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Chemical Structure| 14472-14-1 Chemical Structure| 14472-14-1

Structure of 14472-14-1

Chemical Structure| 14472-14-1

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Product Details of [ 14472-14-1 ]

CAS No. :14472-14-1
Formula : C7H7BrO
M.W : 187.03
SMILES Code : C1=C(C(=CC=C1O)Br)C
MDL No. :MFCD00079723
Boiling Point : No data available
InChI Key :GPOQODYGMUTOQL-UHFFFAOYSA-N
Pubchem ID :72857

Safety of [ 14472-14-1 ]

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

Computational Chemistry of [ 14472-14-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 41.13
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.

1.81
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

2.86
Log Po/w (WLOGP)?

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

2.46
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.

2.57
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

2.5
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.44

Water Solubility

Log S (ESOL):?

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

-3.29
Solubility 0.0949 mg/ml ; 0.000507 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 0.213 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

-3.06
Solubility 0.162 mg/ml ; 0.000865 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.

-5.41 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)

1.0

Application In Synthesis of [ 14472-14-1 ]

* 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 [ 14472-14-1 ]

[ 14472-14-1 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 14472-14-1 ]
  • [ 1013-83-8 ]
  • 5-bromo-[2]naphthoic acid-(4-bromo-3-methyl-phenyl ester) [ No CAS ]
  • 3
  • [ 14472-14-1 ]
  • [ 74204-00-5 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 3 The method is as in Example 1, but using 2.9 mmol of 3-methyl-4-bromophenol. After 48 hours of reaction at ambient temperature, 80percent of 3-methyl-5-bromophenol is formed.
YieldReaction ConditionsOperation in experiment
80% Example 24(e) 3-1H-Benzoimidazol-2-yl-6-(2-ethyl-4-hydroxyphenyl)-1H-indazole Example 24 (e) was prepared in a similar manner to that described for Example 24(a), except that 4-bromo-3-ethyl-phenol, prepared in 80% yield according to the procedure described by Carreno et. al., Syn. Lett., 11, 1241-42 (1997) for the synthesis of 4-bromo-3-methyl-phenol, was used instead of 4-bromo-2-methoxy-5-methyl-phenol in step (vi). 1H NMR (300 MHz, DMSO-d6) delta 13.66 (s, 1H), 13.02 (s, 1H), 9.43 (s, 1H), 8.49 (d, 1H, J=8.4 Hz), 7.72 (d, 1H, J=6.9 Hz), 7.53 (d, 1H, J=6.9 Hz), 7.44 (s, 1H), 7.18-7.25 (m, 3H), 7.06 (d, 1H, J=8.1 Hz), 6.75 (d, 1H, J=2.1 Hz), 6.66 (dd, 1H, J=8.1, 2.1 Hz), 2.50 (q, 2H, J=7.5 Hz), 1.04 (t, 3H, J=7.5 Hz). MS (ES) [m+H]/z calc'd 355, found 355; [m-H]/z calc'd 353, found 353.
  • 6
  • [ 74-96-4 ]
  • [ 14472-14-1 ]
  • [ 68155-69-1 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In acetonitrile; at 80℃; Example XVI.1 (general route) 1 -Bromo-4-cvclopropylmethoxybenzene 5.0 g (28.9 mmol) 4-bromophenol, 3.93 g (43.4 mmol) (chloromethyl)cyclopropane and 7.99 g (57.8 mmol) K2CO3 are added to 10 mL DMF and stirred at 80°C over night. Afterwards the reaction mixture is diluted with water and extracted with DCM. The organic layer is dried over MgSO4 and the solvent is removed in vacuo. CioHn BrO (M= 227.1 g/mol) EI-MS: 226/228 [M]+ Rt (HPLC): 1 .20 min (method C) The following compounds are prepared analogously to example XVI.1 For example XVI.2 and XVI.24 the reaction temperature is 120 °C. For the examples XVI.17-23 and XVI.3132ACN is used as solvent. The example XVI.30 can be prepared also by using Mitsunobu conditions (2,2- difluorocydopropylnnethanol, appropriate phenol, DIAD, TPP; THF, r.t. over night)
  • 7
  • [ 263400-88-0 ]
  • [ 14472-14-1 ]
  • 1-bromo-4-(3-methanesulfonylpropoxy)-2-methylbenzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 2h; (A) To a mixture of 4-bromo-3-methylphenol (1 g, 5.35 mmol) and K2CO3 (1.1 g, 7.96 mmol) in DMF (10 mL) was added <strong>[263400-88-0]3-(methylsulfonyl)propyl 4-methylbenzenesulfonate</strong> (1.72 g, 5.88 mmol) and the resultant mixture was stirred at 80 C for 2 h. After cooling to rt, satd. aq. NH4Cl (10 mL) was added and the resultant solution was extracted with EtOAc (3 x 20 mL). The combined organic extracts were concentrated under reduced pressure and the residue thus obtained was purified by silica gel chromatography (0-30% ethyl acetate/petroleum ether) to afford 1-bromo-4-(3-methanesulfonylpropoxy)-2- methylbenzene (1.5 g, 91 %) as a white solid. 1H NMR (CDCl3) 7.40 (d, J = 8.7 Hz, 1H), 6.78 (d, J = 2.7 Hz, 1H), 6.59 (dd, J = 3.0, 8.7 Hz, 1H), 4.06 - 4.16 (m, 2H), 3.24(t, J =7.8 Hz, 2H), 2.95 (s, 3H), 2.29 - 2.38(m, 5H).
91% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 2h; (A) To a mixture of 4-bromo-3-methylphenol (1 g, 5.35 mmol) and K2CO3 (1.1 g, 7.96 mmol) in DMF (10 mL) was added <strong>[263400-88-0]3-(methylsulfonyl)propyl 4-methylbenzenesulfonate</strong> (1.72 g, 5.88 mmol) and the resultant mixture was stirred at 80 C. for 2 h. After cooling to rt, satd. aq. NH4Cl (10 mL) was added and the resultant solution was extracted with EtOAc (3*20 mL). The combined organic extracts were concentrated under reduced pressure and the residue thus obtained was purified by silica gel chromatography (0-30% ethyl acetate/petroleum ether) to afford 1-bromo-4-(3-methanesulfonylpropoxy)-2-methylbenzene (1.5 g, 91%) as a white solid. 1H NMR (CDCl3) delta 7.40 (d, J=8.7 Hz, 1H), 6.78 (d, J=2.7 Hz, 1H), 6.59 (dd, J=3.0, 8.7 Hz, 1H), 4.06-4.16 (m, 2H), 3.24 (t, J=7.8 Hz, 2H), 2.95 (s, 3H), 2.29-2.38 (m, 5H).
  • 8
  • [ 14472-14-1 ]
  • [ 194152-05-1 ]
  • 4-(4-bromo-3-methylphenoxy)tetrahydro-2H-thiopyran 1,1-dioxide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With di-tert-butyl-diazodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 50℃;Inert atmosphere; General Procedure B: (0436) To a mixture of the alcohol (0.2 mmol) and the phenol (0.3 mmol) in dry THF (1 mL) was added a mixture of the phosphine (Ph3P, Bu3P or t-Bu3P; 0.3 mmol) and the azidodicarboxylate (DEAD, DIAD, DBAD or ADDP; 0.3 mmol), and the resultant solution was stirred under argon for 1-16 h. The mixture was then either worked up by an extractive process (ex., quenching with satd. aq. NH4Cl and extraction with EtOAc) or concentrated directly under reduced pressure and the resultant residue was purified by silica gel chromatography (EtOAc/heptanes) or EtOAc/petroleum ether to afford the desired phenolic ether. (A) 4-(4-Bromo-3-methylphenoxy)tetrahydro-2H-thiopyran 1,1-dioxide was prepared from 4-bromo-3-methylphenol and <strong>[194152-05-1]4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide</strong> following General Procedure B, using DBAD and Ph3P at a reaction temperature of 50° C. overnight. 1H NMR (CDCl3) delta 7.43 (d, J=8.7 Hz, 1H), 6.84 (d, J=3.0 Hz, 1H), 6.64 (dd, J=2.7, 8.7 Hz, 1H), 4.59-4.61 (m, 1H), 3.33-3.43 (m, 2H), 2.90-2.96 (m, 2H), 2.30-2.48 (m, 7H).
  • 9
  • [ 871836-51-0 ]
  • [ 14472-14-1 ]
  • C13H10BrN3O [ No CAS ]
  • 10
  • [ 14472-14-1 ]
  • [ 1186194-98-8 ]
  • C13H8BrClF3NO [ No CAS ]
 

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