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Structure of 103878-09-7

Chemical Structure| 103878-09-7

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Product Details of [ 103878-09-7 ]

CAS No. :103878-09-7
Formula : C8H9NO3
M.W : 167.16
SMILES Code : O=C(O)C1=NC=CC=C1OCC
MDL No. :MFCD11878609
InChI Key :QTVCNUYGSSNMDT-UHFFFAOYSA-N
Pubchem ID :21333204

Safety of [ 103878-09-7 ]

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

Computational Chemistry of [ 103878-09-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 42.5
TPSA ?

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

59.42 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

1.05
Log Po/w (WLOGP)?

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

1.18
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.

-1.03
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

1.04
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.7

Water Solubility

Log S (ESOL):?

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

-1.71
Solubility 3.26 mg/ml ; 0.0195 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.

-1.89
Solubility 2.16 mg/ml ; 0.0129 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

-1.92
Solubility 1.99 mg/ml ; 0.0119 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.

-6.57 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)

1.78

Application In Synthesis of [ 103878-09-7 ]

* 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 [ 103878-09-7 ]

[ 103878-09-7 ] Synthesis Path-Downstream   1~6

  • 2
  • [ 57260-73-8 ]
  • [ 103878-09-7 ]
  • [ 530-62-1 ]
  • [ 103878-10-0 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; dichloromethane; water; EXAMPLE 7 4.0 g of <strong>[103878-09-7]3-ethoxy-2-pyridinecarboxylic acid</strong> and 4.1 g of 1,1'-carbonyldiimidazole were stirred at 70 for 2 hours in 250 ml of tetrahydrofuran. To this solution were then added dropwise 4.1 g of N-(t-butoxycarbonyl)ethylenediamine in 20 ml of tetrahydrofuran and the mixture was left to stir at 70 for a further 2 hours. The reaction mixture was subsequently cooled to room temperature and concentrated to about 1/4 of the volume on a rotary evaporator under reduced pressure, taken up in water and extracted three times with chloroform. The chloroform extracts, dried over magnesium sulfate, were evaporated completely, and the residue was chromatographed on silica gel with 2-5% methanol in methylene chloride as the elution agent and crystallized from methylene chloride/n-hexane, whereby there was obtained t-butyl [2-(3-ethoxypyridine-2-carboxamido)ethyl]carbamate, m.p. 125-126.
  • 3
  • (1S,2S)-1-N-[5-(trifluoromethyl)pyrazin-2-yl]cyclopentane-1,2-diamine hydrochloride [ No CAS ]
  • [ 103878-09-7 ]
  • 3-ethoxy-N-[(1S,2S)-2-[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; Example 60 3-Ethoxy-N-[(1S,2S)-2-[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]pyridine-2-carboxamide A solution of (1S,2S)-1-N-[5-(trifluoromethyl)pyrazin-2-yl]cyclopentane-1,2-diamine hydrochloride (Intermediate 14; 150 mg, 0.53 mmol), <strong>[103878-09-7]3-ethoxypyridine-2-carboxylic acid</strong> (CAS number 103878-09-7; 106 mg, 0.64 mmol), EDC (153 mg, 0.80 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (108 mg, 0.80 mmol) and triethylamine (0.222 ml, 1.59 mmol) in DCM (1 ml) was stirred at room temperature over the weekend. The mixture was partitioned between ethyl acetate (50 ml) and water (20 ml). The organics were washed with water (2*20 ml) and brine (20 ml), dried over sodium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography (basic silica, 30-100% ethyl acetate/petrol) and then by reverse phase chromatography (C18 silica, 0-100% water (with 0.05% ammonia)/acetonitrile) to afford the title compound. 1H NMR (400 MHz, DMSO-d6) delta ppm 1.08-1.29 (m, 3H), 1.41-1.63 (m, 2H), 1.66-1.80 (m, 2H), 2.01-2.16 (m, 2H), 3.94-4.09 (m, 2H), 4.16-4.34 (m, 2H), 7.35-7.44 (m, 1H), 7.46-7.55 (m, 1H), 7.96-8.16 (m, 3H), 8.26-8.46 (m, 2H) MS ES+: 396
  • 4
  • [ 62733-99-7 ]
  • [ 103878-09-7 ]
  • 5
  • [ 57767-50-7 ]
  • [ 103878-09-7 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In tetrahydrofuran; at 20 - 25℃; for 17.0h; A solution of methyl 3-ethoxypyridine-2-carboxylate (1.18 g, 6.53 mmol) and NaOH (2 M, 16.3 ml, 32.6 mmol) in THF (22 ml) was stirred at room temperature for 17 hours. The reaction mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and water. The aqueous layer was acidified to pH 5 and extracted with ethyl acetate, the product remained in the aqueous which was concentrated in vacuo to afford the title compound, (0432) 1H NMR (300 MHz, DMSO- ,) delta ppm 1 ,21 - 1 ,34 (m, 3 H), 3,91 - 4.06 (m, 2 H), 6.98 - 7, 1 1 (m, 1 H), 7.16 - 7,28 (m, 1 H), 7,82 - 7,94 (m, 1 H) (0433) MS ES+: 168
  • 6
  • (1S,2S)-1-N-(6-fluoro-1,3-benzothiazol-2-yl)cyclopentane-1,2-diamine hydrochloride [ No CAS ]
  • [ 103878-09-7 ]
  • 3-ethoxy-N-[(1S,2S)-2-[(6-fluoro-1,3-benzothiazol-2-yl)amino]cyclopentyl]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; HATU; In dichloromethane; at 20 - 25℃; for 17.0h; To a slurry of (iS,25T)-l-iV-(6-fluoi -l,3-benzothiazoi-2-yl)cyclopentane-l,2-diamine hydrochloride (Intermediate 1; 100 mg, 0.35 mmol) in dry DCM (1.2 ml) was added 3- ethoxypyridine-2-carboxylic acid hydrochloride (Intermediate 5, 78 mg, 0,38 mmol), HATU (198 mg, 0.52 mmol) and triethyiamine (145 mu, 1.04 mmol). The reaction mixture was stirred at room temperature for 17 hours then partitioned between DCM and a saturated solution of sodium bicarbonate. The organics were filtered through a (0581) hydrophobic frit and concentrated in vacuo. The crude material was purified by reverse phase preparative HPLC (eluted with acetonitriie / water containing 0.1 % ammonia) to afford the title compound. (0582) 1H MR (400 MHz, DCM-cfc) delta ppm 1.43 - 1.55 (m, 3 H), 1.64 - 1.77 (m, 2 H), 1.86 - 1.98 (m, 2 H), 2.23 - 2.36 (m, 1 H), 2.45 - 2.60 (m, 1 H), 3.96 - 4.09 (m. 1 H), 4.10 - 4.23 (m, 2 H), 4.31 - 4.48 (m, 1 H), 6.94 - 7.07 (m, 1 H), 7.24 - 7.33 (m, 1 H), 7.35 - 7,46 (m, 3 H), 8.06 - 8.24 (m, 2 H) (0583) MS ES+: 401
 

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