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Chemical Structure| 886374-01-2 Chemical Structure| 886374-01-2

Structure of 886374-01-2

Chemical Structure| 886374-01-2

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Product Details of [ 886374-01-2 ]

CAS No. :886374-01-2
Formula : C6H5ClFNO
M.W : 161.56
SMILES Code : COC1=NC=C(Cl)C=C1F
MDL No. :MFCD07375056
InChI Key :URXHTRZQQSCUAD-UHFFFAOYSA-N
Pubchem ID :46738734

Safety of [ 886374-01-2 ]

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

Computational Chemistry of [ 886374-01-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 35.7
TPSA ?

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

22.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.08
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

1.89
Log Po/w (WLOGP)?

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

2.3
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.

1.6
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

2.41
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.06

Water Solubility

Log S (ESOL):?

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

-2.41
Solubility 0.628 mg/ml ; 0.00389 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.

-1.98
Solubility 1.7 mg/ml ; 0.0105 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

-3.04
Solubility 0.148 mg/ml ; 0.000918 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.

-5.94 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)

1.78

Application In Synthesis of [ 886374-01-2 ]

* 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 [ 886374-01-2 ]

[ 886374-01-2 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 886374-01-2 ]
  • [ 73183-34-3 ]
  • [ 1310384-35-0 ]
YieldReaction ConditionsOperation in experiment
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; for 21h;Inert atmosphere; A stirred mixture of <strong>[886374-01-2]5-chloro-3-fluoro-2-methoxypyridine</strong> (0.33 g, 2.0 mmol), bis(pinacolato)diboron (0.58 g, 2.3 mmol), [l,l-bis(diphenylphosphino)- ferrocene]palladium(II) chloride, complex with DCM (0.17 g, 0.21 mmol), and potassium acetate (0.61 g, 6.17 mmol) in dry 1,4-dioxane (8.0 mL) was purged three times with argon and placed under vacuum three times. The mixture was heated to and monitored with LC-MS and TLC. After 21 h, the reaction was cooled to rt then filtered through Celite. The organic solvent was removed under reduced pressure, and the black residue was identified as 3-fluoro-2- methoxy-5-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)pyridine and used without purification. Mass Spectrum (pos.) m/e: 254.0 (M+H)+.
1.01 g With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; dichloromethane; at 100℃;Inert atmosphere; Nitrogen gas was purged through a mixture of 5-chloro-3-fluoro-2-methoxy- pyridine (700 mg, 4.33 1 mmol), bis(pinacolato)diboron (1.32 g, 5.198 mmol) and potassium acetate (1.27 g, 12.993 mmol) in 1,4-dioxane (10 mL) for 30 mm. Then, [1,1-bis- (diphenylphosphino)-feffocene]palladium(II)chloride complex with DCM (353 mg, 0.433 mmol) was added. Nitrogen gas purging was continued for another 5 mm. The reaction mixture was heated at 100 C overnight. The reaction was monitored by LCMS. After completion of reaction, the mixture was cooled to RT, then filtered through a celite bed. The organic solvent was removed under reduced pressure and the residue obtained was triturated with pentane. The pentane layer was taken and concentrated to obtain 1.01 g of 3-fluoro-2- methoxypyridine-5-boronic acid pinacol ester which was used as such for next step without further purification.
  • 2
  • [ 886374-01-2 ]
  • 5,7-difluoro-N-(5'-fluoro-6'-methoxy-6-morpholino-3,3'-bipyridin-4-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine [ No CAS ]
  • 3
  • [ 886374-01-2 ]
  • 3-(5-fluoro-6-methoxypyridin-3-yl)-1-(6-methyl-1,2,3,4-tetrahydroquinolin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine [ No CAS ]
  • 4
  • [ 886374-01-2 ]
  • 3-(5-fluoro-6-methoxypyridin-3-yl)-1-(1,2,3,4-tetrahydronaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine [ No CAS ]
  • 5
  • [ 886374-01-2 ]
  • 1-(3-(4-amino-3-(5-fluoro-6-methoxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-6-methyl-3,4-dihydroquinolin-1(2H)-yl)prop-2-en-1-one [ No CAS ]
  • 6
  • [ 124-38-9 ]
  • [ 886374-01-2 ]
  • C7H5ClFNO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% To a solution of compound 2 (3.6g, 17.56mmol, 1 eq) in Dry THF (20ml_), a solution of nBuLi (1.6M in hexane, 1 .5eq) was added dropwise over 10min at -78C and stirred 30min at the same temp. After, 30min crushed dry ice was added portion wise to the above solution at -78C. Then, the reaction mixture was allowed to warm up to RT over 2h. After 2h, the reaction mixture was cooled to 0C and neutralized by conc.HCI. Then, the reaction mixture was concentrates under reduced pressure to give a crude product. The crude product was dissolved in 5M NaOH solution and washed with ether; the aqueous layer was cooled to 0C and acidified to pH 5-6 by cone. HCI. A precipitate formed. The precipitate was filtered and washed with ether to give compound 3 (2.7g, 75.0%) as a white solid. LCMS: m/z 204.1 (M-1 )
  • 7
  • [ 89402-43-7 ]
  • [ 886374-01-2 ]
YieldReaction ConditionsOperation in experiment
69.89% With sodium methylate; In methanol; at 65℃; for 2h; To a solution of compound 1 (1 g, 6.687mmol, 1 eq) in Dry Methanol (5ml_), a solution of 30% NaOMe (1 .8ml_, 10.03mmol, 1.5eq) was added dropwise and the reaction mixture was heated to 65C for 2h (Reaction was monitored by 1 HNMR and LCMS). Then, the reaction mixture was cooled to RT and concentrated under reduced pressure to give a residue. Residue was dissolved in EtOAc and washed with water. The separated organic layer was dried over Na2S04 and concentrated under reduced pressure to give compound 2 (750mg, 69.89%) as colorless liquid; which was sufficiently pure to use for next step.
  • 8
  • [ 886374-01-2 ]
  • C11H14ClFN2O3 [ No CAS ]
  • 9
  • [ 886374-01-2 ]
  • 5-chloro-3-fluoro-2-methoxypyridin-4-amine [ No CAS ]
 

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