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Chemical Structure| 383134-85-8 Chemical Structure| 383134-85-8

Structure of 383134-85-8

Chemical Structure| 383134-85-8

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Product Details of [ 383134-85-8 ]

CAS No. :383134-85-8
Formula : C9H9FO3
M.W : 184.16
SMILES Code : O=C(O)CC1=CC(F)=CC=C1OC
MDL No. :MFCD00671771
Boiling Point : No data available
InChI Key :WGZCWKASVDIAOH-UHFFFAOYSA-N
Pubchem ID :302684

Safety of [ 383134-85-8 ]

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

Computational Chemistry of [ 383134-85-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 44.44
TPSA ?

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

46.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.67
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

1.46
Log Po/w (WLOGP)?

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

1.88
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.

1.79
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

1.98
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.76

Water Solubility

Log S (ESOL):?

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

-2.05
Solubility 1.66 mg/ml ; 0.00901 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.

-2.04
Solubility 1.67 mg/ml ; 0.00905 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

-2.58
Solubility 0.481 mg/ml ; 0.00261 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.

-6.39 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)

1.71

Application In Synthesis of [ 383134-85-8 ]

* 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 [ 383134-85-8 ]

[ 383134-85-8 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 383134-85-8 ]
  • 8-amino-5-(4-fluorophenyl)-11-methyl-2,4,5,11-tetrahydro-1H-2,5,11-triazadibenzo[cd,h]azulen-1-one [ No CAS ]
  • [ 76-05-1 ]
  • 2-(5-fluoro-2-methoxyphenyl)-N-(5-(4-fluorophenyl)-11-methyl-1-oxo-2,4,5,11-tetrahydro-1H-2,5,11-triazadibenzo[cd,h]azulen-8-yl)acetamide trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% Example 65 2-(5-fluoro-2-methoxyphenyl)-N-(5-(4-fluorophenyl)-11-methyl-1-oxo-2,4,5,11-tetrahydro-1H-2,5,11-triazadibenzo[cd,h]azulen-8-yl)acetamide [0760] A stock solution of Example 23e and N,N-diisopropylethylamine (0.09 M and 0.25 M in N,N-dimethylacetamide, respectively, 450 muL, 0.2 mmol Example 23e and 0.6 mmol N,N-diisopropylethylamine), 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (0.14 M in N,N-dimethylacetamide, 450 muL, 0.3 mmol), and <strong>[383134-85-8]2-(5-fluoro-2-methoxyphenyl)acetic acid</strong> (0.40 M in N,N-dimethylacetamide, 125 muL, 0.24 mmol) were aspirated from their respective source vials, mixed through a perfluoroalkoxy mixing tube (0.2 mm inner diameter), and loaded into an injection loop. The reaction segment was injected into the flow reactor (Hastelloy coil, 0.75 mm inner diameter, 1.8 mL internal volume) set at 100 C., and passed through the reactor at 180 muL min-1 (10 minute residence time). Upon exiting the reactor, the reaction mixture was loaded directly into an injection loop and purified using reverse phase HPLC(C8, acetonitrile/water (0.1% TFA), 5-100%) to give 0.0243 g (91%) of the title compound as the TFA salt. 1H NMR (400 MHz, DMSO-d6/D2O) delta 10.28 (s, 1H), 8.12 (d, J=2.44 Hz, 1H), 7.65 (s, 1H), 7.42 (dd, J=8.54, 2.44 Hz, 1H), 7.20 (d, J=8.54 Hz, 1H), 7.11 (m, 2H), 7.04 (s, 1H), 7.01 (m, 1H), 6.83 (m, 2H), 6.48 (m, 2H), 5.02 (d, J=15.56 Hz, 1H), 4.18 (d, J=15.87 Hz, 1H), 4.04 (s, 3H), 3.79 (s, 3H), 3.70 (s, 2H). MS (APCI+) m/z 527.1 (M+H)+.
  • 2
  • [ 383134-85-8 ]
  • 4-amino-N-tert-butylpyridine-2-carboxamide [ No CAS ]
  • N-tert-butyl-4-[[2-(5-fluoro-2-methoxyphenyl)acetyl]amino]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
A solution of 2-(5-chloro-2-methoxy-phenyl)acetic acid (2.26 g, 11.27 mmol) in thionylchloride (8.13 mL, 92.21 mmol) was heated at 70 00 for 30 minutes. After cooling to roomtemperature, excess thionyl chloride was removed in vacuo, azeotroping with toluene. The resulting residue was dissolved in DCM (5 mL) and added to a solution of 4-amino-N-tert- butyl-pyridine-2-carboxamide (step 1) (2.0 g, 10.25 mmol) and DIPEA (2.15 mL, 12.29 mmol) in DCM (25 mL). The mixture stirred at room temperature for 1 hour and then dilutedwith water (50 mL) and extracted with DCM. The combined organic extracts were washed with brine (50 mL), dried over Na2504 and concentrated in vacuo. The crude residue was purified by chromatography on silica eluting with 0-50% EtOAc in heptane to afford the titled compound as a pale orange powder.1H NMR (500 MHz, Chloroform-d) O 8.39 (d, J = 5.6 Hz, 1H), 8.20 (dd, J = 5.6, 2.2 Hz, 1H), 8.10 (brs, 1H), 7.98 (brs, 1H), 7.56 (d, J = 2.1 Hz, 1H), 7.29-7.26 (m, 2H), 6.89 (d,J = 9.5 Hz, 1H), 3.94 (5, 3H), 3.70 (5, 2H), 1.47 (5, 9H).LC-MS (Method E): Rt 1.21 mins; MS m/z 376.1/ 378.1 = [M+H]+ (92% 215nm)
  • 3
  • [ 383134-85-8 ]
  • 3-[[2-(5-fluoro-2-methoxyphenyl)acetyl]amino]benzoic acid [ No CAS ]
  • 4
  • [ 383134-85-8 ]
  • 3-[[2-(5-fluoro-2-hydroxyphenyl)acetyl]amino]benzoic acid [ No CAS ]
  • 5
  • [ 582-33-2 ]
  • [ 383134-85-8 ]
  • ethyl 3-[[2-(5-fluoro-2-methoxyphenyl)acetyl]amino]benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In 1,4-dioxane; ethyl acetate; at 20℃; for 2h; A mixture of ethyl 3-aminobenzoate (300 mg, 1.82 mmol) and 2-(5-fluoro-2-methoxy- phenyl)acetic acid (334 mg, 1.82 mmol) in 1,4-dioxane (5 mL) was treated with 50% T3P solution in EtOAc (2.31 mL, 1.82 mmol) and TEA (634 muL, 3.63 mmol). After stirring at room temperature for 2 hours, the mixture was partitioned between water (20 mL) and EtOAc (20 mL). The organic layer was separated, dried over Na2SO4 and concentrated in vacuo. Purification of the crude residue by chromatography on silica eluting with EtOAc in heptane afforded the titled compound as a white solid.1H NMR (500 MHz, DMSO-d6) delta 10.31 (s, 1H), 8.26 (t, J = 1.8 Hz, 1H), 7.86- 7.82 (m, 1H , 7.63 dt, J = 7.79, 1.2 Hz, 1H , 7.45 t, J = 7.9 Hz, 1H), 7.11 (dd, J = 9.2, 3.1 Hz, 1H),Hz, 1H), 4.31 (q, J = 7.1 Hz, 2H), 3.75 [M+H]+ (100% 215nm)
 

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