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Chemical Structure| 4488-40-8 Chemical Structure| 4488-40-8
Chemical Structure| 4488-40-8

4-Methyl-1-naphthoic acid

CAS No.: 4488-40-8

4.5 *For Research Use Only !

Cat. No.: A209848 Purity: 97%

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Product Details of [ 4488-40-8 ]

CAS No. :4488-40-8
Formula : C12H10O2
M.W : 186.21
SMILES Code : C1=CC=CC2=C(C=CC(=C12)C(O)=O)C
MDL No. :MFCD00671557
InChI Key :SIVYRLBDAPKADZ-UHFFFAOYSA-N
Pubchem ID :3014285

Safety of [ 4488-40-8 ]

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

Calculated chemistry of [ 4488-40-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 10
Fraction Csp3 0.08
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 55.87
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.

1.32
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

3.46
Log Po/w (WLOGP)?

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

2.85
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.

2.92
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

2.82
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.67

Water Solubility

Log S (ESOL):?

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

-3.64
Solubility 0.043 mg/ml ; 0.000231 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.

-3.92
Solubility 0.0221 mg/ml ; 0.000119 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

-3.83
Solubility 0.0272 mg/ml ; 0.000146 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.

-4.98 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

1.0
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)

1.0

Application In Synthesis of [ 4488-40-8 ]

* 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 [ 4488-40-8 ]

[ 4488-40-8 ] Synthesis Path-Downstream   1~30

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YieldReaction ConditionsOperation in experiment
With thionyl chloride; for 0.25h;Heating / reflux; To a stirred solution of 0.080 g (0.50 mmol) of 1-propylindole in 1.5 mL of dry CH2Cl2 at 0 C. under N2 was added dropwise 0.75 mL (0.75 mmol) of Me2AlCl (1 M in hexanes). The solution was stirred at 0 C. for 30 min and a solution of 0.122 g (0.6 mmol) of freshly prepared 4-methyl-1-naphthoyl chloride in 1.5 mL of CH2Cl2. The acid chloride was prepared form 0.122 g (0.60 mmol) of 4-methyl-1-naphthoic acid to which was added dropwise 1 mL of thionyl chloride at a rate sufficient to maintain a steady evolution of gas. This solution was heated at reflux for 15 min, cooled to ambient temperature and the excess thionyl chloride was removed in vacuo to give the acid chloride which was used without further purification. The deep red acylation reaction mixture was stirred at 0 C. until the reaction was complete as indicated by tlc (approximately 1 h). The reaction mixture was poured carefully into iced 1 M aqueous HCl and extracted with three portions of CH2Cl2. The combined extracts were washed wth three portions of aqueous NaHCO3, dried (MgSO4) and the solvent was removed in vacuo to give the crude product. After chromatography (petroleum ether:ethyl acetate, 9: 1) there was obtained 0.140 g (86%) of indole 41 as a white solid. Recrystallization from hexanes/ethyl acetate gave the analytical sample: m.p. 207-208 C.; 1H NMR (300 MHz, CDCl3) delta 0.90 (t, J=7.3 Hz, 3H), 1.81-1.88 (m, 2H), 2.78 (s, 3H), 4.03 (t, J=7.0 Hz, 2H), 7.37-7.38 (m, 5H), 7.48-7.59 (m, 3H), 8.09 (d, J=8.2 Hz, 1H), 8.27 (d, J=8.2 Hz, 1H), 8.52-8.54 (m, 1H); 13C NMR (75.5 MHz, CDCl3) delta 11.3, 19.7, 23.1, 48.7, 109.9, 117.6, 122.7, 122.9, 123.5, 124.2, 125.5, 125.8, 126.1, 126.3, 126.6, 127.0, 130.9, 132.8, 136.6, 137.0, 137.5, 137.9, 192.2; Anal. Calcd for C23H21NO: C, 84.37; H, 6.46; N, 4.28; Found: C, 84.25; H, 6.46; N, 4.30.
With thionyl chloride; In dichloromethane; for 4h;Reflux; Inert atmosphere; 4-Methyl-l-napthoyl chloride[0151] To a solution of 0.35 g (1.89 mmol) of 4-methyl-l-napthoic acid in 3 mL of dry dichloromethane under argon, was added 2.5 ml (34.3 mmol) of thionyl chloride. The solution was refluxed for 4 hrs and the solvent and excess thionyl chloride were removed by vacuum distillation to give a red oil, which was used without further purification.
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 2h; Step B: 4-Methylnaphthalenecarbonyl chloride.; Step B: 4-Methylnaphthalenecarbonyl chloride. Oxalyl chloride (0.53 niL, 6.1 mmol), followed by anhydrous DMF (2-3 drops) was added to a stirred solution of 4-methylnaphthalenecarboxylic acid (0.227 g, 1.22 mmol) in CH2Cl2 (10 mL). The mixture was stirred at room temperature for 2 h, evaporated and dried under vacuum for 0.5 h. to give the title acid chloride , which was used without further purification in step A.
With thionyl chloride; Step B. 2-(4-Methyl-l-naphthalenyl)-4H-pyrido [3,2-d] [1,3]oxazin-4-one; Following the procedure for Step B in Example 1, a suspension of 3-amino-2- pyridinecarboxylic acid (414 mg, 3.0 mmol) in CH2Cl2 (10 mL) and DIPEA (1.25 mL, 7.2 mmol) was treated with 4-methyl-l-naphthalenecarbonyl chloride, prepared from 4- methyl-1-naphthalenecarbonylic acid (590 mg, 3.17 mmol) with thionyl chloride (4.11 g, 35 mmol), and then with HATU (1.25 g, 3.3 mmol) in DMF (10 mL). The title compound was formed and directly used in Step A.

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  • [ 126558-73-4 ]
  • 10,11-Dioxa-tricyclo[6.4.2.02,7]tetradeca-1(13),2,4,6,8(14)-pentaene [ No CAS ]
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  • 4-Methyl-naphthalene-1-carbaldehyde oxime [ No CAS ]
  • [ 4488-40-8 ]
  • 1-Dinitromethyl-4-methyl-naphthalene [ No CAS ]
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  • [ 908093-98-1 ]
  • 4-Methyl-naphthalene-1-carboxylic acid benzhydryl ester [ No CAS ]
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  • 1-<4-methyl-naphthyl-(1)>-ethanone-(1) [ No CAS ]
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  • [ 15719-64-9 ]
  • <4-methyl-naphthyl-(1)>-magnesium bromide [ No CAS ]
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  • 29
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  • permanganate [ No CAS ]
  • diluted NaOH-solution [ No CAS ]
  • [ 605-70-9 ]
 

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