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Chemical Structure| 773887-09-5 Chemical Structure| 773887-09-5

Structure of 773887-09-5

Chemical Structure| 773887-09-5

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Product Details of [ 773887-09-5 ]

CAS No. :773887-09-5
Formula : C10H11BrN2
M.W : 239.11
SMILES Code : CC(C)C1=C2NN=CC2=CC(Br)=C1
MDL No. :MFCD13177024
InChI Key :WHZLVUPLAGPFMC-UHFFFAOYSA-N
Pubchem ID :21102197

Safety of [ 773887-09-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 773887-09-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 9
Fraction Csp3 0.3
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 58.37
TPSA ?

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

28.68 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.02
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

3.37
Log Po/w (WLOGP)?

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

3.45
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.

2.78
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

3.61
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.04

Water Solubility

Log S (ESOL):?

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

-3.89
Solubility 0.0307 mg/ml ; 0.000128 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.

-3.65
Solubility 0.0535 mg/ml ; 0.000224 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

-4.59
Solubility 0.0061 mg/ml ; 0.0000255 mol/l
Class?

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

Moderately 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.

-5.37 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

0.0
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)

1.87

Application In Synthesis of [ 773887-09-5 ]

* 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 [ 773887-09-5 ]

[ 773887-09-5 ] Synthesis Path-Downstream   1~10

YieldReaction ConditionsOperation in experiment
4.2 g (74%) 5-Bromo-7-isopropyl-1H-indazole A flame-dried round bottom flask was charged with 4-bromo-2,6-diethylphenyldiazo-t-butyl sulfide (7.94 g, 24 mmol) and potassium t-butoxide (27 g, 10 equiv). A stir bar was added and the mixture placed under nitrogen. To this was added dry dimethylsulfoxide (70 mL). The mixture was stirred vigorously overnight at room temperature. The reaction mixture was carefully poured into a mixture of crushed ice (250 mL) and 10% hydrochloric acid (120 mL). The resulting suspension was collected by filtration and washed severally with water. The solid was collected and dried in vacuo to give 4.2 g (74%) of the desired product. LC/MS: tR=1.73 min, 241.06 (MH)+.
  • 2
  • [ 773887-09-5 ]
  • [ 773887-11-9 ]
YieldReaction ConditionsOperation in experiment
2.1 g (92%) With hydrogenchloride; sec.-butyllithium; sodium hydrogencarbonate; In tetrahydrofuran; N-methyl-acetamide; cyclohexane; 7-Isopropyl-1H-indazole-5-carbaldehyde <strong>[773887-09-5]5-Bromo-7-isopropyl-1H-indazole</strong> (3.1 g, 12.1 mmol) and sodium hydride (0.34 g, 1.1 equiv.) were weighed into a flame-dried round-bottom flask containing a magnetic stir bar. Under a nitrogen atmosphere at room temperature, dry tetrahydrofuran (18 mL) was added. The mixture was stirred at room temperature for 15 min, during which time it became homogeneous. The stirred mixture was cooled to -78 C. and a solution of sec-butyllithium in cyclohexane (1.4M, 20 mL, 2.2 equiv.) was added over several minutes. After 1 h at -78 C., dimethylformamide (3.0 mL) was slowly added and the mixture allowed to warm to room temperature overnight. The solution was cooled to 0 C. and carefully treated with 1 N hydrochloric acid (35 mL). After a few minutes, solid sodium bicarbonate was added until a pH of 9-10 was attained. The two layers were separated and the aqueous phase washed twice with ethyl acetate. The combined organic layers were washed with water (2*), brine (2*), dried over sodium sulfate, and concentrated. Column chromatography gave 2.1 g (92%) of pure material. LC/MS: tR=1.15 min, 189.12 (MH)+.
  • 3
  • [ 773887-09-5 ]
  • [ 68-12-2 ]
  • [ 773887-11-9 ]
  • 4
  • [ 773887-07-3 ]
  • [ 773887-09-5 ]
YieldReaction ConditionsOperation in experiment
58.1% With acetic acid; sodium nitrite; In water; Compound 15b (1.1 g, 4.8 mmol) was dissolved in 15 mL of acetic acid, and 2 mL of sodium nitrite (400 mg,Aqueous solution of 5.8 mmol) was stirred overnight. After the reaction solution is concentrated, a saturated sodium hydrogencarbonate solution is added.Ethyl acetate (20 mL × 3) was extracted, and the organic phase was combined, washed with saturated sodium chloride and dried over sodium sulfate.Concentrated under reduced pressure,The residue was purified by eluent system B using a CombiFlash rapid preparation apparatus.The title product 15c (670 mg, yield: 58.1%) was obtained.
  • 5
  • C14H21BrN2 [ No CAS ]
  • [ 773887-09-5 ]
  • 6
  • [ 773887-09-5 ]
  • [ 773887-13-1 ]
  • 7
  • [ 773887-09-5 ]
  • [ 773887-15-3 ]
  • 8
  • [ 5266-85-3 ]
  • [ 773887-09-5 ]
  • 9
  • [ 773887-09-5 ]
  • C19H18N6 [ No CAS ]
  • 10
  • [ 773887-09-5 ]
  • [ 73183-34-3 ]
  • 7-isopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
75.1% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100.0℃; for 3.0h;Inert atmosphere; Compound 15c (400 mg, 1.67 mmol), Compound 1b (638 mg, 2.51 mmol),[1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (122 mg, 0.17 mmol) and potassium acetate (492 mg, 5.02 mmol)The mixture was separately added to 20 mL of 1,4-dioxane, and reacted at 100 C for 3 hours. Diatomaceous earth filtration,Ethyl acetate (20 mL × 2) was washed and concentrated under reduced pressure.The residue was purified by eluent system B using a CombiFlash rapid preparation apparatus.The title product 15d (360 mg, yield: 75.1%) was obtained.
 

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Technical Information

Categories

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[ 773887-09-5 ]

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[ 773887-09-5 ]

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