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Chemical Structure| 99365-48-7 Chemical Structure| 99365-48-7

Structure of 99365-48-7

Chemical Structure| 99365-48-7

4-Bromooxindole

CAS No.: 99365-48-7

4.5 *For Research Use Only !

Cat. No.: A389690 Purity: 97%

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Product Details of [ 99365-48-7 ]

CAS No. :99365-48-7
Formula : C8H6BrNO
M.W : 212.04
SMILES Code : C2=C1NC(CC1=C(Br)C=C2)=O
MDL No. :MFCD06659911
InChI Key :XQQPPAZTHUEMPF-UHFFFAOYSA-N
Pubchem ID :2763190

Safety of [ 99365-48-7 ]

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

Computational Chemistry of [ 99365-48-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 49.43
TPSA ?

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

29.1 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.72
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

1.46
Log Po/w (WLOGP)?

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

1.37
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.

1.87
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

2.53
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.79

Water Solubility

Log S (ESOL):?

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

-2.48
Solubility 0.705 mg/ml ; 0.00333 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.

-1.68
Solubility 4.46 mg/ml ; 0.021 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

-3.75
Solubility 0.0379 mg/ml ; 0.000179 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.

-6.56 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)

1.7

Application In Synthesis of [ 99365-48-7 ]

* 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.

  • Upstream synthesis route of [ 99365-48-7 ]
  • Downstream synthetic route of [ 99365-48-7 ]

[ 99365-48-7 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 99365-48-7 ]
  • [ 73183-34-3 ]
  • [ 1150271-44-5 ]
YieldReaction ConditionsOperation in experiment
74% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In 1,4-dioxane at 110℃; for 2 h; Sealed tube; Microwave irradiation Intermediate 114: 4-(4,4,5,5-Tetramethyl-1 ,2-dioxaborolan-2-yl)indolin-2-one (0793) A mixture of 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(l,3,2-dioxaborolane) (1.903 g, 7.49 mmol, commercially available from, for example, Fluorochem), 4-bromoindolin-2-one (1.038 g, 4.90 mmol, commercially available from, for example, Fluorochem), [1,1'- 7 s(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane [Pd(dppf)Cl2.DCM] (0.601 g, 0.73 mmol) and potassium acetate (1.480 g, 15.08 mmol) in 1,4-dioxane (30 mL) was stirred at 110 °C for 2 h. The mixture was allowed to cool to rt before being filtered through a 10 g celite cartridge. The cartridge was washed through with ethyl acetate (3 x 30 mL) and the combined filtrates were evaporated in vacuoto give a brown liquid which was re-dissolved in DCM (ca. 10 mL), loaded onto a 100 g SNAP silica cartridge and purified by Biotage SP4 semi-automated flash column chromatography eluting with a gradient of 20 to 50percent ethyl acetate in cyclohexane. The required fractions were combined and evaporated in vacuo, this was re-dissolved in DCM (ca. 10 mL), transferred to a tarred vial and the solvent evaporated under a stream of nitrogen. The residue was triturated with ether (5 x 5 mL), decanting away the mother liquor each time, and the residue dried under a stream of nitrogen and in vacuo to give the desired product 4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)indolin-2-one (941.8 mg, 3.63 mmol, 74 percent yield) as a cream solid. (0794) LCMS (2 min Formic): Rt = 0.93 min, [MH]+ = 260.3.
74.2% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In 1,4-dioxane at 110℃; for 2 h; A mixture of 4,4,4T,4T,5,5,5T,5T-octamethyl-2,2T-bi( 1,3, 2-d ioxaborolane) (1.9025 g, 7.49 mmol), 4-bromoindolin-2-one (1.0383 g, 4.90 mmol), [1,1’-Bis(d iphenylphosphino)ferrocene]dichloropallad ium(II), complex with dichloromethane (0.6005 g,0.734 mmol) and potassium acetate (1.4802 g, 15.08 mmol) in 1,4-Dioxane (30 mL) was stirred at110 °C for 2 hr. The mixture was allowed to cool to room temperature before being filtered througha lOg celite cartridge. The cartridge was washed through with ethyl acetate (3 x 30 mL) and thecombined filtrates were evaporated in vacuo to give to give a brown liquid, which was redissolved indichloromethane (ca. 10 mL), loaded onto a bOg SNAP silica cartridge and purified by Biotage 5P4semi-automated flash column chromatography eluting with a gradient of 20 to 50percent ethyl acetate incyclohexane. The required fractions were combined and evaporated in vacuo, the residue (which was on the verge of crystallisation) was re-dissolved in dichloromethane (ca. 10 mL), transferred to a tared vial, the solvent evaporated under a stream of nitrogen. The residue was triturated with ether (5 x 5 mL), decanting away the mother liquor each time, and the residue dried under a stream of nitrogen and in vacuoto give the desired product as a cream solid (941.8 mg, 3.63 mmol, 74.2 percent yield)LCMS (2 mm Formic): Rt = 0.93 mi [MH]+ = 260
References: [1] Patent: WO2017/174621, 2017, A1, . Location in patent: Page/Page column 88.
[2] Patent: WO2017/202742, 2017, A1, . Location in patent: Page/Page column 42; 43; 97; 98.
 

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