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Structure of 112204-58-7

Chemical Structure| 112204-58-7

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Product Details of [ 112204-58-7 ]

CAS No. :112204-58-7
Formula : C6H4BrFO
M.W : 191.00
SMILES Code : OC1=CC(Br)=CC=C1F
MDL No. :MFCD07782066
InChI Key :YPTHSYKJDRMAJY-UHFFFAOYSA-N
Pubchem ID :183421

Safety of [ 112204-58-7 ]

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

Computational Chemistry of [ 112204-58-7 ] 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 2.0
Num. H-bond donors 1.0
Molar Refractivity 36.12
TPSA ?

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

20.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.85
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

2.36
Log Po/w (WLOGP)?

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

2.71
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

2.48
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.42

Water Solubility

Log S (ESOL):?

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

-3.0
Solubility 0.189 mg/ml ; 0.00099 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.

-2.43
Solubility 0.718 mg/ml ; 0.00376 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

-2.96
Solubility 0.211 mg/ml ; 0.00111 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.

-5.79 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)

1.47

Application In Synthesis of [ 112204-58-7 ]

* 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.

  • Downstream synthetic route of [ 112204-58-7 ]

[ 112204-58-7 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 103291-07-2 ]
  • [ 112204-58-7 ]
YieldReaction ConditionsOperation in experiment
86% With boron tribromide; In dichloromethane; at 20℃; To a stirred solution OF 4-BROMO-1-FLUORO-2-METHOXYBENZENE (1.00 g, 4.88 mmol) in anhydrous CH2CL2 (20 ml) was added dropwise in an ice bath BBR3 (1 M solution in CH2Cl2, 9.75 ml, 9. 75 mmol), and the mixture was stirred at room temperature overnight. The reaction was cooled in an ice bath and quenched by adding MEOH (1.0 ml) dropwise. The solvent was evaporated and the residue purified by flash chromatography eluting with ISOHEXANE/CH2CL2/MEOH (70: 20: 10) to leave 0.802 g (86%) of the title compound: BH (400 MHz, CDCL3) 5.24 (1 H, s), 6.96 (2 H, m), 7.16 (1 H, DD, J7. 7,2. 0 HZ).
  • 2
  • [ 112204-58-7 ]
  • [ 74-88-4 ]
  • [ 103291-07-2 ]
YieldReaction ConditionsOperation in experiment
100% With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 65h; Reference Example-13 Potassium carbonate (18.8 g, 136 mmol) and methyl iodide (19.3 g, 136 mmol) were added to a solution of 5-bromo-2-fluorophenol (13.0 g, 68.1 mmol) in DMF (120 mL), followed by stirring at room temperature for 65 hours. After the reaction was completed, water (150 mL) was added to the reaction solution, and the resultant product was extracted with ethyl acetate (100 mL*1, 50 mL*2). The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure, whereby a pale yellow oily crude product (29.0 g) was obtained. This was purified by silica gel column chromatography (hexane:ethyl acetate=10:1), whereby 5-bromo-2-fluoroanisole (14.2 g, yield: quantitative) was obtained as a colorless oily material. 1H-NMR (400 MHz, CDCl3): delta3.88 (s, 3H), 6.95 (dd, J=8.6 and 10.8 Hz, 1H), 7.02 (ddd, J=2.2, 4.2 and 8.6 Hz, 1H), 7.08 (dd, J=2.2 and 7.6 Hz, 1H). 19F-NMR (376 MHz, CDCl3): delta-137 (s, 1F).
77% With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 40℃; for 2h; 100204] To a solution of 23 A (3.3 g, 17.3 mmol) and K2CO3 (4.78 g, 34.6 mmol) in DMF (20 mL) was added methyl iodide (1.46 niL, 23.4 mmol) at rt. The mixture was heated at 400C for 2.0 h. After cooling to rt, it was diluted with diethyl ether, washed with water and brine, dried over MgS O4. The crude residue was purified by flash column chromatography (EtOAc:hexanes = 1 : 6) to give 2.74 g(77%) of 23B as a viscous oil. 1H NMR (400 MHz, CDCl3) delta ppm 3.89 (s, 3 H), 6.95 - 7.00 (m, 3 H).
77% With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 40℃; To a solution of 7A (3.3 g, 17.3 mmol) and K2CO3 (4.78 g, 34.6 mmol) in DMF (20 mL) was added methyl iodide (1.46 mL, 23.4 mmol) at rt. The mixture was heated at 40 C. for 2.0 h. After cooling to rt, it was diluted with diethyl ether, washed with water and brine, dried over MgSO4. The crude residue was purified by flash column chromatography (EtOAc:hexanes=1:6) to give 2.74 g (77%) of 7B as a viscous oil. 1H NMR (400 MHz, CDCl3) delta ppm 3.89 (s, 3H), 6.95-7.00 (m, 3H).
77% With potassium carbonate; In N,N-dimethyl-formamide; at 40℃; for 2h; To a solution of 64A (3.3 g, 17.3 mmol) and K2CO3 (4.78 g, 34.6 mmol) in DMF (20 mL) was added methyl iodide (1.46 mL, 23.4 mmol) at rt. The mixture was heated at 40 C. for 2.0 h. After cooled to rt, it-was diluted with ether, washed with water and brine, dried over MgSO4. The crude residue was purified by flash column chromatography (EtOAc:hexanes=1:6) to give 2.74 g (77%) of 69A as viscous oil. 1H NMR (400 MHz, CDCl3) delta ppm 3.89 (s, 3 H), 6.95-7.00 (m, 3 H).

  • 3
  • [ 19047-31-5 ]
  • [ 112204-58-7 ]
  • [ 1595291-40-9 ]
YieldReaction ConditionsOperation in experiment
55.3% With potassium carbonate; In acetone; at 60℃; for 16h; A solution of <strong>[19047-31-5]2-chloro-N-cyclopropylacetamide</strong> (1.0 g, 7.5 mmol), 5-bromo-2- fluorophenol (1.44 g, 7.5 mmol) and K2C03 (1.55 g, 11.25 mmol) in 30 mL of acetone was heated at 60 C for 16 h. The mixture was filtered and concentrated to give a residue, which was purified by column chromatography (PE/EA, 2/1) to give the title as a yellow solid (1.2 g, 55.3 %). m/e 288 (M+H)+.
55.3% With potassium carbonate; In acetone; at 60℃; for 16h; Example 96 2-(5-Bromo-2-fluorophenoxy)-N-cyclopropylacetamide A solution of <strong>[19047-31-5]2-chloro-N-cyclopropylacetamide</strong> (1.0 g, 7.5 mmol), 5-bromo-2- fluorophenol (1.44 g, 7.5 mmol) and K2C03 (1.55 g, 11.25 mmol) in 30 mL of acetone was heated at 60 C for 16 h. The mixture was filtered and concentrated to give a residue, which was purified by column chromatography (PE/EA, 2/1) to give the title as a yellow solid (1.2 g, 55.3 %). m/e 288 (M+H)+.
  • 4
  • [ 2895-21-8 ]
  • [ 112204-58-7 ]
  • 2-(5-bromo-2-fluorophenoxy)-N-isopropylacetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% With potassium carbonate; In acetonitrile; at 70℃; for 16h; [0481] To the mixture of 5-bromo-2-fluoro-phenol (600.00 mg, 3.14 mmol), 2-chloro-N- lsopropylacetamide (510.90 mg, 3.77 mmol) in MeCN (15.00 mL) was added K2C03 (867.96 mg, 6.28 mmol). The mixture was stirred at 70 C for 16 h. LCMS showed one main peak of desired product. The reaction mixture was diluted with water (40 mL) and the mixture was extracted with EtOAc (40 mLx3). The combined organic layers were dried over Na2S04, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Si02, petroleum ether/EtOAc=l :0 to 4: 1) to give the title compound (900.00 mg, 98%) as light yellow solid. 1H NMR (400 MHz, DMSO-i/6) delta 7.97 (d, J= 7.2 Hz, 1H), 7.25- 7.20 (m, 2H), 7.17-7.16 (m, 1H), 4.58 (s, 2H), 3.95-3.87 (m, 1H), 1.08 (d, J= 6.8 Hz, 6H).
 

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