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Chemical Structure| 873107-98-3 Chemical Structure| 873107-98-3

Structure of 873107-98-3

Chemical Structure| 873107-98-3

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Product Details of [ 873107-98-3 ]

CAS No. :873107-98-3
Formula : C6H3F3IN
M.W : 272.99
SMILES Code : FC(F)(F)C1=NC=C(I)C=C1
MDL No. :MFCD11226772
InChI Key :GBAXFWLQMVBNMV-UHFFFAOYSA-N
Pubchem ID :45598118

Safety of [ 873107-98-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P305+P351+P338

Computational Chemistry of [ 873107-98-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 41.96
TPSA ?

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

12.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.94
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

2.42
Log Po/w (WLOGP)?

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

3.86
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.

2.49
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

3.34
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.81

Water Solubility

Log S (ESOL):?

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

-3.39
Solubility 0.11 mg/ml ; 0.000403 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.

-2.33
Solubility 1.27 mg/ml ; 0.00464 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

-3.86
Solubility 0.0376 mg/ml ; 0.000138 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.

-6.25 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<0.0
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)

1.9

Application In Synthesis of [ 873107-98-3 ]

* 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 [ 873107-98-3 ]

[ 873107-98-3 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 106877-33-2 ]
  • [ 873107-98-3 ]
YieldReaction ConditionsOperation in experiment
87%
Stage #1: With hydrogenchloride; sodium nitrite In water at -5 - 5℃; for 0.166667 h;
Stage #2: With potassium iodide In water at -5 - 10℃;
Step 1: 5-iodo-2-(trifluoromethyl)pyridine [0251] A solution of 6-(trifluoromethyl)pyridin-3-amine (9.96 g, 0.062 mol) in 5N HC1 (70 mL) was cooled to -5°C and sodium nitrite (6.39 g, 0.093 mol) in 30 mL of water was added dropwise while maintaining the internal temperature below 5°C. After 10 min, KI (22.5 g, 0.136 mol) in 30 mL of water was added dropwise at -5°C while maintaining the internal temperature below 10°C over the course of the addition. The reaction mixture was warmed to rt and 250 mL of EtOAc was added. The pH of the aqueous layer was adjusted to 11 by the addition of 50 mL of 6N NaOH, the layers were separated, and the organic layer was washed with 120 mL of 0.3M Na2S203. The EtOAc layer was concentrated and the concentrate was purified by column chromatography over silica gel (hexane/ EtOAc =25/1) to afford the title compound as a white solid (14.6 g, 87percent). MS (ESI) calcd for C6H3F3IN: 273.0; found: 274.0[M+H]. 1H NMR (400 MHz, CDC13) δ 8.96 (s, 1H), 8.22 (d, J = 8.2 Hz, 1H), 7.47 (d, J = 8.2 Hz, 1H).
87%
Stage #1: With hydrogenchloride; sodium nitrite In water at -5 - 5℃; for 0.166667 h;
Stage #2: With potassium iodide In water at -5 - 20℃;
A solution of 6—(triflucron’iethyi)pyridin—3—arnine (c.96 g. 0.062 moi) in sN HCI (70 mL) was cooled to -5°C and sodium nitrite (6.39 g, 0.093 mol) in 30 niL of water was added dtopwise \percent bile rnamtaanrng the internal temper ilure helms 5 C. \ftei 10 mm K (22 5 g 0 1 o mol) in 30 niL of water uac added dropi 1st at —5°C while inarntauung the inttrnaltemperature below 10 °C over the course of the addition. [he reaction mixture was warmed to rt and 250 mL of EtOAc was added. The pH of the aqueous layer was adjusted to 11 by the addition of So ml of ON ‘4aOH Ihe oiganic laser ws sepaiated and ashed ;kith 120 mL of 0 M \&S2O, Tin. EtOc laser was oncntrated and the onc,.entratc was purifitd b Lolumo chronwogiaphy O\ ei sdica gel he,.ane 1 ii) .c 2 I) to aifoid the title compound as a white solid (14.6 g, 87percent). MS (ES) ealcd for C6H3F31N: 273.0; found: 274.0 [M±HJ. ‘H NMR (400 MHz. CDCL) ii 8.96 (s. iS). 8.22 (d. J:::: 8.2 Hz, JHI, 7.47 (d. J 8.2 Hz, iii).
References: [1] Patent: WO2015/187845, 2015, A1, . Location in patent: Paragraph 0251.
[2] Patent: WO2016/44323, 2016, A1, . Location in patent: Paragraph 0347.
[3] Patent: WO2006/4533, 2006, A1, . Location in patent: Page/Page column 25.
  • 2
  • [ 436799-32-5 ]
  • [ 873107-98-3 ]
References: [1] Angewandte Chemie - International Edition, 2019, [2] Angew. Chem., 2019, vol. 131, # 5, p. 1472 - 1476,5.
[3] Journal of the American Chemical Society, 2015, vol. 137, # 33, p. 10480 - 10483.
 

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