (m; 4H; --NH --CH2 --CH2). MS (70 eV):m/e=266 (M+).
  • 6
  • [ 155600-99-0 ]
  • [ 100-46-9 ]
  • [ 452082-39-2 ]
YieldReaction ConditionsOperation in experiment
In dimethyl sulfoxide; Nucleophilic aromatic substitution of the compound 2 with benzylamine in DMSO produces benzyl-(5-bromo-2-propyl-4-nitro-2H-pyrazol-3-yl)-amine 3.
  • 7
  • [ 155600-99-0 ]
  • 3,5-dibromo-1-methyl-4-nitropyzole [ No CAS ]
  • [ 100-46-9 ]
  • [ 155601-07-3 ]
YieldReaction ConditionsOperation in experiment
96% Preparation of N-benzyl-3-bromo-1-methyl-4-nitro-1H-pyrazol-5-amine (3) 3,5-dibromo-1-methyl-4-nitropyzole 2 (2.85 g 10 mmol) was heated in a solution of 10 mL of benzylamine for 6 h at 80 C. After cooling to room temperature, the reaction mixture was poured into water and the yellow solid formed. Then it was filtered, washed with water, dried and recrystallized from toluene to afford 3 g of 3 in yield of 96%.
  • 8
  • [ 104599-36-2 ]
  • [ 155600-99-0 ]
YieldReaction ConditionsOperation in experiment
72.6% With CH3I; In N,N-dimethyl-formamide; Example A 4,5-Diamino-1-methyl-1H-pyrazole-3-carbonitrile, obtainable from the following synthesis strategy: Preparation of 3,5-dibromo-1-methyl-4-nitro-1H-pyrazole (2): To a solution of 3,5-dibromo-4-nitropyrazole 1 (0.934 g, 3.45 mmol) in 5 mL of absolute DMF were added dropwise 0.16 g of sodium hydride (6.67 mmol) in DMF (100 mL) over a period of 1 h. After cessation of gas generation, 0.26 mL of CH3I (3.89 mmole) was added dropwise and stirred at room temperature for overnight. The solvent was then evaporated under vacuum and the residue was poured into water, The separated solid was filtered, washed with water and dried under vacuum to afford 0.713 g of 2 (yield 72.6%).
With NaH; methyl iodide; In N,N-dimethyl-formamide; Example F 1-Methyl-3-phenoxy-1H-pyrazole-4,5-diamine, obtainable from the following synthetic strategy: Treatment of 3,5-dibromo-4-nitro-1H-pyrazole 1 with MeI and NaH in DMF affords 3,5-dibromo-1-methyl-4-nitro-1H-pyrazole 2.
  • 9
  • 1-bromo-4-nitropyrazole [ No CAS ]
  • [ 77-78-1 ]
  • [ 155600-99-0 ]
  • [ 89607-15-8 ]
  • [ 89607-13-6 ]
  • [ 3994-50-1 ]
 

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Technical Information

Categories

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