Structure of 113118-84-6
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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. : | 113118-84-6 |
Formula : | C12H9NO |
M.W : | 183.21 |
SMILES Code : | O=CC1=CN=CC(C2=CC=CC=C2)=C1 |
MDL No. : | MFCD03086178 |
InChI Key : | ACFVOZGSDCHVGJ-UHFFFAOYSA-N |
Pubchem ID : | 15519764 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 55.06 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.96 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.64 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.94 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.56 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.41 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.14 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.7 |
Solubility | 0.365 mg/ml ; 0.00199 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.19 |
Solubility | 1.17 mg/ml ; 0.0064 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.49 |
Solubility | 0.00593 mg/ml ; 0.0000324 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) |
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 |
-6.04 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 |
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) |
1.78 |
* 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 |
---|---|---|
EXAMPLE 11 5-Phenyl-3-pyridinecarboxaldehyde 5-Phenyl-3-(N-methoxy-N-methyl)pyridinecarboxamide (1.32 g, 5.45 mmol) was dissolved in THF (30 mL) under inert atmosphere, then cooled to -70 C. with stirring. Diisobutylaluminum hydride (11 mL of a 1M solution in cyclohexane, 11 mmol) was added. After addition was complete, the mixture was stirred at -70 C. for 2h. Saturated ammonium chloride solution (1 mL) was added to the reaction mixture, followed by water (15 mL) and chloroform (50 mL). The mixture was filtered through celite, the organic phase separated and the aqueous phase again extracted with chloroform (80 mL). The combined organic extracts were washed with water (2*50 mL), brine (50 mL), dried (MgSO4) and concentrated in vacuo. The crude material was chromatographed on silica gel with ethyl acetate-hexane (2:3) as eluant to afford the title compound as an oil, 790 mg, 80%. LRMS (EI) m/e 185 (M+ +2), 184 (M+ +H), 183 (M+), 182 (M+ -H); 1 H NMR (CDCl3, 300 MHz): delta10.20 (s, 1H), 9.08 (d, J=2 Hz, 1H), 9.05 (d, J=2 Hz, 1H), 8.35 (t, J=2 Hz, 1H), 7.63 (m, 2H), 7.45-7.55 (m, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium cyanoborohydride; In methanol; water; acetic acid; acetonitrile; | EXAMPLE 12 5-Phenyl-3-(N-pyrrolidinomethyl)pyridine <strong>[113118-84-6]5-Phenyl-3-pyridinecarboxaldehyde</strong> (400 mg, 2.18 mmol) and pyrrolidine (300 mg, 4.39 mmol) were dissolved in acetonitrile (20 mL) with stirring. The reaction mixture was chilled (0 C.), sodium cyanoborohydride (30 mg, 4.4 mmol) was added and the mixture stirred at 0 C. for 30 minutes. Glacial acetic acid (0.25 mL) was added dropwise and the mixture stirred at 25 C. for 18 h. 1M HCl (10 mL) and methanol (10 mL) were added and the mixture concentrated in vacuo. Water (20 mL) was added and the solution basified with solid sodium hydroxide. This was extracted with methylene chloride (3*30 mL) and the combined organic extracts were washed with water (20 mL), brine (20 mL), dried (MgSO4) and concentrated in vacuo. The crude material was chromatographed on silica gel with ethyl acetate-hexane (2:3) as eluant to afford the title compound as an oil, 360 mg, 70%. This was converted to the fumarate derivative of the title compound by the addition of one equivalent of fumaric acid to a methanol (10 mL) solution of the free amine at 25 C. After 30 minutes, the solvent was removed in vacuo and the residue pumped under high vacuum. Trituration with diethyl ether, followed by recrystallization from ethyl acetate afforded 5-phenyl-3-(N-pyrrolidinomethyl)pyridine fumarate; M.p. 126-127 C. (EtOAc); 1 H NMR (DMSO-d6, 300 MHz): delta8.82 (s, 1H), 8.62 (s, 1H), 8.20 (s, 1H), 7.72 (bs, 2H), 7.50 (bs, 3H), 6.58 (s, 2H), 4.15 (s, 2H), 2.97 (s, 4H), 1.85 (s, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 2.5h;Heating / reflux; | IA. S-Phenyl-pyridine-3-carbaldehyde: A biphasic mixture of 5- bromo-3-formyl pyridine (0.500 g, 2.69 mmol), Pd(Ph3P)4 (0.155 g, 0.134 mmol), and phenyl boronic acid (0.492 g, 4.03 mmol) in degassed 2.0 M aqueous Na2CO3 (6.0 mL) and toluene (6.7 mL) was heated at reflux for 2.5 h. The reaction was cooled to rt, diluted with water and EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc (Ix). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated to give an orange- brown oil weighing 0.848 g. Column chromatography on silica gel gave 0.447 g (91%) of the biaryl compound as a pale yellow solid. 1H NMR (500 MHz, CDCl3) delta: 10.19 (s, IH), 9.07 (s, IH), 9.04 (s, IH), 8.34 (s, IH), 7.62 (d, J = 7.7 Hz, 2H), 7.52 (t, J = 7.7 Hz, 2H), 7.47-7.44 (m, IH). MS 184.2 (M+H)+; 216.2 (M+CH3OH+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | General procedure: To a solution of compound 6(0.15 g, 0.45 mmol) and biphenyl-4-carbaldehyde a (0.1 g,0.55 mmol) in DMSO (2 mL) at 0 C was added Et3N (0.13mL, 0.97 mmol). After being stirred for 0.5 h at room temperature,NaBH(OAc)3 (0.11 g, 0.53 mmol) was added and the mixture was stirred for 6 h. The reaction was added sat.NaHCO3 solution (5 mL) and stirred for 15 min, followed by the addition of ethyl acetate (20 mL). The organic layer was separated and washed with sat. NaHCO3, brine, and dried over Na2SO4 and evaporated. Column chromatography on silica gel, eluting with methanol:dichloromethane (5:95) and then changing (10:90) afforded 0.099 g (55%) of compound 6a as an off-white solid, m.p. 134-135 C; IR (KBr) max.cm-1: 3431 (NH), 3062 (Ar-H), 2963 (Alph-H), 1703 (C=O),1620, 1512, 1430 (C=C), 1221 (C-N), 1168 (C-O). 1H NMR(500 MHz, DMSO-d6) = 2.71 (m, 4H, 2CH2); 3.14 (m, 4H,2CH2); 3.68 (s, 2H, CH2); 4.47 (s, 2H, CH2); 6.64 (d, 1H, J =2.3 Hz, aromatic H); 6.68 (d, 1H, J = 8.3 Hz, aromatic H);6.78 (dd, 1H, J = 2.2, 8.4 Hz, aromatic H); 7.43-7.48 (m, 5H,aromatic H); 7.58-7.61 (m, 4H, aromatic H); 13C NMR(125.7 MHz, DMSO-d6) = 43.78 (CH2), 50.11 (CH2), 53.02(CH2), 62.69 (CH2), 98.21 (aromatic-C), 114.64 (aromatic-C), 115.15 (aromatic-C), 117.28 (aromatic-C), 118.25 (aromatic-C), 127.18 (aromatic-C), 127.28 (aromatic-C), 127.53(aromatic-C), 127.91 (aromatic-C), 128.97 (aromatic-C),129.21 (aromatic-C), 130.29 (aromatic-C), 130.57 (aromatic-C), 140.92 (aromatic-C), 147.12 (aromatic-C), 156.34(C=O). Calculated (%) for C25H26N4O (398.21); C: 75.35, H:6.58, N: 14.06, found (%); C: 75.28, H: 6.64, N: 13.97. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | General procedure: To a solution of compound 6(0.15 g, 0.45 mmol) and biphenyl-4-carbaldehyde a (0.1 g,0.55 mmol) in DMSO (2 mL) at 0 C was added Et3N (0.13mL, 0.97 mmol). After being stirred for 0.5 h at room temperature,NaBH(OAc)3 (0.11 g, 0.53 mmol) was added and the mixture was stirred for 6 h. The reaction was added sat.NaHCO3 solution (5 mL) and stirred for 15 min, followed by the addition of ethyl acetate (20 mL). The organic layer was separated and washed with sat. NaHCO3, brine, and dried over Na2SO4 and evaporated. Column chromatography on silica gel, eluting with methanol:dichloromethane (5:95) and then changing (10:90) afforded 0.099 g (55%) of compound 6a as an off-white solid, m.p. 134-135 C; IR (KBr) max.cm-1: 3431 (NH), 3062 (Ar-H), 2963 (Alph-H), 1703 (C=O),1620, 1512, 1430 (C=C), 1221 (C-N), 1168 (C-O). 1H NMR(500 MHz, DMSO-d6) = 2.71 (m, 4H, 2CH2); 3.14 (m, 4H,2CH2); 3.68 (s, 2H, CH2); 4.47 (s, 2H, CH2); 6.64 (d, 1H, J =2.3 Hz, aromatic H); 6.68 (d, 1H, J = 8.3 Hz, aromatic H);6.78 (dd, 1H, J = 2.2, 8.4 Hz, aromatic H); 7.43-7.48 (m, 5H,aromatic H); 7.58-7.61 (m, 4H, aromatic H); 13C NMR(125.7 MHz, DMSO-d6) = 43.78 (CH2), 50.11 (CH2), 53.02(CH2), 62.69 (CH2), 98.21 (aromatic-C), 114.64 (aromatic-C), 115.15 (aromatic-C), 117.28 (aromatic-C), 118.25 (aromatic-C), 127.18 (aromatic-C), 127.28 (aromatic-C), 127.53(aromatic-C), 127.91 (aromatic-C), 128.97 (aromatic-C),129.21 (aromatic-C), 130.29 (aromatic-C), 130.57 (aromatic-C), 140.92 (aromatic-C), 147.12 (aromatic-C), 156.34(C=O). Calculated (%) for C25H26N4O (398.21); C: 75.35, H:6.58, N: 14.06, found (%); C: 75.28, H: 6.64, N: 13.97. |