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Chemical Structure| 99585-14-5 Chemical Structure| 99585-14-5
Chemical Structure| 99585-14-5

Methyl 2-chloro-6-methylbenzoate

CAS No.: 99585-14-5

4.5 *For Research Use Only !

Cat. No.: A164017 Purity: 95%

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Product Details of [ 99585-14-5 ]

CAS No. :99585-14-5
Formula : C9H9ClO2
M.W : 184.62
SMILES Code : O=C(OC)C1=C(C)C=CC=C1Cl
MDL No. :MFCD06204147
InChI Key :RYUYMMGUQYRLQX-UHFFFAOYSA-N
Pubchem ID :22935202

Safety of [ 99585-14-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Calculated chemistry of [ 99585-14-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 47.7
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.34
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

2.64
Log Po/w (WLOGP)?

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

2.44
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.

2.82
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

2.8
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.61

Water Solubility

Log S (ESOL):?

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

-2.89
Solubility 0.24 mg/ml ; 0.0013 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.

-2.84
Solubility 0.265 mg/ml ; 0.00144 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

-3.48
Solubility 0.0616 mg/ml ; 0.000333 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.

-5.55 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)

1.54

Application In Synthesis [ 99585-14-5 ]

* 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.

  • Upstream synthesis route of [ 99585-14-5 ]
  • Downstream synthetic route of [ 99585-14-5 ]

[ 99585-14-5 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 67-56-1 ]
  • [ 89894-44-0 ]
  • [ 99585-14-5 ]
YieldReaction ConditionsOperation in experiment
87%
Stage #1: at 0℃; for 0.75 h;
Stage #2: at 20℃;
A. A suspension of 2-chloro-6-methyl-benzoic acid (7.82 g, 45.8 MMOL) in thionyl chloride (20.0 mL, 275 MMOL), was immersed in an oil bath held at 85°C, and refluxed for 16 hours. The resulting pale brown solution was concentrated under reduced pressure to afford the acid chloride as a pale brown oil. This material was carried on to the ester formation without purification. The acid chloride (45.8 mmol from previous step) was dissolved in DICHLOROMETHANE (20 mL) and the mixture cooled in an ice bath. Methanol (10 mL, 247 MMOL) was added and the ice bath was then removed. HPLC of the reaction mixture 45 minutes after removal of the ice bath showed a 4: 1 mixture of starting acid: product ester. The reaction mixture was then treated with triethylamine (15 mL, 108 MMOL) dropwise over several minutes. The triethylamine addition was exothermic and led to the production of a lot of smoke in the reaction flask. After stirring overnight at ambient temperature HPLC indicated complete conversion to product. The reaction mixture was poured into a mixture of ether (200 mL) and saturated aqueous sodium hydrogen carbonate solution (100 mL). The layers were separated and the basic aqueous layer was extracted with ether (3 x 50 mL). The organic layers were combined and washed with brine, then dried (NA2SO4), filtered, and concentrated under reduced pressure to afford a yellow oil. The material was purified by flash chromatography eluting with a gradient from 0percent to 10percent ethyl acetate/hexane to afford 2-chloro-6-methylbenzoic acid methyl ester (7.38 g, 87percent yield) as a clear colorless liquid :'H-NMR (400 MHz, CDCI3) : 8 7.24-7. 19 (2H, m), 7.14-7. 08 (1H, m), 3.95 (3H, s), 2.32 (3H, s) ppm.
72% at 20℃; for 3 h; Preparation XVII: 2-chloro-6-dimethylaminomethyl-benzoic acid. Step 1. Synthesis of 2-bromomethyl-6-chloro-benzoic acid methyl ester.2-Chloro-6-methyl benzoic acid (5.8 g, 34.0 mmoles) was suspended in dichloromethane (100 ml). To the suspension was added DMF (250 mg, 3.4 mmoles) and then dropwise oxalyl chloride (3.9 ml, 44.2 mmoles). The resultant solution was stirred at ambient temperature for 24 hours. Further DMF (250 mg, 3.4 EPO <DP n="151"/>mmoles) and oxalyl chloride (3.9ml, 44.2 mmoles) was added to the reaction mixture, and the resultant solution stirred for a further 24 hours at ambient temperature. The reaction mixture was concentrated in vacuo. The residue was dissolved in methanol (100 ml) and stirred at ambient temperature for 3 hours. The reaction mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and sodium hydroxide solution (2N). The organic portion was washed with sodium hydroxide solution (2N), and then brine, dried (MgSO4), filtered and the concentrated in vacuo. The residue was purified by flash chromatography (eluent 3:5 EtOAc iPetrol to give 2-chloro-6-methyl-benzoic acid methyl ester as a yellow oil (4.5g, 72percent).
References: [1] Patent: WO2004/58717, 2004, A1, . Location in patent: Page 76.
[2] Patent: WO2006/77414, 2006, A1, . Location in patent: Page/Page column 149-150.
  • 2
  • [ 21327-86-6 ]
  • [ 74-88-4 ]
  • [ 99585-14-5 ]
References: [1] Patent: EP1408033, 2004, A1, . Location in patent: Page 115.
[2] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 1, p. 360 - 365.
  • 3
  • [ 21327-86-6 ]
  • [ 77-78-1 ]
  • [ 99585-14-5 ]
References: [1] Patent: US2010/249095, 2010, A1, . Location in patent: Page/Page column 91.
[2] Patent: US2007/32475, 2007, A1, . Location in patent: Page/Page column 32.
  • 4
  • [ 67-56-1 ]
  • [ 69190-56-3 ]
  • [ 201230-82-2 ]
  • [ 99585-14-5 ]
References: [1] Organic Process Research and Development, 2002, vol. 6, # 3, p. 220 - 224.
  • 5
  • [ 67-56-1 ]
  • [ 85070-46-8 ]
  • [ 201230-82-2 ]
  • [ 108-41-8 ]
  • [ 99585-14-5 ]
References: [1] Organic Process Research and Development, 2002, vol. 6, # 3, p. 220 - 224.
  • 6
  • [ 67-56-1 ]
  • [ 201230-82-2 ]
  • [ 5100-98-1 ]
  • [ 99585-14-5 ]
References: [1] Organic Process Research and Development, 2002, vol. 6, # 3, p. 220 - 224.
 

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