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Chemical Structure| 478148-60-6 Chemical Structure| 478148-60-6
Chemical Structure| 478148-60-6

Furo[2,3-c]pyridin-5-ylmethanol

CAS No.: 478148-60-6

4.5 *For Research Use Only !

Cat. No.: A126154 Purity: 97%

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Product Details of [ 478148-60-6 ]

CAS No. :478148-60-6
Formula : C8H7NO2
M.W : 149.15
SMILES Code : OCC1=CC2=C(OC=C2)C=N1
MDL No. :MFCD11109707
InChI Key :UUKNFBHTKFKPEH-UHFFFAOYSA-N
Pubchem ID :22047174

Safety of [ 478148-60-6 ]

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

Computational Chemistry of [ 478148-60-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 9
Fraction Csp3 0.12
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 40.14
TPSA ?

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

46.26 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.66
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

0.4
Log Po/w (WLOGP)?

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

1.17
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.

-0.24
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

1.74
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.95

Water Solubility

Log S (ESOL):?

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

-1.56
Solubility 4.14 mg/ml ; 0.0278 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.

-0.94
Solubility 17.2 mg/ml ; 0.115 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

-2.72
Solubility 0.282 mg/ml ; 0.00189 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.

-6.93 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)

2.25

Application In Synthesis of [ 478148-60-6 ]

* 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 [ 478148-60-6 ]
  • Downstream synthetic route of [ 478148-60-6 ]

[ 478148-60-6 ] Synthesis Path-Upstream   1~13

  • 1
  • [ 478148-59-3 ]
  • [ 478148-60-6 ]
YieldReaction ConditionsOperation in experiment
90% With sodium hydroxide In methanol; water C14 (770 mg, 3.48 mmol) is dissolved in 10 mL MeOH. 2N NaOH (3 mL, 6 mmol) is added, and the reaction is stirred for 1.5 h at rt.
The solution is concentrated in vacuo to a residue.
Water (20 mL) is added to the residue and extracted with 4*10 mL CH2Cl2.
The combined organic layer is dried over K2CO3, filtered, and then concentrated in vacuo to afford furo[2,3-c]pyridin-5-yl methanol (C16) as a white solid (90percent yield).
Analysis calculated for C8H7NO2: C, 64.42; H, 4.73; N, 9.39. Found: C, 64.60; H. 4.56; N, 9.44.
90% With sodium hydroxide In methanol; water at 20℃; for 1.5 h; C6 (770 mg, 3.48 mmol) is dissolved in 10 mL MEOH. 2N NAOH (3 mL, 6 mmol) is added, and the reaction is stirred for 1.5 h at rt. The solution is concentrated in vacuo to a residue. Water (20 mL) is added to the residue and extracted with 4 x 10 mL CH2C12. The combined organic layer is dried (K2CO3), filtered, and then concentrated in vacuo to afford furo [2,3-c] PYRIDIN-5-YL methanol (2 AS A WHITE SOLID (90percent yield). Analysis calculated for CSH7NO2 : C, 64.42 ; H, 4.73 ; N, 9.39. Found: C, 64.60 ; H, 4.56 ; N, 9.44.
References: [1] Patent: US2003/45540, 2003, A1, .
[2] Patent: WO2004/52894, 2004, A1, . Location in patent: Page 34.
  • 2
  • [ 208519-39-5 ]
  • [ 478148-60-6 ]
YieldReaction ConditionsOperation in experiment
75% With hydrogenchloride; zinc In ethanol; water at 70℃; for 1 h; Heating / reflux C4 (32.0 g, 174 mmol) is combined with zinc powder (34.2 g, 523 mmol) in absolute EtOH (900 mL), using an overhead stirrer. The mixture is heated to 70°C, HC1 (87.2 mL, 1.05 mol) is added slowly drop-wise, and the mixture is heated to reflux for 1 h. The mixture is cooled slightly, filtered to remove the metallic zinc and concentrated to near-dryness. The yellow oil is diluted with H20 (150 mL) and EtOAc (950 mL) and is treated slowly drop-wise with 20percent Na2C03 (310 mL) as the mixture is warmed to reflux. The vigorously stirred (using overhead stirrer) mixture is refluxed for 1 h, cooled slightly and the organics removed via cannula under reduced pressure. Additional EtOAc (600 mL) is added, the mixture is heated to reflux for 1 h, cooled slightly and the organics removed as above. More EtOAc (600 mL) is added, the mixture is stirred at rt overnight then heated to reflux for 1 h, cooled slightly and most of the organics removed as above. The remaining mixture is filtered through celite, rinsed with EtOAc until no additional product elutes, and the layers separated. The aqueous layer is further extracted with EtOAc (2 X 400 mL). The combined organics are dried (MGS04) and concentrated to a dark yellow solid (23.6 g). The crude material is chromatographed over 900 g slurry-packed silica gel, eluting with 60percent EtOAc/hexane (3 L), 70percent EtOAc/hexane (2 L), and finally 100percent EtOAc. The appropriate fractions are combined and concentrated in vacuo to'afford C7 (19.5 g, 75percent) as a white solid. Anal. Calcd for CgH7NO2 : C, 64.42 ; H, 4.73 ; N, 9. 39 ; Found: C, 64.60 ; H, 4.56 ; N, 9.44.
References: [1] Patent: WO2004/52894, 2004, A1, . Location in patent: Page 35.
[2] Journal of Medicinal Chemistry, 2006, vol. 49, # 14, p. 4425 - 4436.
  • 3
  • [ 478149-20-1 ]
  • [ 478148-60-6 ]
YieldReaction ConditionsOperation in experiment
92% at 20℃; a-8)
Preparation of furo[2,3-c]pyridin-5-yl methanol
Furo[2,3-c]pyridin-5-yl methyl acetate (722 mg, 3.78 mmol) was dissolved in methanol (19 mL), added potassium carbonate (1.04 g, 7.56 mmol) at room temperature, and the mixture was stirred at room temperature overnight.
The reaction solution was added 1N-aqueous solution of hydrochloric acid under ice-cold conditions, and extracted with chloroform.
The organic layer was dried over anhydrous sodium sulfate, and concentrated in vacuo.
The obtained residue was purified by silica-gel column chromatography (hexane/ethyl acetate), and the title compound (521 mg (yield 92percent)) was obtained as a yellow oil.
1H-NMR (CDCl3) δ: 3.68 (1H, s), 4.85 (2H, s), 6.79 (1H, s), 7.54 (1H, s), 7.79 (1H, s), 8.83 (1H, s).
70% With sodium hydroxide In 1,4-dioxane; water (d)
Furo[2,3-c]pyridin-5-ylmethanol
A solution of furo[2,3-c]pyridin-5-ylmethyl acetate (1.15 g) in 1,4-dioxane (30 ml) and water (10 ml) was treated with 2M sodium hydroxide (12 ml) then stirred at ambient temperature for 18hrs.
The mixture was then partitioned between ethyl acetate and water.
The organics were separated and dried then evaporated to dryness.
This gave an oil (0.63 g, 70percent).
MS (+ve ion electrospray) m/z 150 (MH+).
70% With sodium hydroxide; water In 1,4-dioxane at 20℃; for 18 h; (d)
Furo[2,3-c]pyridin-5-ylmethanol
A solution of furo[2,3-c]pyridin-5-ylmethyl acetate (1.15 g) in 1,4-dioxane (30 ml) and water (10 ml) was treated with 2M sodium hydroxide (12 ml) then stirred at ambient temperature for 18 hrs.
The mixture was then partitioned between ethyl acetate and water.
The organics were separated and dried then evaporated to dryness.
This gave an oil (0.63 g, 70percent).
MS (+ve ion electrospray) m/z 150 (MH+).
70% With sodium hydroxide; water In 1,4-dioxane at 20℃; for 18 h; (d) Furo[2,3-c]pyridin-5-ylmethanol; A solution of furo[2,3-clpyridin-5-ylmethyl acetate (1.15 g) in 1 ,4-dioxane(30 ml) and water (10 ml) was treated with 2M sodium hydroxide (12 ml) then stirred at ambient temperature for 18h. The mixture was then partitioned between <n="35"/>ethyl acetate and water. The organic fractions were separated and dried then evaporated to dryness. This gave an oil (0.63 g, 70percent).MS (+ve ion electrospray) m/z 150 (MH+).
70% With sodium hydroxide; water In 1,4-dioxane at 20℃; for 18 h; (d) Furo[2,3-c]pyridin-5-ylmethanol; A solution of furo[2,3-c]pyridin-5-ylmethyl acetate (1.15 g) in 1,4-dioxane (30ml) and water (10ml) was treated with 2M sodium hydroxide (12ml) then stirred at ambient temperature for 18h. The mixture was then partitioned between ethyl acetate and water. The organic fractions were separated and dried then evaporated to dryness. This gave an oil (0.63g, 70percent). MS (+ve ion electrospray) m/z 150 (MH+).
70% With sodium hydroxide; water In 1,4-dioxane at 20℃; for 18 h; (d) Furo [2,3 -c]pyridin-5 -ylmethanol; A solution of furo[2,3-c]pyridin-5-ylmethyl acetate (1.15 g) in 1,4-dioxane (30 ml) and water (10 ml) was treated with 2M sodium hydroxide (12 ml) then stirred at ambient temperature for 18hrs. The mixture was then partitioned between ethyl acetate and water. The organics were separated and dried then evaporated to dryness. This gave an oil (0.63 g, 70percent). MS (+ve ion electrospray) m/z 150 (MH+).

References: [1] Patent: US2010/280013, 2010, A1, . Location in patent: Page/Page column 52-53.
[2] Patent: EP1980251, 2008, A1, .
[3] Patent: US2008/221110, 2008, A1, . Location in patent: Page/Page column 17.
[4] Tetrahedron Letters, 2010, vol. 51, # 38, p. 5038 - 5040.
[5] Patent: WO2007/115947, 2007, A1, . Location in patent: Page/Page column 33-34.
[6] Patent: WO2008/9700, 2008, A1, . Location in patent: Page/Page column 89.
[7] Patent: WO2008/128953, 2008, A1, . Location in patent: Page/Page column 116.
[8] Patent: WO2007/122258, 2007, A1, . Location in patent: Page/Page column 54.
  • 4
  • [ 952587-20-1 ]
  • [ 478148-60-6 ]
  • [ 478149-20-1 ]
YieldReaction ConditionsOperation in experiment
27% for 18 h; Heating / reflux (c) Furo[2,3-clpyridin-5-ylmethyl acetate; {5-Hydroxy-4-[(trimethylsilyl)ethynyl]-2-pyridinyl}methyl acetate, trifluoroacetate) (10 g, 22 mmol) was dissolved in pyridine (200 ml) and treated with copper(l) iodide (5.2 g, 27 mmol) then heated under reflux for 18hrs. The mixture was allowed to cool, evaporated to dryness and the residue partitioned between ethyl acetate and water. This mixture was filtered through kieselguhr to remove copper residues. The organic layer was separated from the filtrate, dried and chromatographed on silica gel, eluting with a gradient of 10 - 60percent ethyl acetate in 40-600C petroleum ether. This gave furo[2,3-c]pyridin-5-ylmethyl acetate (1.15 g, 27percent) and a less polar product [2-(trimethylsilyl)furo[2,3-clpyridin- 5-yl]methyl acetate (1.3 g, 23percent) as oils.MS (+ve ion electrospray) m/z 192 (MH+) and MS (+ve ion electrospray) m/z 264 (MH+).
References: [1] Patent: WO2007/115947, 2007, A1, . Location in patent: Page/Page column 33.
  • 5
  • [ 6636-78-8 ]
  • [ 478148-60-6 ]
References: [1] Journal of Medicinal Chemistry, 2006, vol. 49, # 14, p. 4425 - 4436.
[2] Patent: WO2004/52894, 2004, A1, .
[3] Patent: WO2004/52894, 2004, A1, .
[4] Patent: WO2004/52894, 2004, A1, .
  • 6
  • [ 208519-41-9 ]
  • [ 478148-60-6 ]
References: [1] Journal of Medicinal Chemistry, 2006, vol. 49, # 14, p. 4425 - 4436.
[2] Patent: WO2004/52894, 2004, A1, .
[3] Patent: WO2004/52894, 2004, A1, .
[4] Patent: WO2004/52894, 2004, A1, .
  • 7
  • [ 208519-37-3 ]
  • [ 478148-60-6 ]
References: [1] Journal of Medicinal Chemistry, 2006, vol. 49, # 14, p. 4425 - 4436.
[2] Patent: WO2004/52894, 2004, A1, .
[3] Patent: WO2004/52894, 2004, A1, .
[4] Patent: WO2004/52894, 2004, A1, .
  • 8
  • [ 208519-38-4 ]
  • [ 478148-60-6 ]
References: [1] Journal of Medicinal Chemistry, 2006, vol. 49, # 14, p. 4425 - 4436.
[2] Patent: WO2004/52894, 2004, A1, .
[3] Patent: WO2004/52894, 2004, A1, .
  • 9
  • [ 724788-78-7 ]
  • [ 478148-60-6 ]
References: [1] Patent: WO2008/9700, 2008, A1, .
[2] Patent: WO2008/128953, 2008, A1, .
  • 10
  • [ 952587-18-7 ]
  • [ 478148-60-6 ]
References: [1] Patent: WO2008/9700, 2008, A1, .
[2] Patent: WO2008/128953, 2008, A1, .
  • 11
  • [ 952587-20-1 ]
  • [ 478148-60-6 ]
References: [1] Patent: WO2008/9700, 2008, A1, .
[2] Patent: WO2008/128953, 2008, A1, .
  • 12
  • [ 956010-20-1 ]
  • [ 478148-60-6 ]
References: [1] Patent: WO2007/122258, 2007, A1, . Location in patent: Page/Page column 54.
  • 13
  • [ 441044-90-2 ]
  • [ 478148-60-6 ]
References: [1] Patent: WO2004/52894, 2004, A1, .
 

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