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Chemical Structure| 403-33-8 Chemical Structure| 403-33-8

Structure of 403-33-8

Chemical Structure| 403-33-8

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Product Details of [ 403-33-8 ]

CAS No. :403-33-8
Formula : C8H7FO2
M.W : 154.14
SMILES Code : O=C(OC)C1=CC=C(F)C=C1
MDL No. :MFCD00017959
InChI Key :MSEBQGULDWDIRW-UHFFFAOYSA-N
Pubchem ID :67878

Safety of [ 403-33-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 403-33-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 37.68
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.

2.07
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

2.28
Log Po/w (WLOGP)?

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

2.03
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.

2.36
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

2.11
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.17

Water Solubility

Log S (ESOL):?

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

-2.5
Solubility 0.483 mg/ml ; 0.00314 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.

-2.47
Solubility 0.523 mg/ml ; 0.00339 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

-2.74
Solubility 0.282 mg/ml ; 0.00183 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.

-5.62 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)

1.18

Application In Synthesis of [ 403-33-8 ]

* 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 [ 403-33-8 ]

[ 403-33-8 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 403-33-8 ]
  • [ 79286-79-6 ]
  • [ 953435-47-7 ]
YieldReaction ConditionsOperation in experiment
65% With potassium carbonate; In dimethyl sulfoxide; at 130℃; for 18h; Example 37a; (S)-N-(4-Aminobiphenyl-3-yl)-4-(3-aminopyrrolidin-l-yl)benzamide (327); Scheme 37; Step 1 : (SVMethyl 4-(3-aminopyrrolidin-l-v0benzoate (323); [0940] K2CO3 (7.71 g, 55.84 mmol) was added to a solution of (S)-pyrrolidin-3 -amine (5.0 g,58.04 mmol) and methyl 4-fluorobenzoate (8.6 g, 55.81 mmol) in DMSO (20 mL). The reaction mixture was stirred for 18 h at 130 0C in a sealed tube. The reaction mixture was cooled, diluted with AcOEt and H2O, and extracted with AcOEt (3 times). The extract was washed with water,NH4Cl and brine, dried over MgSO4, filtered and concentrated to give the title compound 323(7.98 g, 65% yield) as a pink solid.[0941] 1H NMR (DMSO-de) delta (ppm): 7.75 (d, J = 9.0 Hz, 2H), 6.52 (d, J = 9.0 Hz, 2H), 3.74(s, 3H), 3.60-3.55 (m, IH), 3.45-3.41 (m, 2H), 3.32-3.25 (m, IH), 2.97-2.93 (m, IH), 2.09-2.01(m, IH), 1.72-1.68 (m, IH). LRMS calc. 220.1; found 221.1 (MH)+.
  • 2
  • 4-(carboxylic acid methyl ester)-N,N,N-trimethylanilinium trifluoromethanesulfonate [ No CAS ]
  • [ 593-53-3 ]
  • [ 403-33-8 ]
  • [ 1202-25-1 ]
  • 3
  • [ 403-33-8 ]
  • [ 3347-62-4 ]
  • [ 934290-28-5 ]
YieldReaction ConditionsOperation in experiment
12% With 40% KF/Al2O3 ;18-crown-6 ether; In dimethyl sulfoxide; at 120℃; for 48h; A compound wherein a methyl group was introduced into the 5-position of the pyrazole ring of XO-TT469 was synthesized. A pyrazole, XO-TT485, was prepare by condensation reaction of 1-phenyl-1,3-butanedione and hydrazine. And a 4-phenylcarboxylic acid unit was introduced (the following scheme).; XO-TT486A; XO-TT485 (300 mg, 1.90 mmol) was dissolved in dimethyl sulfoxide (10 mL), and to the solution were added 40% potassium fluoride-alumina (600 mg), methyl 4-fluorobenzoate (492 mL, 3.80 mmol) and 18-crown-6 (100 mg, 0.380 mmol). The mixture was stirred at 120C for 2 days. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The residue was purified by column chromatography on silica gel (hexane : ethyl acetate = 10 : 1 to 5 : 1) to give XO-TT486A as a white solid (64.9 mg, 12% yield).
  • 4
  • [ 234082-35-0 ]
  • 4,4,6-trimethyl-1,3,2-dioxaborinane [ No CAS ]
  • [ 1214273-30-9 ]
  • [ 403-33-8 ]
  • 5
  • [ 403-33-8 ]
  • [ 4522-35-4 ]
  • [ 1621525-02-7 ]
YieldReaction ConditionsOperation in experiment
INTERMEDIATE 7 Methyl 4-(3 -iodo- 1 H-p yrazol- 1 -yPbenzoate To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (0.7 g, 3.61 mmol) in DMSO (18.0 mL) was added sodium hydride (60% disp. in oil (0.173 g, 4.33 mmol), and the resulting mixture was stirred for 0.5 h before adding methyl 4- fluoro benzoate (0.556 g, 3.61 mmol). The reaction mixture was stirred at 90 C overnight. The reaction was quenched by the addition of water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO, 40 g, 0-20 % EtOAc in hexanes) to afford methyl 4-(3-iodo-lH-pyrazol-l-yl)benzoate, as a white solid. LCMS calc. - 328.97; found = 328.96 (M+H)+. NMR (500 MHz, CDC13): delta 8.12 (m, 2 H); 7.81 (d, J= 2.4 Hz, 1 H); 7.76 (m, 2 H); 6.65 (m, 1 H); 3.94 (s, 3 H).
  • 6
  • [ 403-33-8 ]
  • [ 124-40-3 ]
  • [ 1202-25-1 ]
  • 7
  • [ 403-33-8 ]
  • [ 68-12-2 ]
  • [ 1202-25-1 ]
  • 8
  • [ 62671-89-0 ]
  • [ 403-33-8 ]
  • [ 2164-67-2 ]
  • C19H18FN7 [ No CAS ]
  • 9
  • [ 62671-89-0 ]
  • [ 403-33-8 ]
  • [ 2164-67-2 ]
  • C18H14FN5OS [ No CAS ]
 

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