Structure of 211678-96-5
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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. : | 211678-96-5 |
Formula : | C8H8ClNO2 |
M.W : | 185.61 |
SMILES Code : | O=C(OCC)C1=CC=NC=C1Cl |
MDL No. : | MFCD03411706 |
InChI Key : | VNSAFDGQUZWUFE-UHFFFAOYSA-N |
Pubchem ID : | 2762498 |
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 | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 45.33 |
TPSA ? Topological Polar Surface Area: Calculated from |
39.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.04 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.7 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.91 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.16 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.81 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.23 |
Solubility | 1.08 mg/ml ; 0.00584 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.14 |
Solubility | 1.35 mg/ml ; 0.00727 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.12 |
Solubility | 0.14 mg/ml ; 0.000753 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) |
Yes |
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 |
-6.23 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 |
0.55 |
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) |
1.65 |
* 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 |
---|---|---|
94% | 3-Chloro-isonicotinic acid ethyl esterCl O( so N. y[00263] A suspension of 3-chloro-isonicotinic acid (1.0 g, 6.35 mmol) in thionyl chloride (10 ml) was heated under reflux for 2.5 hours. After cooling to ambient temperature, the solution was concentrated to dryness and then azeotroped with toluene (10 ml) to afford an oil. The resultant oil was added dropwise over 10 minutes to a cooled (O0C) solution of ethanol (15 ml) and DIPEA (5 ml). The reaction was stirred at room temperature for 18 hours then concentrated in vacuo before water (20 ml) was added. The solution was extracted with ethyl acetate (30 ml) and the organic phase was dried over sodium sulfate then concentrated to give the title compound as an orange oil (1.1 g, 94%). IH NMR (CDCl3, 400MHz) 8.72 (s, IH), 8.59 (d, J = 4.9 Hz, IH), 7.63 (dd, J = 4.9 Hz, <n="70"/>0.5 Hz, IH), 4.44 (q, J = 7.3 Hz, 2H), 1.42 (t, J = 7.3 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With sodium hydride; In N,N-dimethyl-formamide; at 5 - 20℃; for 18.67h; | 3-Hvdroxv-thienor2,3-clpvridine-2-carboxylic acid ethyl ester[00265] To a cooled (50C) stirred solution of <strong>[211678-96-5]3-chloro-isonicotinic acid ethyl ester</strong>(1.11 g, 6.0 mmol) and mercapto-acetic acid ethyl ester (1.8 ml, 16.7 mmol) in anhydrous DMF (20 ml), under an argon atmosphere, was added sodium hydride (15.6 mmol, 60% dispersion in oil, 622 mg) in portions over 20 minutes. Stirring was continued at 50C for 20 minutes, followed by 18 hours at room temperature. The reaction mixture was then quenched by the addition of water (5 ml), acidified by the addition of acetic acid (1 ml), and subsequently concentrated to provide a residue. The residue was partitioned between ethyl acetate (150 ml) and water (50 ml). The organic phase was isolated, dried over sodium sulphate, filtered and evaporated to give a yellow oil. The oil was purified by flash chromatography (Si-SPE, pentane: ethyl acetate, gradient 80:20 to 30:70) to afford the title compound as a yellow solid (1.33 g, 99%). LCMS (method B): Rx = 2.57 min, M+H+ = 224. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid;Reflux; | A solution of 3-chloroisonicotinic acid (18.6 mmol) in 120 mL EtOH and 3 mL cone. H2S04 was heated to reflux overnight. The mixture was concentrated in vacuo, redissolved in aq. NaHC03 solution and extracted with EtOAc (2x). The combined organic layers were dried over MgS04 and concentrated in vacuo to give the desired product as yellow oil; LC-MS (A): tR = 0.63 min; [M+H]+: 186.08. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In tetrahydrofuran; at 20 - 70℃;Inert atmosphere; | Step-1 : Ethyl-3-ethylisonicotinate: To a mixture of <strong>[211678-96-5]ethyl 3-chloroisonicotinate</strong> (6.0 g, 32.3 mmol, prepared by following the procedure described in WO2008024724), and PdCl2(dppf)-CH2Cl2 adduct (1.05 g, 1.29 mmol) in dioxane (40 mL) at RTwas added drop-wisediethyl zinc (1M in THF, 32.3 mL, 32.3 mmol). The resulting mixture was thoroughly deoxygenated by subjecting to vacuum/nitrogen cycle three times and the reaction mixture was heated to 70 C and maintained for 4 h under nitrogen atmosphere. The reaction mixture was cooled to RT and then quenched with methanol (lmL). Water (lOmL)was added to the above mixture followed by ethyl acetate(50mL). The layers were separated and aqueous layer was extracted with ethyl acetate (3x75mL). The combined organic layers were washed with IN hydrochloric acid (50mL), water (50mL), brine (20mL) dried (Na2S04) and filtered. The filtrate was concentrated under vacuum. The crude product was purified by flash column chromatography to afford 2.30 g (40%) of the title compound as colorless oil HNMR (400 MHz, CDC13) delta 8.58 (s, 1H), 8.55 (d, = 5.0Hz, 1Eta), 7.64(d, = 5.0Hz, 1Eta), 4.42 (q, = 7.5Hz, 2Eta), 2.97 (q, = 7.0Hz, 2Eta), 1.41 (t, / = 7.5Hz, 3Eta) 1.26(t, / = 7.0Hz, 3H);GC-MS (m/z) 179 (M)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; In ethanol; | A.2.4.1 Synthesis of 3-chloroisonicotinic acid ethyl ester A solution of 3-chloroisonicotinic acid (18.6 mmol) in 120 mL EtOH and 3 mL conc. H2SO4 was heated to reflux overnight. The mixture was concentrated in vacuo, redissolved in aq. NaHCO3 solution and extracted with EtOAc (2*). The combined organic layers were dried over MgSO4 and concentrated in vacuo to give the desired product as yellow oil; LC-MS (A): tR=0.63 min; [M+H]+: 186.08. |
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