Structure of 103878-09-7
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
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 |
59.42 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.26 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.05 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.18 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.03 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.04 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.7 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.71 |
Solubility | 3.26 mg/ml ; 0.0195 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.89 |
Solubility | 2.16 mg/ml ; 0.0129 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.92 |
Solubility | 1.99 mg/ml ; 0.0119 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.57 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.78 |
* 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.
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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 |
Yield | Reaction Conditions | Operation 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 |
Yield | Reaction Conditions | Operation 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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