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Structure of 112372-15-3

Chemical Structure| 112372-15-3

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Product Details of [ 112372-15-3 ]

CAS No. :112372-15-3
Formula : C8H5NO3
M.W : 163.13
SMILES Code : O=C(C(O1)=CC2=C1C=NC=C2)O
MDL No. :MFCD11869932
InChI Key :WMPIDXCJMDIDQY-UHFFFAOYSA-N
Pubchem ID :13803072

Safety of [ 112372-15-3 ]

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

Computational Chemistry of [ 112372-15-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 9
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 40.97
TPSA ?

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

63.33 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.04
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

1.11
Log Po/w (WLOGP)?

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

1.53
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.

-0.09
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

1.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.97

Water Solubility

Log S (ESOL):?

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

-2.04
Solubility 1.49 mg/ml ; 0.00913 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.

-2.03
Solubility 1.51 mg/ml ; 0.00927 mol/l
Class?

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

-2.28
Solubility 0.86 mg/ml ; 0.00527 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.

-6.51 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.

0.56

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)

2.36

Application In Synthesis of [ 112372-15-3 ]

* 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 [ 112372-15-3 ]
  • Downstream synthetic route of [ 112372-15-3 ]

[ 112372-15-3 ] Synthesis Path-Upstream   1~11

  • 1
  • [ 138173-83-8 ]
  • [ 112372-15-3 ]
YieldReaction ConditionsOperation in experiment
89%
Stage #1: With water; potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 16 h;
Stage #2: With acetic acid In tetrahydrofuran; methanol
b: furo[2,3-clpyridine-2-carboxylic acid:To a solution of ethyl furo[2,3-c]pyridine-2-carboxylate (3.82 g, 19.98 mmol) in water:THF:MeOH (1 : 1 : 1 , 60 mL) was added potassium hydroxide (3.36 g, 59.9 mmol) and the resulting mixture was stirred at ambient temperature for 16 hours. The solvent volume was then reduced to ~20 mL and acetic acid was added until pH ~4. The solids were collected by vacuum filtration, washed twice with water, and dried in a vacuum oven overnight to afford the title compound (2.90 g, 89percent). 1H NMR (DMSO-de): δ 9.09 (s, 1H), 8.47 (d, 1H), 7.81 (dd, 1H), 7.71 (d, 1H), 3.36 (br s, 1H).
75% With water; potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 16 h; Step 6. To a solution of ethyl furo[2,3-c]pyridine-2-carboxylate (158 g, 0.83 mol) in water:THF:MeOH (1:1:1, 2.4 L) was added KOH (139 g, 2.49 mol). Thereaction mixture was stirred at rt for 16 h and then concentrated to a volume of 750 mL. To this residue was added acetic acid until pH 4. The resulting solids were collected by filtration, washed with water (300 mLx2) and dried in a vacuum oven overnight to give the title compound (101 g, 75percent) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) 6 9.07 (s, 1H), 8,47 (d, J 5.6 Hz, 1H), 7.80 (d, J = 5.2 Hz,1H), 7.61 (s, 1H). MS (ESI+) m/z: 164 [M+F]+
75% With water; potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 16 h; Step 6. To a solution of ethyl furo[2,3-cjpyridine-2-carboxylate (158 g, 0.83 mol) in water:THF:MeOH (I: 1:1, 2.4 L) was added KOH (139 g, 2.49 mol). Thereaction mixture was stirred at ii for 1 6 h and then concentrated to a volume of 750 mL. To this residue was added acetic acid until pH 4. The resulting solids were collected by filtration, washed with water (300 mLx2) and dried in a vacuum oven overnight to give the title compound (101 g, 75percent) as a pale yellow solid. 1H NMR (400 Mi-Iz, DMSO-d6) 6 9.07 (s, In), 8,47 (d, J 5.6 Hz, I H), 7.80 (d, J = 5.2 Hz,1H), 7.61 (s, IH). MS (ES1-b) ni z: 164 [M+F]+
75% With water; potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 16 h; Step 6. To a solution of ethyl furo[2,3-c]pyridine-2-carboxylate ( 158 g, 0,83 mol) in water:THF:MeOH (1 : 1 : 1 , 2 4 L) was added KOH ( 139 g, 2.49 mol). The reaction mixture was stirred at rt for 1 6 h and then concentrated to a volume of 750 mL. To this residue was added acetic acid until pH ~ 4. The resulting solids were collected by filtration, washed with water (300 mL> 2) and dried in a vacuum oven overnight to give the title compound ( 101 g, 75percent) as a pale yellow solid. NMR (400 MHz, DMSO-ay δ 9.07 (s, 1 H), 8.47 (d, = 5.6 Hz, 1 H), 7.80 (d, J = 5.2 Hz, 1 H), 7.61 (s, 1 H). MS (ESI+) m. z: 1 64 [M+H] \
75% With water; potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 16 h; Step 6. To a solution of ethyl furo[2,3-c]pyridine-2-carboxylate (158 g, 0.83 mol) in water:THF:MeOH (1:1:1, 2.4 L) was added KOH (139 g, 2.49 mol). Thereaction mixture was stirred at rt for 16 h and then concentrated to a volume of 750 mL. To this residue was added acetic acid until pH 4. The resulting solids were collected by filtration, washed with water (300 mLx2) and dried in a vacuum oven overnight to give the title compound (101 g, 75percent) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) 6 9.07 (s, 1H), 8,47 (d, J 5.6 Hz, 1H), 7.80 (d, J = 5.2 Hz,1H), 7.61 (s, 1H). MS (ESI+) m/z: 164 [M+F]+
75% With water; potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 16 h; Intermediate 1: Furo[2,3-clpyridine-2-carboxylic acid [0171] Step 6. To a solution of ethyl furo[2,3-c]pyridine-2-carboxylate (158 g, 0.83 mol) in water:THF:MeOH (1:1:1, 2.4 L) was added KOH (139 g, 2.49 mol). The reaction mixture was stirred at rt for 16 h and then concentrated to a volume of 750 mL. To this residue was added acetic acid until pH 4. The resulting solids were collected by filtration, washed withwater (300 mLx2) and dried in a vacuum oven overnight to give the title compound (101 g, 75percent) as a pale yellow solid. ‘H NMR (400 MHz, DMSO-d6) ö 9.07 (s, 1H), 8.47 (d, J = 5.6 Hz, 1H), 7.80 (d, J = 5.2 Hz, 1H), 7.61 (s, 1H). MS (ESI+) m/z: 164 [M+Hf’.
75% With water; potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 16 h; Step 6. To a solution of ethyl furo[2,3-c]pyridine-2-carboxylate (158 g, 0.83 mol) in water:THF:MeOH (1 : 1 : 1, 2.4 L) was added KOH (139 g, 2.49 mol). The reaction mixture was stirred at rt for 16 h and then concentrated to a volume of 750 mL. To this residue was added acetic acid until pH ~ 4. The resulting solids were collected by filtration, washed with water (300 mLx2) and dried in a vacuum oven overnight to give the title compound (101 g, 75percent) as a pale yellow solid. 1H NMR (400 MHz, DMSO-J6) δ 9.07 (s, 1H), 8.47 (d, J = 5.6 Hz, 1H), 7.80 (d, J = 5.2 Hz, 1H), 7.61 (s, 1H). MS (ESI+) m/z: 164 [M+H]+.

References: [1] Patent: WO2012/31197, 2012, A1, . Location in patent: Page/Page column 400-401.
[2] Patent: WO2013/127266, 2013, A1, . Location in patent: Page/Page column 128; 129; 130.
[3] Patent: WO2013/127267, 2013, A1, . Location in patent: Page/Page column 79; 81.
[4] Patent: WO2013/127269, 2013, A1, . Location in patent: Page/Page column 143.
[5] Patent: WO2013/127268, 2013, A1, . Location in patent: Page/Page column 57; 59.
[6] Patent: WO2013/130935, 2013, A1, . Location in patent: Paragraph 0171.
[7] Patent: WO2013/130943, 2013, A1, . Location in patent: Paragraph 0179.
  • 2
  • [ 112372-06-2 ]
  • [ 112372-15-3 ]
YieldReaction ConditionsOperation in experiment
84% With potassium dihydrogenphosphate; NaClO2 In tetrahydrofuran; water; <i>tert</i>-butyl alcohol C33 (558 mg, 3.79 mmol) is dissolved in 25 mL THF, 12 mL t-butanol, and 12 mL water. KH2PO4 (1.03 g, 7.6 mmol) and NaClO2 (1.28 g, 114 mmol) are added, and the reaction is stirred 3 h at rt.
The reaction is concentrated in vacuo to a residue.
Water (20 mL) is added, and the pH of the mixture is adjusted to 3 with 10percent aqueous HCl.
The mixture is stirred 20 min in an ice bath, the resultant white solid is collected, washed with water and dried to afford furo[2,3-c]pyridine-2-carboxylic acid (C34) (84percent yield). HRMS (FAB) calculated for C8H5NO3+H: 164.0348, found 164.0344 (M+H)+.
References: [1] Patent: US2003/45540, 2003, A1, .
  • 3
  • [ 927804-63-5 ]
  • [ 112372-15-3 ]
References: [1] Patent: WO2012/31197, 2012, A1, .
[2] Patent: WO2013/127266, 2013, A1, .
[3] Patent: WO2013/127267, 2013, A1, .
[4] Patent: WO2013/127269, 2013, A1, .
[5] Patent: WO2013/127268, 2013, A1, .
[6] Patent: WO2013/130935, 2013, A1, .
[7] Patent: WO2013/130943, 2013, A1, .
  • 4
  • [ 112372-12-0 ]
  • [ 112372-15-3 ]
References: [1] Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 373 - 376.
  • 5
  • [ 18343-02-7 ]
  • [ 112372-15-3 ]
References: [1] Patent: WO2013/127266, 2013, A1, .
[2] Patent: WO2013/127267, 2013, A1, .
[3] Patent: WO2013/127269, 2013, A1, .
[4] Patent: WO2013/127268, 2013, A1, .
[5] Patent: WO2013/130935, 2013, A1, .
[6] Patent: WO2013/130943, 2013, A1, .
  • 6
  • [ 106531-50-4 ]
  • [ 112372-15-3 ]
References: [1] Patent: WO2013/127266, 2013, A1, .
[2] Patent: WO2013/127267, 2013, A1, .
[3] Patent: WO2013/127269, 2013, A1, .
[4] Patent: WO2013/127268, 2013, A1, .
[5] Patent: WO2013/130935, 2013, A1, .
[6] Patent: WO2013/130943, 2013, A1, .
  • 7
  • [ 10128-71-9 ]
  • [ 112372-15-3 ]
References: [1] Patent: WO2013/127266, 2013, A1, .
[2] Patent: WO2013/127267, 2013, A1, .
[3] Patent: WO2013/127268, 2013, A1, .
[4] Patent: WO2013/130943, 2013, A1, .
  • 8
  • [ 18342-97-7 ]
  • [ 112372-15-3 ]
References: [1] Patent: WO2013/127266, 2013, A1, .
[2] Patent: WO2013/127267, 2013, A1, .
[3] Patent: WO2013/127268, 2013, A1, .
[4] Patent: WO2013/130943, 2013, A1, .
  • 9
  • [ 112372-06-2 ]
  • [ 112372-15-3 ]
References: [1] Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 373 - 376.
  • 10
  • [ 19539-50-5 ]
  • [ 112372-15-3 ]
References: [1] Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 373 - 376.
  • 11
  • [ 112372-09-5 ]
  • [ 112372-15-3 ]
References: [1] Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 373 - 376.
 

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