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Structure of 871826-12-9

Chemical Structure| 871826-12-9

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Product Details of [ 871826-12-9 ]

CAS No. :871826-12-9
Formula : C7H8ClF3N2
M.W : 212.60
SMILES Code : Cl.NCC1=NC=C(C=C1)C(F)(F)F
MDL No. :MFCD05863878
InChI Key :HVXHWBMLTSDYGK-UHFFFAOYSA-N
Pubchem ID :17749874

Safety of [ 871826-12-9 ]

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

Computational Chemistry of [ 871826-12-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.29
Num. rotatable bonds 2
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 43.88
TPSA ?

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

38.91 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

1.43
Log Po/w (WLOGP)?

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

3.36
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.

1.29
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

1.96
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.61

Water Solubility

Log S (ESOL):?

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

-2.27
Solubility 1.15 mg/ml ; 0.00539 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.

-1.85
Solubility 2.99 mg/ml ; 0.0141 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very 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

-2.95
Solubility 0.236 mg/ml ; 0.00111 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.

-6.58 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

0.0
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)

1.78

Application In Synthesis of [ 871826-12-9 ]

* 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 [ 871826-12-9 ]

[ 871826-12-9 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 1029634-31-8 ]
  • [ 871826-12-9 ]
  • [ 119-67-5 ]
  • [ 1198116-89-0 ]
  • 2
  • [ 871826-12-9 ]
  • [ 1448039-26-6 ]
  • [ 1448040-74-1 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 2h; General procedure: The carboxylic acid 8 is dissolved in DMF and 2 eq. of the corresponding amine component, 1.5 eq. of HATU and 3 eq. of triethylamine are added. The reaction mixture is stirred at rt until TLC and/or LCMS indicate complete consumption of the starting material (2 h), then water is added. The formed precipitate is filtered off, washed with water and dried in a vacuum drying cabinet at 40C. If appropriate, the product is purified by preparative HPLC.
  • 3
  • [ 32315-10-9 ]
  • [ 871826-12-9 ]
  • 5-amino-4,6-dichloro-3,3-dimethyl-1-indanone [ No CAS ]
  • 1-(4,6-dichloro-3,3-dimethyl-1-oxo-2,3-dihydro-1H-inden-5-yl)-3-[5-(trifluoromethyl)-2-pyridinyl]methyl}urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
100 mg To a tetrahydrofuran (4 mL) solution of the compound (200 mg) produced in Example 33, triphosgene (267 mg) and diisopropylethylamine (156 muL) were added, and the resulting mixture was stirred at room temperature for 20 hours, and then concentrated under reduced pressure. To the resulting residue, tetrahydrofuran (3 mL) was added, and then, <strong>[871826-12-9]1-[5-(trifluoromethyl)-2-pyridinyl]methanamine hydrochloride</strong> (583 mg) () (173 mg) and diisopropylethylamine (176 muL) were added, followed by stirring at room temperature for 20 hours. The reaction mixture was diluted with a saturated aqueous sodium hydrogen carbonate solution, and extraction was performed with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate = 40:60), whereby the title compound having the following physical property values was obtained (100 mg). TLC: Rf 0.29 (hexane:ethyl acetate = 1:1); 1H-NMR (DMSO-d6): delta 1.53, 2.71, 4.50, 7.25, 7.60, 7.67, 8.26, 8.67, 8.91.
  • 4
  • [ 871826-12-9 ]
  • 2-fluoro-4-nitro-N<SUP>1</SUP>-((5-(trifluoromethyl)pyridin-2-yl)methyl)benzene-1,3-diamine [ No CAS ]
  • 5
  • [ 871826-12-9 ]
  • [ 164341-39-3 ]
  • 6
  • [ 871826-12-9 ]
  • ethyl (2-amino-3-fluoro-4-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)phenyl)carbamate [ No CAS ]
  • 7
  • [ 871826-12-9 ]
  • C13H12F4N4 [ No CAS ]
  • 8
  • [ 871826-12-9 ]
  • cyclopropyl (2-amino-3-fluoro-4-(((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)phenyl)carbamate [ No CAS ]
  • 9
  • [ 871826-12-9 ]
  • 1-(ethoxycarbonyl)-4-oxocyclohexanecarboxylic acid [ No CAS ]
  • ethyl 4-oxo-1-(((5-(trifluoromethyl)pyridin-2-yl)methyl)carbamoyl)cyclohexanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.45 g With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; To a mixture of Example 234A (0.37 g, 1.727 mmol), (5-(trifluoromethyl)pyridin-2- yl)methanamine, hydrochloric acid (0.459 g, 2.159 mmol), and N-ethyl-N-isopropylpropan-2- amine (1.056 mL, 6.05 mmol) in N,N-dimethylformamide (7.5 mL), 2-(3H-[l ,2,3]triazolo[4,5- Z?]pyridin-3-yl)- l ,l ,3,3-tetramethylisouronium hexafluorophosphate(V) (0.985 g, 2.59 mmol) was added, and the mixture was stirred at ambient temperature overnight. Water was added, and the aqueous phase was extracted with dichloromethane. The organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated, and the residue was purified on silica gel (5-100% ethyl acetate in heptane) to give 0.45 g of the title compound. JH NMR (400 MHz, DMSO- ) delta ppm 8.83 (d, J = 2.3 Hz, 1H), 8.64 (t, J = 5.9 Hz, 1H), 8.13 (ddd, J = 21.1 , 8.4, 2.4 Hz, 1H), 7.39 (dd, J = 19.7, 8.3 Hz, 1H), 4.45 (d, J = 5.8 Hz, 2H), 4.20 - 4.03 (m, 2H), 2.38 - 2.21 (m, 8H), 1.15 (td, J = 7.1, 1.8 Hz, 3H); MS (ESI+) m/z 373.4 (M+H)+.
  • 10
  • [ 211693-73-1 ]
  • [ 871826-12-9 ]
  • 2-fluoro-4-nitro-N<SUP>1</SUP>-((5-(trifluoromethyl)pyridin-2-yl)methyl)benzene-1,3-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% 2- (0257) (Aminomethyl)-5-(trifluoromethyl)pyridine hydrochloride (0.180 g, 0.804 mmol) was neutralized with 1 M NaOH (0.84 mL). The resulting aqueous solution was extracted with CH2CI2 (3 x). The combined organic layers were dried (Na2S04), and concentrated in vacuo to give a yellowish oil that was dissolved in dry DMSO (1.6 mL) and treated with 2,3-difluoro-6-nitroaniline 4a (0.144 g, 0.804 mmol) followed by Et3N (0.12 mL, 0.885 mmol) and L (8 mg, 0.03 mmol, 0.04 equiv). The reaction mixture was heated to 120 C for 30 h, cooled to room temperature, diluted with water (15 mL) and extracted with CH2CI2 (3 x 10 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (Na2S04), filtered and concentrated under reduced pressure. The residue was purified by chromatography on S1O2 (acetone/hexanes, 1:8 to 1:5 to 1:4, containing Et3N(0.2%)) to give 5i (0.20 g, 75 %) as a yellow solid: Mp 138.2-138.5 C; IR (ATR) 3484, 3370, 1629, 1607, 1551, 1482, 1325, 1282, 1251, 1126, 1077, 1018, 755 cm 1; NMR (400 MHz, CDCL) d 8.88 (s, 1 H), 7.95-7.87 (m, 2 H), 7.44 (d, 1 H, 7 = 8.4 Hz), 6.10-6.05 (m, 3 H), 5.72 (br s, 1H), 4.66 (d, 2 H, 7 = 5.6 Hz); 13C NMR (100 MHz, CDCL) d 160.4, 146.5 (q, 7 = 4.0 Hz), 140.7 (d, 7 = 9.0 Hz), 138.1 (d, 7 = 227.0 Hz), 135.3 (d, 7 = 13.0 Hz), 134.2 (q, 7 = 3.5 Hz), 126.0 (q, 7 = 33.0 Hz), 125.6 (d, 7 = 3.0 Hz), 123.7 (d, 7 = 3.0 Hz), 123.5 (q, 7 = 271.0 Hz), 121.3, 100.9 (d, 7 = 3.0 Hz), 47.8; 19F NMR (376 MHz , CDCL) d -62.3 (s, 3 F), -160.5 (s, 1 F); HRMS (HESI) m/z calcd for CI HION402F4 [M+H]+ 330.0813, found 330.0811.
 

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