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Chemical Structure| 89607-15-8

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Product Details of [ 89607-15-8 ]

CAS No. :89607-15-8
Formula : C4H4BrN3O2
M.W : 206.00
SMILES Code : O=[N+](C1=CN(C)N=C1Br)[O-]
MDL No. :MFCD00466335
InChI Key :BHFRSRAZJCLLDY-UHFFFAOYSA-N
Pubchem ID :13185127

Safety of [ 89607-15-8 ]

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

Computational Chemistry of [ 89607-15-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
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 40.01
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.

1.3
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

1.09
Log Po/w (WLOGP)?

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

1.09
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.

0.52
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

-0.94
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.61

Water Solubility

Log S (ESOL):?

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

-2.11
Solubility 1.61 mg/ml ; 0.0078 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.

-2.02
Solubility 1.97 mg/ml ; 0.00958 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

-1.04
Solubility 19.0 mg/ml ; 0.092 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.

-6.78 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<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)

2.03

Application In Synthesis of [ 89607-15-8 ]

* 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 [ 89607-15-8 ]

[ 89607-15-8 ] Synthesis Path-Downstream   1~7

  • 1
  • 1-bromo-4-nitropyrazole [ No CAS ]
  • [ 77-78-1 ]
  • [ 155600-99-0 ]
  • [ 89607-15-8 ]
  • [ 89607-13-6 ]
  • [ 3994-50-1 ]
  • 2
  • [ 20055-00-9 ]
  • [ 89607-15-8 ]
YieldReaction ConditionsOperation in experiment
With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 0 - 25℃; for 2h; Step 4: Into a 250 mL round bottom flask containing a solution of copper(II) bromide (3.0 g, 14 mmol) and tert-butyl nitrite (1.7 mL, 14 mmol) in acetonitrile (150 mL) was added 1-methyl-4- nitro-1H-pyrazol-3-amine (2 g, 14 mmol) in acetonitrile (20 mL) at 0 C and the reaction was stirred at room temperature for 2 h. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (120 mL), washed with water and brine,dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Theresidue was purified by column chromatography eluting with ethyl acetate in petroleum ether(20-30%) to afford 3-bromo-1-methyl-4-nitro-1H-pyrazole as a solid. ?H NMR (CDC13, 300MHz): 5 8.25 (s, 1H), 3.89 (s, 3H).
With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 0 - 25℃; for 2.08333h; Step 3: A mixture of copper(II) bromide (5.5 g, 25 mmol) and tert-butyl nitrite (2.5 g, 25 mmol) in acetonitrile (100 mL) was taken into a 250 mL round bottom flask and cooled to 0 C. Asolution of 1-methyl-4-nitro-1H-pyrazol-3-amine (3.5 g, 25 mmol) in acetonitrile (20 mL) was added dropwise over a period of 5 mm. The reaction mixture was slowly warmed to room temperature and stirred for 2 h. The reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography eluting with ethyl acetate in petroleum ether (15-20%) to afford 3-bromo-1-methyl-4-nitro-1H-pyrazole as a solid. ?H NMR (DM50-cl6, 400 MHz): 8.94 (s, 1H), 3.89 (s, 3H).
With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 0 - 20℃; for 2h; Stpe 4: Into a 250 mL round bottom flask containing a solution of copper(II) bromide (3.0 g, 14 mmol) and fert-butyl nitrite (1.7 mL, 14 mmol) in acetonitrile (150 mL) was added l-methyl-4- nitro-lH-pyrazol-3-amine (2 g, 14 mmol) in acetonitrile (20 mL) at 0 C and the reaction was stirred at room temperature for 2 h. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (120 mL), washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography eluting with ethyl acetate in petroleum ether (20-30%) to afford 3-bromo-l-methyl-4-nitro-lH-pyrazole as a solid. NMR (CDC13, 300 MHz): delta 8.25 (s, 1H), 3.89 (s, 3H).
With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 0 - 20℃; for 2h; Step 4: Into a 250 mL round bottom flask containing a solution of copper(II) bromide (3.0 g, 14 mmol) and tert-butyl nitrite (1.7 mL, 14 mmol) in acetonitrile (150 mL) was added 1-methyl-4- nitro-1H-pyrazol-3-amine (2 g, 14 mmol) in acetonitrile (20 mL) at 0 oC and the reaction was stirred at room temperature for 2 h. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (120 mL), washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography eluting with ethyl acetate in petroleum ether (20-30%) to afford 3-bromo-1-methyl-4-nitro-1H-pyrazole as a solid. 1H NMR (CDCl3, 300 MHz): delta 8.25 (s, 1H), 3.89 (s, 3H).

  • 3
  • [ 89607-15-8 ]
  • 3-bromo-1-methyl-1H-pyrazol-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogen; In ethyl acetate; at 25℃; for 16h; Step 5: Into a 100 mL round bottom flask containing a solution of <strong>[89607-15-8]3-bromo-1-methyl-4-nitro-1H-pyrazole</strong> (1.0 g) in ethyl acetate (50 mL) at room temperature was added Raney Nickel (700mg) and the reaction mixture was stirred at room temperature for 16 h under hydrogen atmosphere. The reaction mixture was filtered through celite and washed with ethyl acetate. The filtrate was concentrated under reduced pressure and purified by flash chromatography eluting with ethyl acetate in petroleum ether (40-50%) to afford 3-bromo-1-methyl-1H-pyrazol- 4-amine as a liquid. ?H NMR (CD3OD, 400 MHz): 5 7.18 (s, 1H), 3.77 (s, 3H). MS calc?d [M+Hj 176.0, found 176.2.
With hydrogen; In ethyl acetate; at 25℃; for 16h; Step 5: Into a 100 mL round bottom flask containing a solution of <strong>[89607-15-8]3-bromo-1-methyl-4-nitro-1H-pyrazole</strong> (1.0 g) in ethyl acetate (50 mL) at room temperature was added Raney Nickel (700mg) and the reaction mixture was stirred at room temperature for 16 h under hydrogen atmosphere. The reaction mixture was filtered through celite and washed with ethyl acetate. The filtrate was concentrated under reduced pressure and purified by flash chromatography eluting with ethyl acetate in petroleum ether (40-50%) to afford 3-bromo-1-methyl-1H-pyrazol- 4-amine as a liquid. ?H NMR (CD3OD, 400 MHz): 7.18 (s, 1H), 3.77 (s, 3H). MS calc?d[M+Hj 176.0, found 176.2.
With hydrogen; In ethyl acetate; at 20℃; for 16h; Stpe 5: Into a 100 mL round bottom flask containing a solution of 3-bromo-l-methyl-4-nitro- lH-pyrazole (1.0 g) in ethyl acetate (50 mL) at room temperature was added Raney Nickel (700 mg) and the reaction mixture was stirred at room temperature for 16 h under hydrogen atmosphere. The reaction mixture was filtered through celite and washed with ethyl acetate. The filtrate was concentrated under reduced pressure and purified by flash chromatography eluting with ethyl acetate in petroleum ether (40-50%) to afford 3-bromo-l -methyl- lH-pyrazol- 4-amine as a liquid. 1 NMR (CD3OD, 400 MHz): delta 7.18 (s, 1H), 3.77 (s, 3H). MS calc'd [M+H]+ 176.0, found 176.2.
With hydrogen; In ethyl acetate; at 20℃; for 16h; Step 5: Into a 100 mL round bottom flask containing a solution of 3-bromo-1-methyl-4-nitro- 1H-pyrazole (1.0 g) in ethyl acetate (50 mL) at room temperature was added Raney Nickel (700 mg) and the reaction mixture was stirred at room temperature for 16 h under hydrogen atmosphere. The reaction mixture was filtered through celite and washed with ethyl acetate. The filtrate was concentrated under reduced pressure and purified by flash chromatography eluting with ethyl acetate in petroleum ether (40-50%) to afford 3-bromo-1-methyl-1H-pyrazol-4-amine as a liquid. 1H NMR (CD3OD, 400 MHz): delta 7.18 (s, 1H), 3.77 (s, 3H). MS calc?d [M+H]+ 176.0, found 176.2

  • 4
  • [ 7486-35-3 ]
  • [ 89607-15-8 ]
  • 1-methyl-4-nitro-3-vinyl-1H-pyrazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); In toluene; at 120℃; for 6h; Step 4: Into a 25 mL round bottom flask containing a solution of 3-bromo-1-methyl-4-nitro-1H- pyrazole (1.0 g, 5 mmol) in toluene (5 mL) were added tributyl(vinyl)tin (1.7 mL, 58 mmol) andtetrakis(triphenylphosphine)palladium(0) (300 mg, 0.25 mmol) and the reaction was heated at120 C for 6 h. The reaction mixture was cooled to room temperature, concentrated and purifiedby flash chromatography eluting with ethyl acetate in petroleum ether (15-20%) to afford 1-methyl-4-nitro-3-vinyl-1H-pyrazole as a solid. ?H NMR (CDC13, 300 MHz): 8.07 (s, 1H), 7.22(dd,J= 17.6, 11.2 Hz, 1H), 6.19 (dd,J= 17.7, 4.6 Hz, 1H), 5.54(dd,J= 11.1, 1.6 Hz, 1H), 3.97(s, 3H).
  • 5
  • [ 89607-15-8 ]
  • [ 1692-15-5 ]
  • 4-(1-methyl-4-nitro-1H-pyrazol-3-yl)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 80℃; for 14h;Sealed tube; Inert atmosphere; Step 1: Into a 10 mL sealed tube containing a solution of 3-bromo-1-methyl-4-nitro-JH-pyrazole (800 mg, 0.4 mmol) in 1,4-dioxane (2 mL) were added potassium phosphate tribasic (140 mg,0.7 mmol) in water (1 mL) and pyridin-4-ylboronic acid (70 mg, 0.6 mmol) and the mixture was degassed with nitrogen for 10 mm. [1,1?-bis(diphenylphosphino)ferrocenej dichloropalladium(II),complex with dichloromethane (20 mg, 0.03 mmol) was added and the reaction mixture was heated at 80 C for 14 h. The reaction mixture was filtered thorugh celite and the filterate was concentrated under reduced pressure.The residue was purified by flash chromatography eluting with ethyl acetate in petroleum ether (10-15%) to yield 4-(1-methyl-4-nitro-1H-pyrazol-3-yl)pyridine. ?H NMR (DMSO-d6, 300 MHz): oe 8.98 (s, 1H), 8.67 (d, J 6.1 Hz, 2H), 7.62 (d, J 6.1 Hz, 2H), 3.95 (s, 3H). MS calc?d [M+Hj 205.1, found 205.2.
  • 6
  • [ 784193-37-9 ]
  • [ 74-88-4 ]
  • [ 89607-15-8 ]
YieldReaction ConditionsOperation in experiment
58% With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h; To a mixture of 3-bromo-4-nitro-1H-pyrazole (6.20 g, 32.3 mmol) and K2CO3 (5.36 g, 38.7 mmol) in DMF (40 mL) was added MeI (5.50 g, 38.7 mmol) at 0 C. Then, the mixture was stirred at 25 C. for 2 hours. On completion, the mixture was diluted with water (200 mL), then extracted with EA (3×80 mL). The combined organic layer was washed with brine (50 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography over silica gel (PE:EA=20:1-3:1) to give the title compound (3.90 g, 58% yield) as light yellow solid. 1H NMR (400 MHz, CDCl3) delta 8.16 (s, 1H), 3.97 (s, 3H).
  • 7
  • [ 89607-15-8 ]
  • methyl 5-(1-methyl-4-nitropyrazol-3-yl)pyridine-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium hydrogencarbonate; In 1,4-dioxane; dichloromethane; water; at 80℃; for 2h;Inert atmosphere; A mixture of 3-bromo-1-methyl-4-nitro-pyrazole (3.80 g, 18.4 mmol), (5-methoxycarbonyl-3-pyridyl)boronic acid (4.67 g, 25.8 mmol, CAS871329-53-2), Pd(dppf)Cl2.CH2Cl2 (800 mg, 979 umol) and NaHCO3 (3.10 g, 36.8 mmol) in dioxane (50 mL) and H2O (10 mL) was stirred at 80 C. under N2 for 2 hours. On completion, the mixture was cooled to 25 C. The mixture was diluted with water (100 mL), then extracted with EA (3×80 mL). The combined organic layer was washed with brine (50 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (PE:EA=5:1-DCM:EA=2:1) to give the title compound (2.95 g, 61% yield) as light yellow solid. 1H NMR (400 MHz, CDCl3) delta 9.29 (s, 1H), 9.12 (s, 1H), 8.68 (s, 1H), 8.31 (s, 1H), 4.05 (s, 3H), 4.00 (s, 3H).
 

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Technical Information

Categories

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