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Chemical Structure| 367-24-8 Chemical Structure| 367-24-8
Chemical Structure| 367-24-8

4-Bromo-2-fluoroaniline

CAS No.: 367-24-8

4.5 *For Research Use Only !

Cat. No.: A155079 Purity: 97%

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Product Details of [ 367-24-8 ]

CAS No. :367-24-8
Formula : C6H5BrFN
M.W : 190.01
SMILES Code : NC1=CC=C(Br)C=C1F
MDL No. :MFCD00010221

Safety of [ 367-24-8 ]

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

Calculated chemistry of [ 367-24-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 38.5
TPSA ?

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

26.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.71
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

2.13
Log Po/w (WLOGP)?

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

2.6
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.

2.67
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

2.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.27

Water Solubility

Log S (ESOL):?

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

-2.85
Solubility 0.266 mg/ml ; 0.0014 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.

-2.31
Solubility 0.935 mg/ml ; 0.00492 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

-3.17
Solubility 0.128 mg/ml ; 0.000673 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.

-5.95 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

1.0 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)

1.3

Application In Synthesis of [ 367-24-8 ]

* 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 [ 367-24-8 ]

[ 367-24-8 ] Synthesis Path-Downstream   1~12

  • 1
  • [ 28563-38-4 ]
  • [ 367-24-8 ]
  • [ 51618-30-5 ]
  • 2
  • [ 367-24-8 ]
  • [ 140-89-6 ]
  • [ 51618-30-5 ]
  • 3
  • [ 367-24-8 ]
  • [ 883500-73-0 ]
  • 4
  • [ 755039-55-5 ]
  • [ 367-24-8 ]
  • [ 1021853-59-7 ]
YieldReaction ConditionsOperation in experiment
20% Stage 1 - (7R)-2-[(4-Bromo-2-fluorophenyl)amino]-8-cyclopentyl-7-ethyl-5-methyl-7,8- dihydropteridin-6(5H)-oneTo a suspension of 4-bromo-2-fluoro-phenylamine (388mg, 2.04mmol) in ethanol (2.5ml) and water (10ml) was added concentrated HCI (0.26ml) and intermediate A (300mg, 1.02mmol). The mixture was heated at 800C for 18 hours, cooled and the solvent was removed under reduced pressure. The residue was diluted with EtOAc (10ml) and washed with saturated NaHCO3 (2 x 10 ml). The organic layer was dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by column chromatography (20 - 50% EtOAc in heptane) to afford the title product as a yellow oil (90mg, 20%). ESMS: m/z 448, 449, 450 [Br splitting].
  • 5
  • [ 116247-92-8 ]
  • [ 367-24-8 ]
  • [ 1025392-81-7 ]
YieldReaction ConditionsOperation in experiment
A. (4-Bromo-2-fluoro-phenyl)-(l-pyrimidin-2-yl-piperidin-4-yl)-amine: To the mixture of bromoaniline (285 mg, 1.5 mmol) and ketone (266 mg, 1.5 mmol) in MeOH/AcOH (10:1, 5 ml) was added BH3-Py in THF (8M, 188 mul). The mixture was stirred at rt for 2h. The reaction mixture was concentrated and to the residue was added HCl (10%, 10 ml). The resulting mixture was stirred at rt for 30 min., then with cooling, the mixture was adjusted to alkaline with solid Na2CO3 and water. The aq. layer was extracted with EtOAc (5x 30 ml). The EtOAc was dried (Na2SO4) and concentrated. The residue was subjected to ISCO to give the titled compound as a white solid (230 mg).
  • 6
  • [ 367-24-8 ]
  • [ 57002-01-4 ]
  • [ 1400654-22-9 ]
YieldReaction ConditionsOperation in experiment
2.58 g With [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride; potassium tert-butylate; In isopropyl alcohol; at 20℃; for 15h;Inert atmosphere; (1) Isopropanol (60 mL) was added to PEPPSI-IPr catalyst (161 mg, 0.24 mmol) and tert-butoxy potassium (2.65 g, 23.6 mmol) under an argon atmosphere, and the mixture was stirred at room temperature for 15 min. To the reaction mixture were added <strong>[57002-01-4]trans-(2-cyclohexylvinyl)boronic acid</strong> (2.00 g, 13.0 mmol) and 4-bromo-2-fluoroaniline (2.24 g, 11.8 mmol) successively and the mixture was stirred at room temperature for 15 hr. Water was added thereto, the mixture was extracted with ethyl acetate, and the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The desiccant was filtered off and the filtrate was concentrated under reduced pressure to afford 4-[(E)-2-cyclohexylethenyl]-2-fluoroaniline as a reddish brown oil (2.58 g).
  • 7
  • [ 98556-31-1 ]
  • [ 367-24-8 ]
  • N-(4-bromo-2-fluorophenyl)-6-iodoquinazolin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% In isopropyl alcohol; at 20 - 80℃; for 2h; General procedure: To a solution of compound 9 (5.8 g, 20 mmol) in 2-propanol was added anilines (22 mmol) at room temperature (r.t.). Then the reaction mixture was heated to 80 C for 2 hours. After the start material was completed, the mixture was filtered through celite, and the cake was washed by 2-propanol, then dried to obtain the desired compounds 10a-10d. N-(4-Bromo-2-fluorophenyl)-6-iodoquinazolin-4-amine (10a): Yield 96%; mp 240-242C; 1H NMR (400MHz, DMSO-d6): δ 12.02 (s, 1H), 9.35 (d, 1H, J=1.5Hz), 8.94 (s, 1H), 8.40 (dd, 1H, J=8.8, 1.6Hz), 7.84-7.76 (m, 2H), 7.61-7.50 (m, 2H).
  • 8
  • [ 367-24-8 ]
  • [ 21080-80-8 ]
  • [ 2043-61-0 ]
  • 1-(4-bromo-2-fluorophenyl)-5-cyclohexyl-4-(cyclopropanecarbonyl)-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one [ No CAS ]
  • 9
  • [ 3132-99-8 ]
  • [ 367-24-8 ]
  • [ 21080-80-8 ]
  • 1-(4-bromo-2-fluorophenyl)-5-(3-bromophenyl)-4-(cyclopropanecarbonyl)-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one [ No CAS ]
  • 10
  • [ 367-24-8 ]
  • [ 337915-79-4 ]
  • 11
  • [ 367-24-8 ]
  • [ 216019-28-2 ]
  • C15H16FN [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.77 g With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene;Inert atmosphere; Reflux; Toluene (9 mL), ethanol (6 mL) and water (3 mL) were added into the mixture of M3(0.95 g, 5 mmoi), 3Methyiboronic acid (0.82 g, 5 mmoi) and potassium carbonate (1.73g, 12.5 mmol), stirred with nitrogen replacement for three times. Additional replacementwith nitrogen was performed for three times after 0.3 g of tetraphenylphenylphosphinepalladium was added. Then the reaction was warmed up for reflux reaction overnight.The product was filtered and concentrated, then 20 mL of dichloromethane and 10 mL ofwater were added and stilTed for 10 mitt The liquid was separated and washed with 10mL of water twice, dried with anhydrous sodium sulfate, filtered, concentrated andpurified by column chromatography. 0.77 g of M8 was achieved.
  • 12
  • [ 367-24-8 ]
  • [ 216019-28-2 ]
  • 2-((3-fluoro-3'-isopropyl-[1,1'-biphenyl]-4-yl)carbamoyl)cyclopent-1-ene-1-carboxylic acid [ No CAS ]
 

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