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Chemical Structure| 18299-15-5 Chemical Structure| 18299-15-5

Structure of 18299-15-5

Chemical Structure| 18299-15-5

4-(Hydroxymethyl)-2-methylphenol

CAS No.: 18299-15-5

4.5 *For Research Use Only !

Cat. No.: A183345 Purity: 97%

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Product Details of [ 18299-15-5 ]

CAS No. :18299-15-5
Formula : C8H10O2
M.W : 138.16
SMILES Code : OC1=CC=C(CO)C=C1C
MDL No. :MFCD00238619
InChI Key :HSKGHUJMBLYPDO-UHFFFAOYSA-N
Pubchem ID :14251856

Safety of [ 18299-15-5 ]

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

Computational Chemistry of [ 18299-15-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 39.56
TPSA ?

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

40.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.71
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

1.05
Log Po/w (WLOGP)?

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

1.04
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.

1.21
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

1.65
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.33

Water Solubility

Log S (ESOL):?

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

-1.74
Solubility 2.54 mg/ml ; 0.0184 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.49
Solubility 4.47 mg/ml ; 0.0323 mol/l
Class?

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

Very 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

-2.01
Solubility 1.35 mg/ml ; 0.00977 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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.4 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)

1.0

Application In Synthesis of [ 18299-15-5 ]

* 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 [ 18299-15-5 ]

[ 18299-15-5 ] Synthesis Path-Downstream   1~31

  • 2
  • [ 50-00-0 ]
  • [ 95-48-7 ]
  • diluted NaOH-solution [ No CAS ]
  • [ 18299-15-5 ]
  • 3
  • [ 56-23-5 ]
  • [ 50-00-0 ]
  • [ 7732-18-5 ]
  • [ 95-48-7 ]
  • [ 22470-99-1 ]
  • [ 18299-15-5 ]
  • [ 7451-94-7 ]
  • [ 6641-13-0 ]
  • 5
  • [ 18299-15-5 ]
  • [ 105-36-2 ]
  • [ 637352-50-2 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; In acetonitrile; at 5℃; for 3h; To a solution [OF 4- (HYDROXYMETHYL)-2-METHYLPHENOL] (7.95 [G,] 57 [MMOL)] in dry acetonitrile (300 [ML)] at [5C,] was added cesium carbonate (20.42 g, 62 [MMOL)] and ethyl bromoacetate (6.38 mL, 57 [MMOL).] The resultant mixture was stirred for 3 h at [5C] under nitrogen. The reaction mixture was diluted with water (500 mL), extracted with EtOAc (2 x 750 mL), dried (Na2SO4) and the solvents removed in vacuo to afford the title compound as a yellow oil (12.3 g). ['H] NMR [(400MHZ] ; CDCI3) [5] : 1.3 (3H, t, J 7Hz), 2.3 [(3H,] [S),] 4.26 (2H, q, J [7HZ),] 4.59 (2H, s), 4.64 [(2H,] s), 6.68 (1H, d, J 8.5Hz), 7.12 (1H, dd, J 8.5Hz, 1. [5HZ),] 7.18 (1H, d, J 1. [5HZ),] OH not observed.
  • 6
  • [ 15174-69-3 ]
  • [ 18299-15-5 ]
YieldReaction ConditionsOperation in experiment
To a solution [OF 4-HYDROXY-3-METHYLBENZALDEHYDE (10G,] 73.5 [MMOL)] in dry [CH2CI2] (550 mL) under nitrogen at [5C] was added tetra-N-butylammonium borohydride (20.58 g, 80 [MMOL)] and the resultant mixture stirred for 1.25 h at [5C.] Saturated ammonium chloride solution (30 mL) was added to the reaction mixture and the resultant mixture stirred for 1 h at [5C.] Saturated ammonium chloride solution (60 mL) was added and the reaction mixture extracted with [CH2CI2,] dried [(NA2SO4)] and the solvents removed in vacuo. Purification by flushing through silica (2 x 150 g) eluting with EtOAc afforded the title compound as an oily yellow solid (8.01 g). [1H] NMR (400 MHz; [MEOH-D4)] 8 : 2.19 (3H, s), 4.46 (2H, s), 6.71 [(1H, D,] J 8Hz), 6.99 [(1H,] dd, J 8Hz, 2Hz), 7.06 (1 H, d, J 2Hz), OH not observed.
  • 7
  • [ 79-46-9 ]
  • [ 18299-15-5 ]
  • 1,1-dimethyl-2-(4-methoxy-3-methylphenyl)ethylamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tetrabutyl ammonium fluoride; EXAMPLE 68: Preparation of N-(2-Hydroxy-3-phenoxypropyl)-1,1-dimethyl-2-(4-methoxy-3-methylphenyl) ethylamine Hydrochloride, Compound 117 STR68 Using the method of Example 64, supra, 4-hydroxy-3-methylbenzyl alcohol (1.0 g, 7.25 mmol), 2-nitropropane (5 mL), and tetrabutylammonium fluoride (0.38 g, 0.145 mmol) were used to prepare 0.8 g of 1,1-dimethyl-2-(4-methoxy-3-methylphenyl)ethylamine.
  • 8
  • [ 18299-15-5 ]
  • C11H16O2 [ No CAS ]
  • C19H24O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran;Inert atmosphere; Cooling with ice; Under a nitrogen atmosphere, a compound represented by formula (I-a 9 V 3), formula (I-a 9 c 4) compound represented, triphenylphosphine, tetrahydrofuran was added. Diisopropyl azodicarboxylate is added while stirring on ice. After the usual treatment, then purified by column chromatography, to give a compound of formula (I-a 9 d 5) expressed.
  • 9
  • [ 18299-15-5 ]
  • [ 439134-88-0 ]
  • 10
  • [ 18299-15-5 ]
  • (4-[butyl(2,4'-dimethyl-1,1'-biphenyl-3-yl)amino]methyl}-2-methylphenoxy)acetic acid [ No CAS ]
  • 11
  • [ 18299-15-5 ]
  • [4-({(2-methoxyethyl)[4'-(trifluoromethyl)-1,1'-biphenyl-3-yl]amino}methyl)-2-methylphenoxy]acetic acid [ No CAS ]
  • 12
  • [ 18299-15-5 ]
  • {2-methyl-4-[(2-propen-1-yl{6-[4-(trifluoromethyl)phenyl]pyridin-2-yl}amino)methyl]phenoxy}acetic acid [ No CAS ]
  • 13
  • [ 18299-15-5 ]
  • [2-methyl-4-([2-(methylthio)ethyl][4'-(trifluoromethyl)-1,1'-biphenyl-3-]amino}methyl)phenoxy]acetic acid [ No CAS ]
  • 14
  • [ 18299-15-5 ]
  • [2-methyl-4-({propyl[4'-(trifluoromethyl)-1,1'-biphenyl-3-yl]amino}methyl)phenoxy]acetic acid [ No CAS ]
  • 15
  • [ 18299-15-5 ]
  • [4-({butyl[4'-(trifluoromethyl)-1,1'-biphenyl-3-yl]amino}methyl)-2-methylphenoxy]acetic acid [ No CAS ]
  • 16
  • [ 18299-15-5 ]
  • [4-({(2-methoxyethyl)[2-methyl-4'-(trifluoromethyl)-1,1'-biphenyl-3-yl]amino}methyl)-2-methylphenoxy]acetic acid [ No CAS ]
  • 17
  • [ 18299-15-5 ]
  • [2-methyl-4-({pentyl[4'-(trifluoromethy)-1,1'-biphenyl-3-yl]amino}methyl)phenoxy]acetic acid [ No CAS ]
  • 18
  • [ 18299-15-5 ]
  • [4-({butyl[2-methyl-4'-(trifluoromethyl)-1,1'-biphenyl-3-yl]amino}methyl)-2-methylphenoxy]acetic acid [ No CAS ]
  • 19
  • [ 18299-15-5 ]
  • [4-({(2-cyclopropylethyl)[4'-(trifluoromethyl)-1,1'-biphenyl-3-yl]amino}methyl)-2-methylphenoxy]acetic acid [ No CAS ]
  • 20
  • [ 18299-15-5 ]
  • [ 637352-51-3 ]
  • 21
  • [ 18299-15-5 ]
  • [ 637352-94-4 ]
  • 22
  • [ 18299-15-5 ]
  • [ 637352-64-8 ]
  • 23
  • [ 18299-15-5 ]
  • [ 637353-08-3 ]
  • 24
  • [ 18299-15-5 ]
  • [ 637352-62-6 ]
  • 25
  • [ 18299-15-5 ]
  • [ 637352-59-1 ]
  • 26
  • [ 18299-15-5 ]
  • [ 637352-58-0 ]
  • 27
  • [ 18299-15-5 ]
  • [ 637352-60-4 ]
  • 28
  • [ 18299-15-5 ]
  • [ 637352-70-6 ]
  • 29
  • [ 18299-15-5 ]
  • [ 637352-61-5 ]
  • 30
  • [ 18299-15-5 ]
  • [ 637352-69-3 ]
  • 31
  • [ 698367-00-9 ]
  • [ 18299-15-5 ]
  • 5-[[4-(hydroxymethyl)-2-methylphenoxy]methyl]-3-methyl-1-phenyl-1H-pyrazole-4-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With caesium carbonate; at 80℃; for 4h; General procedure: A mixture of the chloride 4 (1.0 eq), the appropriate alcohol (1.0 eq), and K2CCh or Cs2C03 (2.0 eq) in acetonitrile or A, A- d i m c t h y 1 fo r m a m i d c was stirred for a time period between 2h and overnight at a temperature ranging between room temperature and the reflux temperature. After cooling to rt, H20 was added and the reaction mixture was extracted with EtOAc (x3). The combined organic layers were washed with brine, dried over Na2S04, filtered and evaporated under vacuum. The desired product was obtained after purification of the crude material as reported in the specific examples.
 

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