Structure of 80194-83-8
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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. : | 80194-83-8 |
Formula : | C12H9ClN2O |
M.W : | 232.67 |
SMILES Code : | O=C(NC1=CC=CC=C1)C2=CC=NC(Cl)=C2 |
MDL No. : | MFCD09817650 |
Boiling Point : | No data available |
InChI Key : | LTAXNWGTCKPZGT-UHFFFAOYSA-N |
Pubchem ID : | 15075715 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 63.46 |
TPSA ? Topological Polar Surface Area: Calculated from |
41.99 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.98 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.47 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.8 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.01 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.69 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.59 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.83 |
Solubility | 0.0348 mg/ml ; 0.000149 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.03 |
Solubility | 0.0215 mg/ml ; 0.0000925 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.17 |
Solubility | 0.00159 mg/ml ; 0.00000684 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
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 |
-5.26 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 |
0.0 |
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 |
1.0 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) |
1.7 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 0 - 95℃; for 2 h; | To the sol. of 2-chloroisonicotinoyl chloride (Anderson, W. K. , Dean, D. C. , Endo, T., J Med Chem., 1990,33, 1667,10 g, 56.8 mmol) in 1,2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1,2-dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2Cl2 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233.1. |
92% | With N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 0 - 95℃; for 2 h; | 2-Chloro-N-phenylisonicotinamide (N); To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K. , Dean, D. C. , Endo, T., J. Med. Chem., 1990, 33, 1667,10 g, 56.8 mmol) in 1,2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1,2- dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2CI2 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233.1 |
92% | With N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 0 - 95℃; for 2 h; | 2-Chloro-N-phenylisonicotinamide (N) To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K. , Dean, D. C. , Endo, T., J. Med. Chem., 1990,33, 1667,10 g, 56. 8 mmol) in 1,2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1,2- dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2C12 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233.1. |
92% | With N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 0 - 95℃; for 2 h; | 2-Chloro-N-phenylisonicotinamide (N) To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K., Dean, D. C., Endo, T., J Med Chem., 1990, 33, 1667,10 g, 56. 8 mmol) in 1,2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1,2-dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2Cl2 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0. 87 min; ES+ = 233.1. |
92% | at 0 - 95℃; for 2 h; | 2-Chloro-N-phenylisonicotinamide (N); To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K., Dean, D. C. , Endo, T., J Med. Chem., 1990, 33, 1667,10 g, 56. 8 mmol) in 1,2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1,2- dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2C12 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233. 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With palladium diacetate; triethylamine; triphenylphosphine In N,N-dimethyl-formamide at 50℃; for 46 h; Autoclave | General procedure: In a typical experiment, Pd(OAc)2 (5.6 mg, 0.025 mmol), triphenylphosphine (13.1 mg, 0.05 mmol), 2,5-diiodopyridine(331 mg, 1 mmol), 2,3-diiodopyridine (331 mg, 1 mmol) or 2-chloro-3,4-diiodopyridine (182.75 mg, 0.5 mmol), amine nucleophile (see above in the tables; 3 mmol of a/2 mmol of b/1.5 mmol of c,d/1.1 mmol of e,f,g,h) and triethylamine (0.5 mL) were dissolved in DMF (10 mL) under argon in a 100 mL autoclave. The atmosphere was changed to carbon monoxide and the autoclave was pressurized to the given pressure by carbon monoxide. The reaction was conducted for the given reaction time upon stirring at 50 C andanalysed by GC-MS (internal standard: naphthalene). The mixture was then concentrated and evaporated to dryness and worked-up as described in Section 4.2. |
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