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Chemical Structure| 697739-12-1 Chemical Structure| 697739-12-1

Structure of 697739-12-1

Chemical Structure| 697739-12-1

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Product Details of [ 697739-12-1 ]

CAS No. :697739-12-1
Formula : C10H10N2O2
M.W : 190.20
SMILES Code : CCOC(=O)C1=CC=CN2C=NC=C12
MDL No. :MFCD20921983
InChI Key :IZZCPMXJHNYFKD-UHFFFAOYSA-N
Pubchem ID :69160068

Safety of [ 697739-12-1 ]

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

Computational Chemistry of [ 697739-12-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 9
Fraction Csp3 0.2
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 51.28
TPSA ?

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

43.6 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.2
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

2.07
Log Po/w (WLOGP)?

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

1.51
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.

0.94
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

1.09
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.56

Water Solubility

Log S (ESOL):?

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

-2.6
Solubility 0.477 mg/ml ; 0.00251 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.

-2.61
Solubility 0.462 mg/ml ; 0.00243 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

-2.57
Solubility 0.513 mg/ml ; 0.0027 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.

-5.99 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)

1.79

Application In Synthesis of [ 697739-12-1 ]

* 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 [ 697739-12-1 ]

[ 697739-12-1 ] Synthesis Path-Downstream   1~15

  • 1
  • [ 64-18-6 ]
  • [ 697739-11-0 ]
  • [ 697739-12-1 ]
YieldReaction ConditionsOperation in experiment
[0143] A mixture of 44.8 mL of acetic anhydride and 19.2 mL of formic acid was heated in a 50-60 C oil bath temperature for 3 h and then cooled to rt to give formic-acetic anhydride, which was then slowly added to the solid ethyl 2-(aminomethyl)-3-pyridinecarboxylate HCl and then stirred at rt for 8 h. Excess reagent was evaporated to give a residue, which was neutralized by very slow addition of sat. NaHC03 solution. Solution was extracted with DCM, dried and evaporated to provide ethyl imidazo[l,5-a]pyridine-8-carboxylate as a yellow solid (crude weight 2.7 g). MS: exact mass calculated for C10H10N2O2, 190.07; m/z found, 191 [M+H] +.
A mixture of 44.8 mL of acetic anhydride and 19.2 mL of formic acid was heated in a 50-60 C. oil bath temperature for 3 h and then cooled to rt to give formic-acetic anhydride, which was then slowly added to the solid ethyl 2-(aminomethyl)-3-pyridinecarboxylate HCl and then stirred at rt for 8 h. Excess reagent was evaporated to give a residue, which was neutralized by very slow addition of sat. NaHCO3 solution. _Solution was extracted with DCM, dried and evaporated to provide ethyl imidazo[1,5-a]pyridine-8-carboxylate as a yellow solid (crude weight 2.7 g). MS: exact mass calculated for C10H10N2O2, 190.07; m/z found, 191 [M+H]+.
  • 2
  • [ 697739-12-1 ]
  • [ 697739-13-2 ]
YieldReaction ConditionsOperation in experiment
42% With potassium hydroxide; In methanol; for 0.5h;Heating / reflux; Description 36 (8.67 g, 45.6 mmol) and KOH [1. OM in methanol] (91.2 ml, 91.2 mmol) were mixed together and heated to reflux for 30 minutes when HPLC indicated the reaction was complete. The mixture was cooled and evaporated to dryness. Water (50 ml) was then added, and the mixture acidified with 2N HC1 to give a yellow precipitate. The precipitate was filtered and washed successively with water, ethanol, and diethyl ether to give the title compound (3.1 g, 42%) as a yellow solid
Ethyl imidazo [1, 5-a] pyridine-8-carboxylate (J. Het. CLIEIIZ., 1993,473) (0.21 g) was dissolved in 1M KOH in methanol (5 ml) and the solution heated at reflux for 5 min. The mixture was then concentrated, diluted with water (2 ml) and acidified to pH 1 with 2N HCI. The resulting precipitate was collected by filtration to give imidazo [1, 5-a] pyridine-8-carboxylic acid (80 mg) as a yellow solid.
  • 3
  • [ 64-18-6 ]
  • [ 697739-11-0 ]
  • [ 108-24-7 ]
  • [ 697739-12-1 ]
YieldReaction ConditionsOperation in experiment
56% Acetic anhydride (38. 21 ml, 405 mmol) and formic acid (15.28 ml, 405 mmol) were mixed together at 60 C for 2 hours then allowed to cool to room temperature. To this mixture was added Description 35 (17.55 g, 81 mmol), and the resulting mixture stirred at room temperature for 1 hour, then heated at 35 C for 3 hours. The mixture was cooled to 5 C and neutralised with 0.88 ammonia solution and then extracted with dichloromethane (3 x). The combined dichloromethane layers were washed with water, saturated NACI, dried over NA2S04, filtered and evaporated. The residue was purified by column chromatography on silica eluting with 2% MEOH in DCM + 0.5% NH40H to give the title compound (8.67 g, 56%).
  • 4
  • [ 614-18-6 ]
  • [ 697739-12-1 ]
  • 5
  • [ 14906-63-9 ]
  • [ 697739-12-1 ]
  • 6
  • [ 75358-90-6 ]
  • [ 697739-12-1 ]
  • 7
  • [ 697739-12-1 ]
  • [ 1446321-35-2 ]
  • 8
  • [ 697739-12-1 ]
  • imidazo<1,5-a>pyridine-8-methanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
[0144] To a cold solution of lithium aluminum hydride (1.62 g, 42,4 mmol, 4.0 eq) in THF (50 mL) was added the crude ethyl imidazo[l,5-a]pyridine-8-carboxylate (2.7 g, 14.2 mmol, 1.0 eq) and the reaction mixture was heated at reflux for 2 h. The reaction was cooled and water (1.7 mL), 15% NaOH (1.7 mL) and water (5.1 mL) were slowly added. Solution was diluted with excess EtOAc and stirred at rt for 30 min. The solution was filtered and the solid was washed with ethyl acetate. Organic layers were combined, dried and solvent was removed to give crude imidazo[l,5-a]pyridine-8-methanol, which was purified by column chromatography (EtOAc/ Hexane). MS: exact mass calculated for 148.06; m/z found, 149 [M+H] +.
With lithium aluminium tetrahydride; In tetrahydrofuran; for 2h;Reflux; [0251] To a cold solution of lithium aluminum hydride (1.62 g, 42,4 mmol, 4.0 eq) in THF (50 mL) was added the crude <strong>[697739-12-1]ethyl imidazo[1,5-a]pyridine-8-carboxylate</strong> (2.7 g, 14.2 mmol, 1.0 eq) and the reaction mixture was heated at reflux for 2 h. The reaction was cooled and water (1.7 mL), 15% NaOH (1.7 mL) and water (5.1 mL) were slowly added. Solution was diluted withexcess EtOAc and stirred at rt for 30 mm. The solution was filtered and the solid was washed with ethyl acetate. Organic layers were combined, dried and solvent was removed to give crude imidazo[1,5-a]pyridine-8-methanol, which was purified by column chromatography (EtOAc/ Hexane). MS: exact mass calculated for C8H8N20, 148.06; m/z found, 149 [M+H]+ .
With lithium aluminium tetrahydride; In tetrahydrofuran; for 2h;Reflux; Steps 5 and 6 :To a cold solution of lithium aluminum hydride (1.62 g, 42.4 mmol, 4.0 eq) in THF (50 mL) was added the crude <strong>[697739-12-1]ethyl imidazo[1,5-a]pyridine-8-carboxylate</strong> (2.7 g, 14.2 mmol, 1.0 eq) and the reaction mixture was heated at reflux for 2 h. The reaction was cooled and water (1.7 mL), 15% NaOH (1.7 mL) and water (5.1 mL) were slowly added. Solution was diluted with excess EtOAc and stirred at rt for 30 min. The solution was filtered and the solid was washed with ethyl acetate. Organic layers were combined, dried and solvent was removed to give crude imidazo[1,5-a]pyridine-8-methanol, which was purified by column chromatography (EtOAc/Hexane). MS: exact mass calculated for C8H8N2O, 148.06; m/z found, 149 [M+H]+.
With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 2h; To a solution of 550 <strong>[697739-12-1]ethyl imidazo[1,5-a]pyridine-8-carboxylate</strong> (2 g, 10.52 mmol) in 166 THF (20 mL) was added 192 LiAlH4 (798 mg, 21.0 mmol) with stirring at 0 C. The resulting suspension was stirred at 20 C. for 2 hours. The reaction mixture was cooled to 0 C. and was quenched with 55 water (2 mL), then diluted with ethyl acetate (200 mL). The resulting suspension was filtered through a pad of A1203 and concentrated. The residue was purified by column silica gel chromatography (Gradient: 0-10%, 113 MeOH in 68 dichloromethane) to give 551 imidazo[1,5-a]pyridin-8-ylmethanol.

  • 9
  • [ 697739-12-1 ]
  • [ 1446322-11-7 ]
  • 10
  • [ 697739-11-0 ]
  • [ 697739-12-1 ]
YieldReaction ConditionsOperation in experiment
With acetic anhydride; formyl acetic anhydride; at 20℃; for 8h; [0250] A mixture of 44.8 mL of acetic anhydride and 19.2 mL of formic acid was heated in a 50-60 C oil bath temperature for 3 h and then cooled to rt to give formic-acetic anhydride,which was then slowly added to the solid ethyl 2-(aminomethyl)-3-pyridinecarboxylate HCl andthen stirred at rt for 8 h. Excess reagent was evaporated to give a residue, which was neutralizedby very slow addition of sat. NaHCO3 solution. Solution was extracted with DCM, dried and evaporated to provide ethyl imidazo[1,5-a]pyridine-8-carboxylate as a yellow solid (crude weight 2.7 g). MS: exact mass calculated for C10H10N202, 190.07; m/z found, 191 [M+H]+ .
  • 11
  • [ 697739-12-1 ]
  • 8-(chloromethyl)imidazo[1,5-a]pyridine [ No CAS ]
  • 12
  • [ 697739-12-1 ]
  • 3-(imidazo[1,5-a]pyridin-8-ylmethoxy)isonicotinaldehyde [ No CAS ]
  • 13
  • [ 697739-12-1 ]
  • C15H13N3O3 [ No CAS ]
  • 14
  • [ 697739-12-1 ]
  • C14H11N3O3 [ No CAS ]
  • 15
  • [ 697739-12-1 ]
  • [ 151509-03-4 ]
 

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