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Chemical Structure| 13472-83-8 Chemical Structure| 13472-83-8

Structure of 13472-83-8

Chemical Structure| 13472-83-8

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Product Details of [ 13472-83-8 ]

CAS No. :13472-83-8
Formula : C6H7NO2
M.W : 125.13
SMILES Code : OC1=CC=CN=C1OC
MDL No. :MFCD00457990
InChI Key :RDBZAWZPZSBYDA-UHFFFAOYSA-N
Pubchem ID :747009

Safety of [ 13472-83-8 ]

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

Computational Chemistry of [ 13472-83-8 ] 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 32.75
TPSA ?

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

42.35 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.59
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

0.8
Log Po/w (WLOGP)?

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

0.8
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.

-0.07
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

0.88
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.8

Water Solubility

Log S (ESOL):?

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

-1.55
Solubility 3.55 mg/ml ; 0.0284 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.27
Solubility 6.71 mg/ml ; 0.0536 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

-1.53
Solubility 3.66 mg/ml ; 0.0292 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.

-6.5 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)

1.59

Application In Synthesis of [ 13472-83-8 ]

* 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 [ 13472-83-8 ]

[ 13472-83-8 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 40263-57-8 ]
  • [ 124-41-4 ]
  • [ 13472-83-8 ]
  • 2
  • [ 13472-83-8 ]
  • [ 79-44-7 ]
  • dimethyl-carbamic acid-(2-methoxy-[3]pyridyl ester) [ No CAS ]
  • 3
  • [ 13472-83-8 ]
  • [ 74-88-4 ]
  • 1-methyl-1,4-dihydro-pyridine-2,3-dione [ No CAS ]
  • 4
  • [ 13472-83-8 ]
  • [ 74-88-4 ]
  • [ 19365-01-6 ]
  • 5
  • [ 13472-83-8 ]
  • [ 16867-04-2 ]
  • 8
  • diazotized. 2-methoxy-<3>pyridylamine [ No CAS ]
  • [ 13472-83-8 ]
  • 9
  • [ 13472-83-8 ]
  • [ 106-89-8 ]
  • [ 70637-88-6 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In acetonitrile; The starting material can be obtained as follows: A mixture of 15.4 g of <strong>[13472-83-8]3-hydroxy-2-methoxy-pyridine</strong>, 16 g of potassium carbonate, 25 ml of epichlorohydrin and 150 ml of acetonitrile is refluxed for 7 hours. Cooling and filtering the mixture and evaporating the filtrate yields crude 3-(2,3-epoxy-propoxy)-2-methoxypyridine, which is used without further purification. In an analogous manner, 1-{1-[2-hydroxy-3-(2-methoxy-6-methyl-3-pyridyloxy)-propyl]-4-piperidyl}-imidazolidin-2-one, which after recrystallisation from a mixture of methylene chloride and diethyl ether melts at 144-147, can be obtained by reacting 20 g of crude 3-(2,3-epoxy-propoxy)-2-methoxy-6-methyl-pyridine and 16.5 g of 1-(4-piperidyl)-imidazolidin-2-one.
  • 10
  • [ 13472-83-8 ]
  • [ 76470-38-7 ]
  • 11
  • [ 13472-83-8 ]
  • [ 128796-39-4 ]
  • [ 924312-04-9 ]
YieldReaction ConditionsOperation in experiment
63% With triethylamine;copper diacetate; In dichloromethane; at 20℃; for 48.0h;Molecular sieve; (1) Production of 2-methoxy-3-[4-(trifluoromethyl)phenoxy]pyridine: [4-(Trifluoromethyl)phenyl]boronic acid (668 mg, 3.52 mmol), copper(II) acetate (480 mg, 2.64 mmol), triethylamine (0.74 mL, 5.28 mmol) and Molecular Sieve 4A (1.76 g) were added to a methylene chloride solution (20 mL) of <strong>[13472-83-8]2-methoxypyridin-3-ol</strong> (220 mg, 1.76 mmol), and stirred at room temperature for 2 days. The reaction liquid was filtered through Celite, then aqueous saturated sodium hydrogencarbonate solution was added to the filtrate, and extracted with ethyl acetate. The obtained organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered. The obtained filtrate was concentrated under reduced pressure, then the residue was purified by silica gel column chromatography (hexane:ethyl acetate = 10:0 to 9:1) to obtain the entitled compound (298 mg, 63 %). Mass Spectrum (ESI): 270.0 (M+H).
  • 12
  • [ 13472-83-8 ]
  • C6H4BrNO [ No CAS ]
  • 13
  • [ 13472-83-8 ]
  • 5-bromo-3-methoxy-11-oxa-4-aza-tricyclo[6.2.1.02,7]undeca-2(7),3,5,9-tetraene [ No CAS ]
  • 14
  • [ 13472-83-8 ]
  • [ 934965-64-7 ]
  • 15
  • [ 13472-83-8 ]
  • 1-(2-methoxypyridin-3-yloxy)-3-(4-phenylpiperazin-1-yl)propan-2-ol [ No CAS ]
  • 16
  • [ 109-00-2 ]
  • [ 13472-83-8 ]
  • 17
  • [ 13472-83-8 ]
  • [ 344420-23-1 ]
  • [ 497866-25-8 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In DMF (N,N-dimethyl-formamide); for 6.0h;Heating / reflux; To a mixture of 10 g of 3-(2,5-difluoro-4-nitrophenyl)-1-methyl-6-triffuoromethyl-1H-pyrimidin-2,4-dione, 5.0 g of <strong>[13472-83-8]3-hydroxy-2-methoxypyridine</strong> and 100 ml of N,N-dimethylformamide, 7.8 g of potassium carbonate were added and refluxed for 6 hours under stirring. Then, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with aqueous sodium bicarbonate and saturated brine subsequently, dried over magnesium sulfate and concentrated to give 12.8 g of 3-[4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-2-nitro-1,2,3,6-tetrahydropyrimidin-1-yl)phenoxy]-2-methoxypyridine.1H-NMR (300M Hz, CDCl3, TMS delta (ppm)): 3.52 (3H, q, J=1.2 Hz), 3.93 (3H, s), 6.32 (1H, s), 6.76 (1H, d, J=5.8 Hz), 6.93 (1H, dd, J=5.0 Hz, 7.8 Hz), 7.40 (1H, dd, J=1.4 Hz, 7.8 Hz), 7.90 (1H, d, J=8.6 Hz), 8.04 (1H, dd, J=1.4 Hz, 5.0 Hz)
With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 2.0h; Step A: Preparation of 3-[2-fluoro-5-[(2-methoxy-3-pyridinyl)oxy]-4-nitrophenyl]-l- methyl-6-(trifluoromethyl)-2,4(lH,3H)-pyrimidinedioneA mixture of 3-(2,5-difiuoro-4-nitrophenyl)-l-methyl-6-(trifluoromethyl)-2,4(lH,3H)- pyrimidinedione (2.25 g, 6.4 mmol) (prepared as described in WO 02/098227), 2-methoxy- 3-pyridinol (800 mg, 6.4 mmol) and potassium carbonate (1.06 g, 7.68 mmol) in N,N- dimethylformamide (15 mL) was heated to 70 C for 2 h, then allowed to cool. The resulting reaction mixture was filtered and the potassium carbonate was washed with ethyl acetate. The combined filtrates were concentrated in vacuo and the resulting residue was subjected to silica gel column chromatography eluting with ethyl acetate in hexanes to give the title compound as a light brown solid (2.82 g).in NMR delta 7.90 (d, 1H), 7.40 (m, 1H), 6.93 (m, 2H), 6.76 (m, 1H), 6.32 (s, 1H), 3.92 (s, 3H), 3.53 (s, 3H).
  • 18
  • [ 13472-83-8 ]
  • [ 497866-09-8 ]
  • 19
  • [ 13472-83-8 ]
  • [ 497866-27-0 ]
  • 20
  • [ 13472-83-8 ]
  • [ 497866-29-2 ]
  • 21
  • [ 13472-83-8 ]
  • [ 1344992-32-0 ]
  • 3-[2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluorophenoxy]-2-hydroxy-α-methoxy-1(2H)-pyridineacetic acid [ No CAS ]
  • 22
  • [ 13472-83-8 ]
  • [ 6216-63-3 ]
  • (S)-N-Cbz-2-(2-methoxy-3-pyridyloxymethyl)pyrrolidine [ No CAS ]
  • 23
  • [ 13472-83-8 ]
  • (S)-N-methyl-2-((2-methoxy-3-pyridyl)oxymethyl)pyrrolidine [ No CAS ]
  • 24
  • [ 13472-83-8 ]
  • (S)-2-((2-methoxy-3-pyridyl)oxymethyl)pyrrolidine [ No CAS ]
  • 25
  • [ 163105-90-6 ]
  • [ 13472-83-8 ]
  • 26
  • [ 13472-83-8 ]
  • 4-(chloromethyl)-1-(3-(1,1-difluoroethyl)-4-fluorophenyl)-1H-1,2,3-triazole [ No CAS ]
  • 5-chloro-N-[[1-[3-(difluoromethyl)phenyl]triazol-4-yl]methyl]pyrimidin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; General procedure: To a solution of 4-(chloromethyl)-i -(3-(difluoromethyl)phenyl)-i H-i 2,3-triazole (25 mg, 0.103 mmol) and 2-amino-5-chloropyrimidine (17 mg, 0.13mmol) in DMF (1.5 mL) was added K2003 (57 mg, 0.41 mmol). The resultingmixture was stirred at 100 C for 72 h. The reaction mixture was diluted withwater (8 mL) and extracted with EtOAc (3 x 10 mL). The combined organicswere dried over Na2504, filtered, and concentrated under reduced pressure.Purification (FCC, 5i02, 0-80% EtOAc/hexanes) afforded the title compound(6.2 mg, 18%).
  • 27
  • [ 13472-83-8 ]
  • 4-nitrophenyl (S)-4-((4-chlorobenzamido)(phenyl)methyl)piperidine-1-carboxylate [ No CAS ]
  • 2-methoxypyridin-3-yl 4-[(S)-[(4-chlorophenyl)formamido](phenyl)methyl]piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With caesium carbonate; In dimethyl sulfoxide; at 140℃; for 1.0h;Microwave irradiation; A mixture of 4-nitrophenyl (S)-4-((4-chlorobenzamido)(phenyl)methyl)piperidine-1 - carboxylate (100 mg, 0.20 mmol), <strong>[13472-83-8]2-methoxypyridin-3-ol</strong> (100 mg, 0.80 mmol), Cs2C03(130 mg, 0.40 mmol) and DMSO (2.5 mL) was heated to 140C by microwave. After stirred at this temperature for 1 h, the reaction mixture was partitioned between EtOAc/H20, and the layers were separated. The organic layer was washed with brine and dried over Na2S04. Solvent was removed under vacuum and the residue was purified by Gilson (C18, 10-50% MeCN in water with 0.1 % formic acid) to afford the title compound (78 mg, 81 %) as a white solid.1H NMR (400 MHz, DMSO) delta 8.90 (d, J = 8.6 Hz, 1 H), 8.01 (d, J = 3.6 Hz, 1 H), 7.89 (d, J = 8.5 Hz, 2H), 7.61 - 7.48 (m, 3H), 7.47 - 7.40 (m, 2H), 7.34 (t, J = 7.5 Hz, 2H), 7.28 - 7.22 (m, 1 H), 7.03 - 6.97 (m, 1 H), 4.81 (t, J = 9.2 Hz, 1 H), 4.20 - 3.93 (m, 2H), 3.85 (s, 3H), 3.00 - 2.78 (m, 2H), 2.13 - 1 .95 (m, 2H), 1 .34 - 1 .13 (m, 3H). LCMS (ESI) m/z calcd for C26H26CIN3O4: 479.16. Found: 480.28/482.23 (M/M+2)+.
  • 28
  • [ 13472-83-8 ]
  • [ 1217800-70-8 ]
  • 4,5-dichloro-2-[(2-methoxy-3-pyridyl)oxy]benzaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With caesium carbonate; In N,N-dimethyl-formamide; at 75℃; for 0.166667h; A mixture of 4,5-dichloro-2-fluoro-benzaldehyde (502 mg, 2.60 mmol), 2-methoxypyridin-3- ol (325 mg, 2.60 mmol) and cesium carbonate (1.02 g, 3.12 mmol) in DMF (4 mL) was heated at 75 C for 10 minutes. The cooled reaction mixture was diluted with ethyl acetate (50 mL) then partitioned with water (50 mL). The aqueous portion was extracted with ethyl acetate (2 x 25 mL) and the combined organics were washed with saturated sodium chloride solution (2 x 25 mL), dried over sodium sulfate concentrated in vacuo. The product was purified by silica gel chromatography (0-100% ethyl acetate/hexanes) to provide 4,5-dichloro-2-[(2-methoxy-3-pyridyl)oxy]benzaldehyde (650 mg, 84%). ESI-MS m/z calc. 297.00, found 298.1 (M+l)+; Retention time (Method A): 0.68 minutes (1 minutes run). 1H NMR (400 MHz, DMSO-d6) 5 10.35 (s, 1H), 8.12 (dd, J = 5.0, 1.6 Hz, 1H), 7.97 (s, 1H), 7.70 (dd, J = 7.7, 1.6 Hz, 1H), 7.14 - 7.08 (m, 2H), 3.87 (s, 3H) ppm
  • 29
  • [ 13472-83-8 ]
  • 4,5-dichloro-2-[(2-methoxy-3-pyridyl)oxy]benzoic acid [ No CAS ]
  • 30
  • [ 13472-83-8 ]
  • 4,5-dichloro-2-[(2-methoxy-3-pyridyl)oxy]benzoyl chloride [ No CAS ]
  • 31
  • [ 13472-83-8 ]
  • N-(3-carbamoyl-4-fluorophenyl)-4,5-dichloro-2-[(2-methoxy-3-pyridyl)oxy]benzamide [ No CAS ]
  • 32
  • [ 13472-83-8 ]
  • [ 299176-17-3 ]
  • C18H21N3O6 [ No CAS ]
  • 33
  • [ 13472-83-8 ]
  • C18H23N3O4 [ No CAS ]
  • 34
  • [ 13472-83-8 ]
  • C28H31N3O8 [ No CAS ]
  • 35
  • [ 13472-83-8 ]
  • C23H21N3O5 [ No CAS ]
 

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