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Chemical Structure| 288246-16-2 Chemical Structure| 288246-16-2

Structure of 288246-16-2

Chemical Structure| 288246-16-2

4-Bromo-1H-pyrazole-5-carbonitrile

CAS No.: 288246-16-2

4.5 *For Research Use Only !

Cat. No.: A178554 Purity: 97%

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Product Details of [ 288246-16-2 ]

CAS No. :288246-16-2
Formula : C4H2BrN3
M.W : 171.98
SMILES Code : N#CC1=C(Br)C=NN1
MDL No. :MFCD00105683
InChI Key :ZXVFKQRZKKGVNJ-UHFFFAOYSA-N
Pubchem ID :2735623

Safety of [ 288246-16-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 288246-16-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 31.0
TPSA ?

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

52.47 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.72
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

0.96
Log Po/w (WLOGP)?

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

1.04
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.

-0.17
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

1.7
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.85

Water Solubility

Log S (ESOL):?

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

-1.97
Solubility 1.83 mg/ml ; 0.0106 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.

-1.65
Solubility 3.86 mg/ml ; 0.0224 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

-2.17
Solubility 1.17 mg/ml ; 0.00678 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.

-6.67 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

2.0
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)

1.8

Application In Synthesis of [ 288246-16-2 ]

* 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 [ 288246-16-2 ]

[ 288246-16-2 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 110-87-2 ]
  • [ 288246-16-2 ]
  • [ 957346-02-0 ]
YieldReaction ConditionsOperation in experiment
40% Step 1 4-Bromo-2-(tetrahydro-pyran-2-yl) -2H-pyrazole-3-carboniotatriotaleBr /N NV-O / /[00412] 4-Bromo-lH-pyrazole-3-carbomt?le (150mg, 0 87mmol) is dissolved in 3,4-dihydro-2H-pyran (25 mL, 2 6mmol) in the presence of a catalytic amount of TFA (lmg, 0 009mmol) The reaction mixture is stirred at 950C for 1 hour, cooled and then quenched using NaH (1 2mg, 0 052mmol) After removing the solvent, the residue is pu?fied by silica gel column chromatography elutmg with a mixture of 3 1 petroleum ether-dichloromethane, followed by 10 1 petroleum ether-ethyl acetate The fractions containing the desired compounds are collected and concentrated in vacuo to afford the title compound as a colorless oil (90mg, 40%)
  • 2
  • [ 288246-16-2 ]
  • [ 451-46-7 ]
  • [ 1072198-59-4 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2.0h; Example 3; 4-(4-Bromo-3-cyanopyrazole-1-yl)benzoic acid ethyl ester; A suspension of <strong>[288246-16-2]4-bromo-1H-pyrazole-3-carbonitrile</strong> (0.52 g), 4-fluoro-benzoic acid ethyl ester (0.56 g) and cesium carbonate (1.5 g) in N,N-dimethylformamide (10 mL) was stirred at 100C for 2 hours. After cooling to ambient temperature, this reaction mixture was poured into water, and this mixture was extracted with ethyl acetate. This organic layer was washed with brine, dried over anhydrous magnesium sulfate. The organic layer was through an aminopropyl silica gel, and this filtrate was concentrated under reduced pressure. This obtained residue was washed with a mixed solvent of n-hexane/diethyl ether = 5/1 to give the title compound (0.25 g).
  • 3
  • [ 288246-16-2 ]
  • 2,5-difurorboronic acid [ No CAS ]
  • C10H4BrF2N3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
25% With pyridine; copper diacetate; at 20℃; for 72.0h;Molecular sieve; To a solution of 4-bromo-3-cyano-lH-pyrazole 49 (172 mg, 1 mmol) in pyridine (3 mL) was added 2,5-difluorophenyl boronic acid (237 mg, 1.5 mmol), and 4A molecular sieves. The mixture was stirred for 72 h at room temperature. The reaction was worked-up with saturated NaHC0 and EtOAc extraction. The organic layer was separated and aqueous was extracted with EtOAc. The combined organic phase was dried over a2S04, filtered, and concentrated to give crude product. The crude product was purified on ISCO columns. Fractions containing pure product were combined and evaporated to give 50 (70 mg, 25%) as a blue wax.
  • 4
  • [ 288246-16-2 ]
  • [ 5664-17-5 ]
  • (S)-4-bromo-1-(1-cyclohexylallyl)-1H-pyrazole-3-carbonitrile [ No CAS ]
  • (R)-4-bromo-1-(1-cyclohexylallyl)-1H-pyrazole-3-carbonitrile [ No CAS ]
  • 5
  • [ 288246-16-2 ]
  • [ 5664-17-5 ]
  • 4-bromo-1-(1-cyclohexylallyl)-1H-pyrazole-3-carbonitrile [ No CAS ]
  • 6
  • [ 288246-16-2 ]
  • 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine [ No CAS ]
  • 4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazole-3-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; at 20 - 100℃;Inert atmosphere; At room temperature, compound (36c) (1.63 g, 4.36 mmol), <strong>[288246-16-2]4-bromo-1H-pyrazole-3-carbonitrile</strong> (36d) (500 mg,2.91 mmol), a potassium carbonate (1.00 g, 7.28 mmol) solution (10 mL) and 1,4-dioxane (50 mL) were sequentiallyadded to a 150 mL reaction flask, and nitrogen atmosphere protection was applied. After the reaction solution was stirreduntil homogenous, Pd(dppf)Cl2 (213 mg, 0.29 mmol) was added under protection of nitrogen. The system was heatedto 100C, and the reaction was allowed to proceed overnight. After thin layer chromatography indicated the reactionwas complete, the reaction solution was quenched with water, extracted with ethyl acetate, dried over anhydrous sodiumsulfate, concentrated under reduced pressure, and purified by column chromatography on silica gel, to afford compound(36e) (255 mg, white solid), yield: 26%. MS (ESI, m/z): 340 [M+H]+.
  • 7
  • [ 288246-16-2 ]
  • [ 104367-27-3 ]
  • (E)-4-bromo-1-(1,7-diphenylhept-4-en-3-yl)-1H-pyrazole-3-carbonitrile [ No CAS ]
  • (S,E)-4-bromo-1-(1,7-diphenylhept-4-en-3-yl)-1H-pyrazole-3-carbonitrile [ No CAS ]
  • (S,E)-4-bromo-1-(1,7-diphenylhept-4-en-3-yl)-1H-pyrazole-5-carbonitrile [ No CAS ]
  • 8
  • [ 288246-16-2 ]
  • [ 104367-27-3 ]
  • (S,E)-4-bromo-1-(1,7-diphenylhept-4-en-3-yl)-1H-pyrazole-3-carbonitrile [ No CAS ]
  • (S,E)-4-bromo-1-(1,7-diphenylhept-4-en-3-yl)-1H-pyrazole-5-carbonitrile [ No CAS ]
  • 9
  • [ 288246-16-2 ]
  • (3S,6R,9S,12R,15S,18R,21S,24R)-6,18-bis[[4-(chloromethyl)phenyl]methyl]-3,9,15,21-tetraisobutyl-4,10,12,16,22,24-hexamethyl-1,7,13,19-tetraoxa-4,10,16,22-tetrazacyclotetracosane-2,5,8,11,14,17,20,23-octaone [ No CAS ]
  • 1,1'-(((((2R,5S,8R,11S,14R,17S,20R,23S)-5,11,17,23-tetraisobutyl-4,8,10,16,20,22-hexamethyl-3,6,9,12,15,18,21,24-octaoxo-1,7,13,19-tetraoxa-4,10,16,22-tetraazacyclotetracosane-2,14-diyl)bis(methylene))bis(4,1-phenylene))bis(methylene))bis(4-bromo-1H-pyrazole-3-carbonitrile) [ No CAS ]
YieldReaction ConditionsOperation in experiment
46 mg With potassium carbonate; potassium iodide; In acetonitrile; at 50℃; for 48.0h; was prepared: to a solution of Bis-CFhCI PF1022a in acetonitrile (4.8 ml_, 0.02M) was 4-bromo-1 H-pyrazole-3-carbonitrile added (66 mg, 0.38 mmol), potassium bicarbonate (38 mg, 0.38 mmol) and potassium iodide (95 mg, 0.57 mmol). The mixture was heated to 50C for 48 hours. After cooling to room temperature, the solvent was removed under reduced pressure and the residue partitioned between water and DCM. The organics were separated, dried over MgS04 and evaporated. The crude material was purified by reverse phase HPLC to give the title product as a white solid (46 mg).
 

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