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Chemical Structure| 16650-55-8

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Product Details of [ 16650-55-8 ]

CAS No. :16650-55-8
Formula : C11H7BrO2
M.W : 251.08
SMILES Code : O=C(C1=C2C=CC=CC2=C(Br)C=C1)O
MDL No. :MFCD00094221
InChI Key :FIJIPZQZVLCOMB-UHFFFAOYSA-N
Pubchem ID :282591

Safety of [ 16650-55-8 ]

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

Computational Chemistry of [ 16650-55-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 58.61
TPSA ?

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

37.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.9
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

3.79
Log Po/w (WLOGP)?

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

3.3
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.

3.32
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

3.0
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.06

Water Solubility

Log S (ESOL):?

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

-4.25
Solubility 0.0142 mg/ml ; 0.0000566 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-4.27
Solubility 0.0136 mg/ml ; 0.000054 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

-4.3
Solubility 0.0125 mg/ml ; 0.0000497 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

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.

-5.14 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.

0.56

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)

1.21

Application In Synthesis of [ 16650-55-8 ]

* 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 [ 16650-55-8 ]

[ 16650-55-8 ] Synthesis Path-Downstream   1~9

  • 3
  • [ 16650-55-8 ]
  • [ 77-78-1 ]
  • [ 35615-97-5 ]
  • 4
  • [ 46258-62-2 ]
  • diluted aqueous nitric acid [ No CAS ]
  • [ 16650-55-8 ]
  • 6
  • [ 79-37-8 ]
  • [ 16650-55-8 ]
  • [ 35615-97-5 ]
YieldReaction ConditionsOperation in experiment
In methanol; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; N,N-dimethyl-formamide; (a) Methyl 4-bromo-1-naphthoate. A solution of 4-bromo-1-naphthoic acid (Fischer, A; et al, J. Chem. Soc., 1426 (1958)) oxalyl chloride (2.56 g), and DMF (5 muL) in DCM (100 mL) was stirred for 3 h, concentrated, then redissolved in DCM (5 mL). Methanol was added and stirring continued overnight. Following concentration and purification by chromatography (DCM) the product was afforded as a white solid (4.85 g). 1H NMR (DMSO-d6): delta 8.83-8.77 (m, 1H), 8.31-8.25 (m, 1 H), 8.01 (s, 1 H), 7.82-7.75 (m, 2H), 3.96 (s, 3 H); MS m/z 265 (M+H).
In methanol; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; N,N-dimethyl-formamide; (a) Methyl 4-bromo-1-naphthoate. A solution of 4-bromo-1-naphthoic acid (Fischer, A; et al, J. Chem. Soc., 1426 (1958)) oxalyl chloride (2.56 g), and DMF (5 muL) in DCM (100 mL) was stirred for 3 h, concentrated, then redissolved in DCM (5 mL). Methanol was added and stirring continued overnight. Following concentration and purification by chromatography (DCM) the product was afforded as a white solid (4.85 g). 1H NMR (DMSO-d6): delta 8.83-8.77 (m, 1H), 8.31-8.25 (m, 1 H), 8.01 (s, 1 H), 7.82-7.75 (m, 2H), 3.96 (s, 3 H); MS m/z 265 (M+H).
  • 7
  • [ 67-56-1 ]
  • [ 16650-55-8 ]
  • [ 35615-97-5 ]
YieldReaction ConditionsOperation in experiment
98% 4-bromo-naphthoic acid (4.0 g, 16.0 mmol) in a 250 mL three-necked flask, add 40 mL of S0C12, 5 drops of pyridine, and react at 85 C for 12 h. The excess was distilled off under reduced pressure The flask was cooled to room temperature. 60 mL of methanol was added to the flask. The reaction was heated at 85 C for 5 hours. The excess methanol was evaporated to give a pale yellow solid A (4.13 g) in 98% yield.
91% With sulfuric acid; for 18h;Reflux; Preparation 1: methyl 4-bromo-1-naphthoate To a solution of 4-bromo naphthoic acid (4.0 g, 15.9 mmol) in MeOH (75 mL) was added sulfuric acid (0.5 mL) and the reaction was heated to reflux for 18 hours. TLC 50:50 EtOAc:heptane showed consumption of starting material. The reaction was cooled and concentrated under vacuum to remove MeOH. The residue was diluted with EtOAc (150 mL), washed with water (100 mL), diluted with saturated NaHCO3 (100 mL), dried over Na2SO4 and concentrated under vacuum to afford a solid (3.85 g, 91%). 1H NMR (CDCl3) delta ppm: 8.96 (1H), 8.36 (1H), 8.02 (1H), 7.85 (1H), 7.70-7.66 (2H), 4.03 (3H).
0.55 g With sulfuric acid; for 3h;Reflux; General procedure: To a solution of 2.44 g (11.9 mmol) of 1-acetyl-4-chloronaphthalene in 5 mL of freshly distilled pyridine under N2 was added 3.33 g (13.1 mmol) of I2 dissolved in 15 mL of freshly distilled pyridine. The mixture was heated at reflux for 40 min, cooled to ambient temperature and diluted with ether until a brown precipitate formed. The precipitate was filtered off, suspended in 12 mL of 6 M aqueous NaOH and heated at reflux for 2 h. After cooling the solution was acidified with 10% HCl, the crude 4-chloro-1-naphthoic acid was extracted into ether and the ethereal extract was washed with brine. After drying (MgSO4) the solution was concentrated in vacuo. The product was dissolved in 25 mL of MeOH to which 5 mL of concentrated H2SO4 was cautiously added. The solution was heated at reflux for 3 h. After cooling to ambient temperature the crude ester was extracted into ether, the ethereal solution was washed with brine and dried (MgSO4). The solution was concentrated in vacuo to give 1.66 g (63%) of methyl 4-chloro-1-naphthoate as a brown oil, which was used without further purification
  • 8
  • [ 35615-97-5 ]
  • [ 16650-55-8 ]
YieldReaction ConditionsOperation in experiment
73% General procedure: To a solution of 2.44 g (11.9 mmol) of 1-acetyl-4-chloronaphthalene in 5 mL of freshly distilled pyridine under N2 was added 3.33 g (13.1 mmol) of I2 dissolved in 15 mL of freshly distilled pyridine. The mixture was heated at reflux for 40 min, cooled to ambient temperature and diluted with ether until a brown precipitate formed. The precipitate was filtered off, suspended in 12 mL of 6 M aqueous NaOH and heated at reflux for 2 h. After cooling the solution was acidified with 10% HCl, the crude 4-chloro-1-naphthoic acid was extracted into ether and the ethereal extract was washed with brine. After drying (MgSO4) the solution was concentrated in vacuo. The product was dissolved in 25 mL of MeOH to which 5 mL of concentrated H2SO4 was cautiously added. The solution was heated at reflux for 3 h. After cooling to ambient temperature the crude ester was extracted into ether, the ethereal solution was washed with brine and dried (MgSO4). The solution was concentrated in vacuo to give 1.66 g (63%) of methyl 4-chloro-1-naphthoate as a brown oil, which was used without further purification: 1H NMR (300 MHz, CDCl3) delta 3.90 (s, 3H), 7.38 (d, J = 7.8, 1H), 7.45-7.56 (m, 2H), 7.87 (d, J = 8.1, 1H), 8.18 (d, J = 8.4, 1H), 8.93 (d, J = 8.1, 1H); 13C NMR (75.5 MHz, CDCl3) delta 52.1, 124.6, 124.9, 125.8. 126.2, 127.1, 128.3, 129.9, 130.7, 132.3, 137.2, 166.9; GC/MS (EI) m/z (rel intensity) 220 (61), 189 (100), 161 (48), 126 (42).A mixture of 0.25 g (1.1 mmol) of methyl 4-chloro-1-naphthoate and 2.10 g (37.4 mmol) of KOH in 20 mL of H2O was heated at reflux for 12 h under N2. The reaction mixture was cooled to ambient temperature, acidified with concentrated HCl and the product was extracted into ether and dried (MgSO4). The organic phase was concentrated in vacuo to give 0.27 g (88%) of 4-chloro-1-naphthoic acid as an off-white solid
  • 9
  • [ 72287-26-4 ]
  • [ 16650-55-8 ]
  • potassium vinyltrifluoroborate [ No CAS ]
  • 4-vinyl-1-naphthoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; Example 37 Preparation of 4-vinyl-1-naphthoic acid (C179) To a stirred solution of 4-bromo-1-naphthoic acid (2.50 g, 9.98 mmol) in dimethyl sulfoxide (32.3 mL) was added potassium vinyltrifluoroborate (1.33 g, 9.96 mmol), potassium carbonate (3.85 g, 27.9 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (0.364 g, 0.498 mmol). The reaction mixture was heated in an 80° C. bath for 18 hours. The reaction mixture was cooled to ambient temperature and diluted with 1 N aqueous hydrochloric acid solution (150 mL) and water (150 mL). The mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (SiO2, eluting with 0-100percent ethyl acetate gradient in hexanes) to afford the title compound as a bright yellow solid (1.36 g, 62percent): mp 147-155° C.; 1H NMR (300 MHz, acetone-d6) delta 11.42 (s, 1H), 9.16-9.03 (m, 1H), 8.31-8.25 (m, 2H), 7.77 (dd, J=7.7, 0.7 Hz, 1H), 7.70-7.57 (m, 3H), 5.95 (dd, J=17.2, 1.5 Hz, 1H), 5.62 (dd, J=11.1, 1.5 Hz, 1H); ESIMS m/z 197.1 ([M-H]-).
 

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