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Chemical Structure| 2150-47-2 Chemical Structure| 2150-47-2

Structure of Methyl 2,4-dihydroxybenzoate
CAS No.: 2150-47-2

Chemical Structure| 2150-47-2

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Product Details of [ 2150-47-2 ]

CAS No. :2150-47-2
Formula : C8H8O4
M.W : 168.15
SMILES Code : C1=C(C(=CC(=C1)O)O)C(OC)=O
MDL No. :MFCD00002276
InChI Key :IIFCLXHRIYTHPV-UHFFFAOYSA-N
Pubchem ID :16523

Safety of [ 2150-47-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335-H412
Precautionary Statements:P261-P273-P305+P351+P338

Computational Chemistry of [ 2150-47-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 41.77
TPSA ?

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

66.76 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.45
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

1.96
Log Po/w (WLOGP)?

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

0.88
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.

0.74
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

0.73
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.15

Water Solubility

Log S (ESOL):?

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

-2.36
Solubility 0.742 mg/ml ; 0.00441 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.

-2.99
Solubility 0.173 mg/ml ; 0.00103 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

-1.32
Solubility 8.1 mg/ml ; 0.0482 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

No
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.

-5.93 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.

0.55

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)

1.37

Application In Synthesis of [ 2150-47-2 ]

* 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.

  • Upstream synthesis route of [ 2150-47-2 ]
  • Downstream synthetic route of [ 2150-47-2 ]

[ 2150-47-2 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 2150-47-2 ]
  • [ 75-26-3 ]
  • [ 943519-37-7 ]
YieldReaction ConditionsOperation in experiment
45% With aluminum (III) chloride In dichloromethane at 50℃; for 24 h; Inert atmosphere A mixture of compound 6 (3.9g, 23.0mmol), 2-bromopropane (4.3mL, 46.0mmol), and aluminum chloride (6.1g, 46.0mmol) in CH2Cl2 was stirred at 50°C for 24h, equipped with a refluxing condenser under argon. 2-Bromopropane (4.3mL, 46.0mmol) was added to the reaction mixture three times every 6h. The mixture was neutralized with 10percent NaOH to pH 5, concentrated under reduced pressure, and then extracted with ethyl aceatate. The organic layer was washed with saturated NaHCO3 solution three times, dried over Na2SO4, concentrated under reduced pressure, and purified by column to afford compound 16 in 45percent yield. Rf=0.21 (1:4 ethyl acetate: hexane). 1H NMR (400MHz, CDCl3) δ 10.8 (s, 1H), 7.64 (s, 1H), 6.34 (s, 1H), 5.50 (s, 1H), 3.90 (s, 3H), 3.15–3.08 (m, 1H), 1.25 (d, J=10.8Hz, 6H). 13C NMR (100MHz, CDCl3) δ 170.7, 161.6, 159.6, 128.1, 127.1, 105.7, 103.2, 52.2, 26.7, 22.8.
45% With aluminum (III) chloride In dichloromethane at 50℃; for 24 h; Inert atmosphere Compound 7 was synthesized in the same manner as in Reaction Scheme 1 above.Compound 6 (3.9 g, 23.0 mmol), 2-bromopropane (4.3 mL, 46.0 mmol) and aluminum chloride (6.1 g, 46.0 mmol) were added in CH2Cl2 and stirred in a reflux condenser at 50 C for 24 hours under argon.2-Bromopropane (4.3 mL, 46.0 mmol) was added to the reaction mixture three times every 6 hours. The mixture was then neutralized by the addition of 10percent NaOH (pH 5), concentrated under reduced pressure and extracted with ethyl acetate.The organic layer was washed three times with saturated NaHCO3 solution, dried over Na2SO4 and concentrated under reduced pressure. The concentrate was then purified by silica gel chromatography to give compound 7 in 45percent yield.
45% With aluminum (III) chloride In dichloromethane at 50℃; for 30 h; Methylene chloride (CH2Cl2), the compound 4 (3.9 g, 23.0 mmol), 2-bromopropane (4.3 mL, 46.00 mmol) and aluminum chloride (6.1 g, , 46.0 mmol) were added and stirred at 50 ° C for 24 hours. 4.3 mL (46.0 mmol) of 2-bromopropane was then added to the reaction mixture three times for a total of 6 hours. The mixture was neutralized with 10percent sodium hydroxide until the pH reached 5, concentrated in a reduced pressure environment and extracted with ethyl acetate. The organic layer was washed three times with saturated NaHCO3 solution, dried in the presence of Na2SO4 and concentrated again under reduced pressure. It was then purified on a silica gel column to give compound 5 with a yield of 45percent. Rf = 0.21 (1: 4 ethyl acetate: hexane).
45% With aluminum (III) chloride In dichloromethane at 50℃; for 24 h; Inert atmosphere; Microwave irradiation 21.
Methyl 2,4-dihydroxy-5-isopropylbenzoate (12)
Compound 6 (3.9 g, 23.0 mmol), 2-bromopropane (4.3 mL, 46.0 mmol) and aluminum chloride (6.1 g, 46.0 mmol) were dissolved in CH2Cl2 and then stirred under argon at 50° C. for 24 hours with a reflux condenser under a microwave irradiation (Biotage Initiator).
3-Bromopropane (4.3 ml, 46.0 mmol) was added to the reaction mixture three times every 6 hours.
The mixture was neutralized with 10percent NaOH to pH 5, concentrated under pressure and extracted with ethyl acetate.
The organic layer was washed with saturated NaHCO3 solution three times, dried over Na2SO4, concentrated under pressure and purified by column to obtain Compound 12 in a yield of 45percent.
Rf=0.21 (1:4 ethyl acetate:hexane).
1H NMR (400 MHz, CDCl3) δ 10.8 (s, 1H), 7.64 (s, 1H), 6.34 (s, 1H), 5.53 (s, 1H), 3.92 (s, 3H), 3.15-3.08 (m, 1H), 1.25 (d, J=10.8 Hz, 6H).
13C NMR (100 MHz, CDCl3) δ 170.7, 161.6, 159.6, 128.1, 127.1, 105.7, 103.2, 52.2, 26.7, 22.8

References: [1] European Journal of Medicinal Chemistry, 2016, vol. 124, p. 1069 - 1080.
[2] Patent: KR101641829, 2016, B1, . Location in patent: Paragraph 0043-0044; 0051-0055.
[3] Patent: KR101789269, 2017, B1, . Location in patent: Paragraph 0046; 0048; 0054; 0055.
[4] Patent: US2019/31620, 2019, A1, . Location in patent: Paragraph 0190; 0191; 0192; 0193; 0194; 0290; 0291; 0292.
[5] European Journal of Medicinal Chemistry, 2018, vol. 143, p. 390 - 401.
 

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