Structure of 30766-22-4
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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. : | 30766-22-4 |
Formula : | C7H7NO3 |
M.W : | 153.14 |
SMILES Code : | OC1=CC(=CN=C1)C(=O)OC |
MDL No. : | MFCD00191521 |
InChI Key : | KJJSHOHQQHACLE-UHFFFAOYSA-N |
Pubchem ID : | 354317 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 37.54 |
TPSA ? Topological Polar Surface Area: Calculated from |
59.42 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.24 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.35 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.57 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.26 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.71 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.52 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.28 |
Solubility | 8.01 mg/ml ; 0.0523 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.16 |
Solubility | 10.5 mg/ml ; 0.0688 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.51 |
Solubility | 4.73 mg/ml ; 0.0309 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 |
No |
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 |
-6.99 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) |
1.5 |
* 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 |
---|---|---|
27% | With caesium carbonate; In N,N-dimethyl-formamide; at 20 - 40℃; for 71h; | [0400] A suspension of (S)-3-Methanesulfonyloxy-piperidine-l-carboxylic acid tert-bupsilonXyl ester (2 g, 7.15 mmol), 5-hydroxynicotinic acid methyl ester (2.19 g, 14.32 mmol), and CS2CO3 (4.89 g, 15.03 mmol) in DMF (14 ml) is stirred at room temperature for 1 hour. The reaction is then heated to 40° C for 70 hours. After cooling to room temperature and concentration in vacuo, the reaction is dissolved in water (100 ml), extracted with EtOAc (50 ml), dried over MgSO4, filtered, and concentrated in vacuo. The residue is then purified by silica gel chromatography (10-50percent EtOAc/Hexanes) to provide (R)-methyl 5-(l-( tert- butoxycarbonyl)piperidin-3-yloxy)nicotinate (643 mg, 27percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; toluene; at 0 - 20℃; for 24h;Inert atmosphere; | Triphenylphoshine (1052 mg, 4.01 mmol), 40% diethyl azodicarboxylatetoluene solution (698 mg, 4.01 mmol), and methyl 5-hydroxynicotinate(613 mg, 4.01 mmol) were added to a solution of 6(500 mg, 2.67 mmol) in tetrahydrofuran (18.0 mL) at 0 C under nitrogenatmospheric conditions. The resulting mixture was stirred for10 min and for an additional 24 h at room temperature and concentratedunder reduced pressure. The residue was purified by silica gelcolumn chromatography (petrolem ether/ethyl acetate=1/1) to yield7 (766 mg, 89%) in the form of a colorless oil: 1H NMR (300 MHz,CDCl3) δ: 8.83 (d, J=1.3 Hz, 1H), 8.51 (d, J=2.8 Hz, 1H), 7.81 (dd,J=2.8, 1.3 Hz 1H), 4.58-4.51 (m, 1H), 4.41-4.36 (m, 1H), 4.17 (dd,J=6.9, 2.9 Hz, 1H), 3.95 (s, 3H), 3.90 (t, J=7.5 Hz, 2H), 2.41-2.34(m, 1H), 2.31-2.26 (m, 1H), 1.42 (s, 9H); 13C NMR (75 MHz, CDCl3) δ:165.5, 155.9, 155.8, 142.9, 142.4, 126.3, 120.8, 79.5, 68.7, 59.8, 52.2, 46.9, 28.2 (3), 18.8; IR (CHCl3) cm-1: 3007, 2978, 2934, 1724, 1686,1589, 1394, 1367, 1302, 1151; FAB-MS m/z: 323.1611 (Calcd forC16H23N2O5: 323.1607); MS (FAB) m/z:323 (M++H, 62);[α]D20=-60.28 (c=1.01, CHCl3). |
88% | With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; toluene; at 0 - 20℃;Inert atmosphere; | Under N2 stream, to a solution of 1 (0.50 g, 2.7 mmol) in THF(18 mL), triphenylphosphine (0.61 g, 4.0 mmol), diethyl azodicarboxylate (40% solution in toluene, 1.87 mL), and methyl 5-hydroxynicotinate(0.61 g, 4.0 mmol) at 0 C were added. The mixture was stirred at 0 C for 10 min and then warmed up to room temperature and stirred overnight. After the reaction, solvent was removed under reduced pressure, followed by silica gel chromatography (petroleume ther/ethyl acetate=1/1) to yield 2 (0.77 g, 2.4 mmol, 88%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ; 8.83 (d, J=1.3 Hz, 1H),8.51 (d, J=2.8 Hz, 1H), 7.81 (dd, J=2.8, 1.3 Hz, 1H), 4.58-4.51 (m,1H), 4.41-4.36 (m, 1H), 4.17 (dd, J=6.9, 2.9 Hz, 1H), 3.95 (s, 3H),3.90 (t, J=7.5 Hz, 2H), 2.41-2.34 (m, 1H), 2.31-2.26 (m, 1H), 1.42 (s,9H). 13C NMR (75 MHz, CDCl3) δ; 165.5,155.9, 155.8, 142.9, 142.4,126.3, 120.8, 79.5, 68.7, 59.8, 52.2, 46.9, 28.2, 18.8. MS (FAB+) m/z;323 ([M+H]+). HRMS (FAB+) m/z; 323.1611 (Calcd: 323.1607 for C16H23N2O5+). [α]D20= -60.28 (c=1.01, CHCl3). |
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