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Chemical Structure| 4693-91-8 Chemical Structure| 4693-91-8

Structure of 4-Methoxyphenylacetyl chloride
CAS No.: 4693-91-8

Chemical Structure| 4693-91-8

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Product Details of [ 4693-91-8 ]

CAS No. :4693-91-8
Formula : C9H9ClO2
M.W : 184.62
SMILES Code : O=C(Cl)CC1=CC=C(OC)C=C1
MDL No. :MFCD00075474
InChI Key :CXJOONIFSVSFAD-UHFFFAOYSA-N
Pubchem ID :2734688

Safety of [ 4693-91-8 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314
Precautionary Statements:P280-P305+P351+P338-P310
Class:8
UN#:3265
Packing Group:

Computational Chemistry of [ 4693-91-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 3
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.

2.01
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

2.4
Log Po/w (WLOGP)?

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

2.0
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.

1.74
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

2.67
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.16

Water Solubility

Log S (ESOL):?

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

-2.67
Solubility 0.396 mg/ml ; 0.00214 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.

-2.59
Solubility 0.47 mg/ml ; 0.00255 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

-3.5
Solubility 0.0591 mg/ml ; 0.00032 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.

-5.72 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

1.0 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)

1.25

Application In Synthesis of [ 4693-91-8 ]

* 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 [ 4693-91-8 ]

[ 4693-91-8 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 932-32-1 ]
  • [ 4693-91-8 ]
  • [ 1188327-78-7 ]
  • 2
  • [ 777-12-8 ]
  • [ 4693-91-8 ]
  • [ 1579991-09-5 ]
YieldReaction ConditionsOperation in experiment
44% at 110℃; for 0.166667h;Microwave irradiation; General procedure: Amide formation: (0088) The acid chloride (1 eq) formed on the corresponding 2-aminobenzothiazole (1 eq) is added introduced in a microwave vial. The vial is introduced in the microwave reactor and heated to the temperature for the time indicated in each case. Dichloromethane (50 mL) is added and extracted with a 0.1 M HCl (50 mL) solution. Next, the organic phase is washed with saturated NaHC03 solution (50 mL) and then with saturated NaCl (50 mL) solution. The organic phase is dried over anhydrous MgS04 and the solvent removed under reduced pressure. The residue obtained was purified by flash column chromatography using Isolera One equipment. In all cases a mixture of hexane and ethyl acetate was used as eluent. All the acid chlorides required for the synthesis of the amide derivatives were synthesised in situ except: 2-(4-chlorophenyl)acetyl chloride, 2-(2,5-dimethoxyphenyl)acetyl chloride and 2-phenylbutanoyl chloride, which were purchased directly from the company Sigma AldrichN-(6-trifluoromethylbenzothiazole-2-yl)-2-(4-methoxyphenyl)acetamide (3): (0090) Reagents: 2-(4-methoxyphenyl)acetyl chloride (21 1.7 mg, 1.2 mmol), 2-amino-6-trifluoromethylbenzothiazole (250 mg, 1.2 mmol) and THF (1 mL). Reaction conditions: 10 min under microwave irradiation at 110°C. Purification by flash column chromatography using hexane/ethyl acetate (3:1) to obtain a yellow solid. Yield: 184.8 mg, 44percent. Mp: 133°C-134°C 1H NMR (300 MHz, DMSO-d6) delta: 12.79 (s, 1 H), 8.47 (s, 1 H), 7.90 (d, J = 8.5 Hz, 1 H), 7.73 (d, J = 8.5 Hz, 1 H), 7.26 (d, J = 8.6 Hz, 2H), 6.89 (d, J = 8.7 Hz, 2H), 3.77 (s, 2H), 3.72 (s, 3H). 13C NMR (75 MHz, DMSO-d6) delta: 171.0, 161.1, 158.3, 151.3, 132.0, 130.4, 126.3, 124.5 (d, J = 272.2 Hz), 123.7 (d, J = 31.9 Hz), 122.9 (d, J = 3.7 Hz), 120.9, 119.8 (d, J = 4.3 Hz), 113.9, 55.0, 40.9. HPLC purity: >99percent. MS (ES) m/z: 367 [M+H]+. Elemental analysis (C17H13F3N2O2S): Theoretical percentC 55.73, percentH 3,58, percentN 7,65, percentS 8.75; Found percentC 55.48, percentH 3.31, percentN 7.44, percentS 8,97.
  • 3
  • [ 23218-93-1 ]
  • [ 4693-91-8 ]
  • methyl 3-amino-5-(2-(4-methoxyphenyl)acetamido)benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% To a separate oven-dried sample vial equipped with Teflon coated stir bar, 3- amino-5-nitrobenzoate (49 mg, 0.25 mmol), triethylamine (33 mg, 0.33 mmol), CH2C12 (1 mL) were sequentially added. The resulting solution was cooled to 0 C and 2-(4- methoxyphenyl)acetyl chloride (46 mg, 0.25 mmol) was added dropwise to the reaction mixture, then slowly warmed to ft and stirred for 2 h. After the reaction, H20 (1 mL) was added, the organic phase was separated and the volatiles were removed under vacuum. To the residue was transferred iron nanomaterial (12 mg, 0.8%) and 2 wt % TPGS-750-M (1 mL), and stirred at ft for 1 mm. The septum was removed and NaBH4 (21 mg, 0.55 mmol) was slowly added to the reaction mixture. During addition of NaBH4, the reaction mixture turned black with evolution of hydrogen gas. The vial was covered and the contents stirred vigorously for 8 h. The mixture was then extracted with EtOAc (0.3 mL x 2), concentrated in vacuo, and purified by flash chromatography over silica gel with EtOAc/hexanes (15/85 to 30/70) to yield methyl 3-amino-5-(2-(4-methoxyphenyl)acetamido)benzoate 56 (63 mg, 0.2 mmol, 80%) as a colorless oil; Spectral data matched the literature. GC-MS, mlz: 314 [Mj.
  • 4
  • [ 65826-95-1 ]
  • [ 4693-91-8 ]
  • C18H19NO2 [ No CAS ]
 

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