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Chemical Structure| 76283-09-5 Chemical Structure| 76283-09-5

Structure of 4-Bromo-2-fluorobenzyl bromide
CAS No.: 76283-09-5

Chemical Structure| 76283-09-5

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Product Details of [ 76283-09-5 ]

CAS No. :76283-09-5
Formula : C7H5Br2F
M.W : 267.92
SMILES Code : FC1=CC(Br)=CC=C1CBr
MDL No. :MFCD00055467
InChI Key :XMHNLZXYPAULDF-UHFFFAOYSA-N
Pubchem ID :2733660

Safety of [ 76283-09-5 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H314-H412
Precautionary Statements:P280-P301+P310-P305+P351+P338-P310
Class:8(6.1)
UN#:2923
Packing Group:

Computational Chemistry of [ 76283-09-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 46.94
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.49
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

3.27
Log Po/w (WLOGP)?

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

3.75
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.

4.25
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

3.93
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.54

Water Solubility

Log S (ESOL):?

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

-3.94
Solubility 0.0308 mg/ml ; 0.000115 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.

-2.94
Solubility 0.304 mg/ml ; 0.00114 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

-4.79
Solubility 0.00439 mg/ml ; 0.0000164 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

Low
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

Yes
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.

-5.61 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

1.0
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

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<0.0
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 [ 76283-09-5 ]

* 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 [ 76283-09-5 ]

[ 76283-09-5 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 521-73-3 ]
  • [ 76283-09-5 ]
  • [ 159029-74-0 ]
  • 2
  • [ 391-12-8 ]
  • [ 76283-09-5 ]
  • petrol [ No CAS ]
  • 1-(4-bromo-2-fluorobenzyl)-7-trifluoromethylindoline-2,3-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; chlorobenzene; The starting material was obtained as follows: Anhydrous potassium carbonate (10.7 g.) and 7-trifluoromethyl indoline-2,3-dione (14.4 g.) were stirred in N,N-dimethylformamide (DMF) (100 ml.) for 30 minutes. A portion (78.9 ml.) of a 25percent w/v solution of 4-bromo-2-fluorobenzyl bromide in chlorobenzene was then added and the mixture was stirred at 75°-78° C. for 2 hours. The mixture was then cooled to ambient temperature and poured into water (400 ml.). Petrol 60-80 (200 ml.) was added to the aqueous mixture and the whole was stirred for 30 minutes. The solid which formed was separated by filtration to give 1-(4-bromo-2-fluorobenzyl)-7-trifluoromethyl indoline-2,3-dione (17.8 g.), m.p. 141°-143° C.
  • 3
  • [ 76283-09-5 ]
  • [ 205383-87-5 ]
  • [ 1426689-05-5 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In acetonitrile; at 20℃; Tert-butyl 2-oxospiro[indoline-3,3?-pyrrolidine]-1?-carboxylate (1 g, 3.4 mmol) was added to a round bottom flask containing a stir bar and dissolved in acetonitrile (15 mL). Potassium carbonate (940 mg, 6.8 mmol) was added, followed by 4-bromo-1-(bromomethyl)-2-fluorobenzene (929 mg, 3.4 mmol). The mixture was stirred at room temperature overnight, and then evaporated under reduced pressure. The resulting residue was partitioned between water and ethyl acetate. The organic layer was collected, and the water layer was extracted with an additional ethyl acetate (2×50 mL). The organic layers were combined, dried over magnesium sulfate, and evaporated to afford a colorless solid, which was used directly in the next step. To a microwave vial containing a stir bar was added tert-butyl 1-(4-bromo-2-fluorobenzyl)-2-oxospiro[indoline-3,3?-pyrrolidine]-1?-carboxylate (457 mg, 0.96 mmol), followed by 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (200 mg, 0.96 mmol), cesium carbonate (626 mg, 1.9 mmol), 1,1?-bis(diphenylphosphino)ferrocene]-dichloropalladium (II) dichloromethane adduct (78 mg, 0.096 mmol), and the mixture was suspended in THF/water (4 mL, 1:1). The vial was sealed, and the mixture was heated to 160 C. for 10 min. The organic layer was removed, filtered through celite and evaporated to afford an oil, which was re-dissolved in excess TFA. This solution was allowed to stir at room temperature for 2 h, and then TFA was evaporated under reduced pressure. The resulting oil was used directly in the next step. 1-(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)spiro[indoline-3,3?-pyrrolidin]-2-one (75 mg, 0.2 mmol) was added to a vial containing a stir bar and dissolved in DMF (1 mL). Potassium carbonate (41 mg, 0.3 mmol) was added, followed by iodomethane (15 muL, 0.2 mmol). The vial was sealed, and the mixture was stirred at room temperature for 2 h. The suspension was filtered to remove solids, and then purified using an SCX cartridge to afford the title compound as a clear oil. LCMS: RT=0.59 min, >99% (at) 254 nm, >99% (at) 215 nm; m/z (M+1)+=391. 1H NMR (400 MHz, CDCl3, delta (ppm)): 7.7 (s, 1H), 7.6 (s, 1H), 7.5 (dd, J=7.4, 0.6 Hz, 1H), 7.3-7.1 (m, 4H), 7.1-7.0 (m, 1H), 6.8 (d, J=7.8 Hz, 1H), 5.0 (s, 2H), 4.0 (s, 3H), 3.1-3.0 (m, 1H), 3.0-2.9 (m, 2H), 2.8-2.7 (m, 1H), 2.5 (s, 3H), 2.5-2.4 (m, 1H), 2.1 (dt, J=12.8, 7.7 Hz, 1H), HRMS calculated for C23H24N4OF (M+H)+ m/z: 391.1934, measured: 391.1933.
  • 4
  • [ 76283-09-5 ]
  • [ 872422-15-6 ]
  • 5
  • [ 89942-77-8 ]
  • [ 76283-09-5 ]
  • C15H11BrFNO5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Compound 1 (10 mmol), anhydrous potassium carbonate (20 mmol, K2CO3) and DMF (20 mL) were added to a 100 mL-dry eggplant flask and stirred at room temperature for 30 min prior to addition of p-bromobenzyl bromide (12 mmol). The resulting mixture was maintained at 80 C for 3-8 h, and the reaction course was monitored using TLC. Upon the reaction completion, the mixture was cooled to room temperature before the addition of 100mL of water, and the system was extracted with ethyl acetate (30 mL 3). The organic phase was dried over anhydrous Na2SO4 and concentrated using rotary evaporator. The crude product 2 was used in the next step without further purification.
 

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