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Chemical Structure| 315180-17-7 Chemical Structure| 315180-17-7

Structure of 315180-17-7

Chemical Structure| 315180-17-7

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Product Details of [ 315180-17-7 ]

CAS No. :315180-17-7
Formula : C6H6FNO
M.W : 127.12
SMILES Code : OCC1=NC(F)=CC=C1
MDL No. :MFCD07783827
InChI Key :OWTCZNAMUJIMOC-UHFFFAOYSA-N
Pubchem ID :12045263

Safety of [ 315180-17-7 ]

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

Computational Chemistry of [ 315180-17-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 30.32
TPSA ?

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

33.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.26
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

-4.91
Log Po/w (WLOGP)?

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

0.98
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.

0.31
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

1.63
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.15

Water Solubility

Log S (ESOL):?

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

2.04
Solubility 13900.0 mg/ml ; 109.0 mol/l
Class?

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

Highly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

4.85
Solubility 8970000.0 mg/ml ; 70500.0 mol/l
Class?

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

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

-2.09
Solubility 1.03 mg/ml ; 0.00807 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.

-10.56 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

2.0
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<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)

1.54

Application In Synthesis of [ 315180-17-7 ]

* 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 [ 315180-17-7 ]

[ 315180-17-7 ] Synthesis Path-Downstream   1~16

  • 1
  • [ 34798-95-3 ]
  • [ 315180-17-7 ]
  • 6-(6-fluoro-pyridin-2-ylmethoxy)-9<i>H</i>-purin-2-ylamine [ No CAS ]
  • 2
  • [ 315180-17-7 ]
  • 1-(2-amino-9H-purin-6-yl)-4-(dimethylamino)pyridin-1-ium chloride [ No CAS ]
  • 6-(6-fluoro-pyridin-2-ylmethoxy)-9<i>H</i>-purin-2-ylamine [ No CAS ]
  • 3
  • C9H8FNO4 [ No CAS ]
  • [ 315180-17-7 ]
  • 4
  • [ 315180-16-6 ]
  • [ 315180-17-7 ]
  • 5
  • [ 402-69-7 ]
  • [ 315180-17-7 ]
  • 6
  • [ 407-22-7 ]
  • [ 315180-17-7 ]
  • 8
  • [ 315180-17-7 ]
  • [ 315180-16-6 ]
YieldReaction ConditionsOperation in experiment
With thionyl chloride; In dichloromethane; at 20℃; for 2h; Production Example 7-3: 2-Chloromethyl-6-fluoropyridine: Thionyl chloride (25 mL) was added to a dichloromethane solution (80 mL) of the compound (1.1 g) obtained in Production Example 7-2, and stirred at room temperature for 2 hours. The solvent was evaporated off under reduced pressure, ethyl acetate was added to the resulting residue, and the organic layer was washed with aqueous saturated sodium hydrogencarbonate solution. The organic layer was dried with anhydrous magnesium sulfate, and the solvent was evaporated off under reduced pressure to obtain the entitled compound (990 mg).
  • 9
  • 2-chloro-4-(pyridin-3-yl)-5,6,7,8-tetrahydroquinoline [ No CAS ]
  • [ 315180-17-7 ]
  • 2-[(6-fluoropyridin-2-yl)methoxy]-4-(pyridin-3-yl)-5,6,7,8-tetrahydroquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
26 mg With 4,5-bis-(di-tert-butyl-phosphanyl)-9,9-dimethyl-9H-xanthene; tris(dibenzylideneacetone)dipalladium(0) chloroform complex; caesium carbonate; In toluene; at 100℃; for 4h;Inert atmosphere; Example 86 2-[(6-Fluoropyridin-2-yl)methoxy]-4-(pyridin-3-yl)-5,6,7,8-tetrahydroquinoline To 2-chloro-4-(pyridin-3-yl)-5,6,7,8-tetrahydroquinoli ne (65 mg), <strong>[315180-17-7](6-fluoropyridin-2-yl)methanol</strong> (34 mg), Pd2(dba)3·CHCl3 (17 mg), t-Bu-X-Phos (18 mg) and cesium carbonate (174 mg) was added toluene (2.6 mL), and the mixture was degassed, then stirred at 100C for 4 hours under Ar atmosphere. The mixture was filtered through Celite and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (26 mg) as colorless oil. [MS (ESI) m/z 336.2 (M+H)+]
  • 10
  • 2-chloro-4-(pyrimidin-5-yl)-5,6,7,8-tetrahydroquinoline [ No CAS ]
  • [ 315180-17-7 ]
  • 2-[(6-fluoropyridin-2-yl)methoxy]-4-(pyrimidin-5-yl)-5,6,7,8-tetrahydroquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
59 mg With 4,5-bis-(di-tert-butyl-phosphanyl)-9,9-dimethyl-9H-xanthene; tris(dibenzylideneacetone)dipalladium(0) chloroform complex; caesium carbonate; In toluene; at 100℃; for 14h;Inert atmosphere; [Step 2] Production of 2-[(6-fluoropyridin-2-yl)methoxy]-4-(pyrimidin-5-yl )-5,6,7,8-tetrahydroquinoline To 2-chloro-4-(pyrimidin-5-yl)-5,6,7,8-tetrahydroquino line (71 mg), <strong>[315180-17-7](6-fluoropyridin-2-yl)methanol</strong> (41 mg), Pd2(dba)3·CHCl3 (20 mg), t-Bu-X-Phos (33 mg) and cesium carbonate (315 mg) was added toluene (2.9 mL), and the mixture was degassed, then stirred under Ar atmosphere at 100C for 14 hours. After the reaction mixture was allowed to return to room temperature, diluted with ethyl acetate, filtered through Celite, and the filtrate was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (59 mg) as a pale yellow powder. [MS (ESI) m/z 337.3 (M+H)+]
  • 11
  • 2-chloro-4-(pyrimidin-5-yl)-5,6,7,8-tetrahydroquinoline [ No CAS ]
  • [ 315180-17-7 ]
  • 6-([4-(pyrimidin-5-yl)-5,6,7,8-tetrahydroquinolin-2-yl]oxy}methyl)pyridin-2-amine [ No CAS ]
  • 12
  • 2-chloro-4-(2-methylpyrimidin-5-yl)-6,7-dihydro-5H-cyclopenta[b]pyridine [ No CAS ]
  • [ 315180-17-7 ]
  • 2-[(6-fluoropyridin-2-yl)methoxy]-4-(2-methylpyrimidin-5-yl)-6,7-dihydro-5H-cyclopenta[b]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
22 mg With 4,5-bis-(di-tert-butyl-phosphanyl)-9,9-dimethyl-9H-xanthene; tris(dibenzylideneacetone)dipalladium(0) chloroform complex; sodium t-butanolate; In toluene; at 100℃; for 4h;Molecular sieve; Inert atmosphere; Example 39 2-[(6-Fluoropyridin-2-yl)methoxy]-4-(2-methylpyrimi din-5-yl)-6,7-dihydro-5H-cyclopenta[b]pyridine To 2-chloro-4-(2-methylpyrimidin-5-yl)-6,7-dihydro-5H-cyclopenta[b]pyridine (100 mg), <strong>[315180-17-7](6-fluoropyridin-2-yl)methanol</strong> (62 mg), t-Bu-X-Phos (41 mg), NaO-t-Bu (78 mg), Pd2(dba)3·CHCl3 (25 mg) and MS4A was added toluene (2 mL), and the mixture was degassed, then stirred under Ar atmosphere at 100C for 4 hours. After the reaction mixture was allowed to return to room temperature, diluted with ethyl acetate, filtered through Celite, and the filtrate was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (22 mg) as a white powder. [MS (ESI) m/z 337.4 (M+H)+]
  • 13
  • 2-chloro-4-(2-fluoropyridin-3-yl)-5,6,7,8-tetrahydroquinoline [ No CAS ]
  • [ 315180-17-7 ]
  • 4-(2-fluoropyridin-3-yl)-2-[(6-fluoropyridin-2-yl)methoxy]-5,6,7,8-tetrahydroquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 4,5-bis-(di-tert-butyl-phosphanyl)-9,9-dimethyl-9H-xanthene; tris(dibenzylideneacetone)dipalladium(0) chloroform complex; caesium carbonate; In toluene; at 100℃; for 4h;Inert atmosphere; [Step 3] Production of 4-(2-fluoropyridin-3-yl)-2-[(6-fluoropyridin-2-yl)m ethoxy]-5,6,7,8-tetrahydroquinoline To 2-chloro-4-(2-fluoropyridin-3-yl)-5,6,7,8-tetrahydr oquinoline (62 mg), <strong>[315180-17-7](6-fluoropyridin-2-yl)methanol</strong> (36 mg), Pd2(dba)3·CHCl3 (15 mg), t-Bu-X-Phos (24 mg) and cesium carbonate (231 mg) was added toluene (2.6 mL), and the mixture was degassed, then stirred under Ar atmosphere at 100C for 4 hours. After the reaction mixture was allowed to return to room temperature, diluted with ethyl acetate, filtered through Celite, and the filtrate was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound as colorless oil. [MS (ESI) m/z 354.4 (M+H)+]
  • 14
  • 5-(2-chloro-5,6,7,8-tetrahydroquinolin-4-yl)pyridine-2-carbonitrile [ No CAS ]
  • [ 315180-17-7 ]
  • 5-{2-[(6-fluoropyridin-2-yl)methoxy]-5,6,7,8-tetrahydroquinolin-4-yl}pyridine-2-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
57 mg With 4,5-bis-(di-tert-butyl-phosphanyl)-9,9-dimethyl-9H-xanthene; tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; In toluene; at 100℃; for 8h;Inert atmosphere; [Step 2] Production of 5-{2-[(6-fluoropyridin-2-yl)methoxy]-5,6,7,8-tetrah ydroquinolin-4-yl}pyridine-2-carbonitrile To 5-(2-chloro-5,6,7,8-tetrahydroquinolin-4-yl)pyridin e-2-carbonitrile (90 mg), <strong>[315180-17-7](6-fluoropyridin-2-yl)methanol</strong> (55 mg), Pd2(dba)3 (31 mg), t-Bu-X-Phos (28 mg) and cesium carbonate (218 mg) was added toluene (3 mL) and the mixture was degassed, then stirred under Ar atmosphere at 100C for 8 hours. After the reaction mixture was allowed to return to room temperature, diluted with ethyl acetate, filtered through Celite, and the filtrate was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (57 mg) as a white powder. [MS (ESI) m/z 361.3 (M+H)+]
  • 15
  • [ 315180-17-7 ]
  • N-[1-(fluoromethyl)cyclopropyl]-1-[(6-fluoro-2-pyridyl)methyl]-3-[(1-methylpyrazol-4-yl)methyl]-2,4-dioxoquinazoline-6-sulfonamide [ No CAS ]
  • 16
  • [ 124-63-0 ]
  • [ 315180-17-7 ]
  • C7H8FNO3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at 0 - 20℃; The mesylate of <strong>[315180-17-7](6-fluoropyridin-2-yl)methanol</strong> (100 mg) was prepared by reaction with methanesulfonyl chloride (1 .1 eq) and triethylamine (2 eq) in DCM at 0 C, with warming to ambient temperature. N-[1 -(Fluoromethyl)cyclopropyl]-3-[(1 -methylpyrazol-4- yl)methyl]-2,4-dioxo-1 1H-quinazoline-6-sulfonamide (100 mg, 0.260 mmol), the crude mesylate (55 mg, 0.286 mmol) and potassium carbonate (43 mg, 0.312 mmol) in DMF was conventionally heated to 70 C for 4 h. Usual work-up afforded the desired product (26 mg, 0.050 mmol, 19%) as a white powder
 

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