Structure of 53241-90-0
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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. : | 53241-90-0 |
Formula : | C14H18N2O5 |
M.W : | 294.30 |
SMILES Code : | O=C(OCC)C(C(OCC)=O)=CNC1=CC=C(OC)N=C1 |
MDL No. : | MFCD08457989 |
InChI Key : | FJDMNLFVZHBIHR-UHFFFAOYSA-N |
Pubchem ID : | 619151 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 21 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.36 |
Num. rotatable bonds | 9 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 75.78 |
TPSA ? Topological Polar Surface Area: Calculated from |
86.75 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.25 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.48 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.32 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.41 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.5 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.79 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.84 |
Solubility | 0.421 mg/ml ; 0.00143 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.95 |
Solubility | 0.0333 mg/ml ; 0.000113 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.25 |
Solubility | 0.166 mg/ml ; 0.000564 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) |
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 |
-6.33 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 |
4.0 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) |
2.91 |
* 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 |
---|---|---|
73% | With diphenyl ether-biphenyl eutectic; for 0.333333h;Heating / reflux; | Dowtherm A (Fluka, 500 mL) was brought to boiling (250 0C) in a 2 L 3-neck flask fitted with a still-head and a reflux condenser. 2-[(6-Methoxypyridin-3- ylamino)methylene]malonic acid diethyl ester (100 g, 0.34 mole) was added portion-wise over 5 min. The solution was heated at reflux for an additional 15 min, allowing some solvent to distil over. The resulting solution was cooled to room temperature and diluted with hexane (750 mL). The mixture was cooled in ice for 1 h, then the brown solid was filtered off, washed with hexane, and dried under vacuum to afford the title compound (61.72g, 73%). |
73% | In diphenyl ether-biphenyl eutectic; at 250℃; for 0.333333h;Heating / reflux; | b) 6-Methoxy-4-oxo-1 ,4-dihvdro-ϖ ,51naphthyridine-3-carboxylic acid ethyl ester; b) _Dowthemn A (Fluka, 500 ml_) was brought to boiling (250 0C) in a 2 L 3-neck flask fitted with a still-head and a reflux condenser. 2-[(6-Methoxypyridin-3- ylamino)methylene]malonic acid diethyl ester (100 g, 0.34 mole) was added portionwise over 5 min. The solution was heated at reflux for an additional 15 min, allowing some solvent to distill over. The resulting solution was cooled to RT and diluted with hexanes (750 ml_). The mixture was cooled in ice for 1 hr, then the brown solid was filtered off, washed with hexanes, and dried under vacuum to afford the title compound (61.72g, 73%). |
73% | In diphenyl ether-biphenyl eutectic; at 250℃; for 0.333333h;Heating / reflux; | (b) 6-Methoxy-4-oxo-1 ,4-dihydro-[1 ,5]naphthyridine-3-carboxylic acid ethyl ester; Dowtherm A (Fluka, 500 ml_) was brought to boiling (250 C) in a 2 L 3-neck flask fitted with a still-head and a reflux condenser. 2-[(6-Methoxypyridin-3- ylamino)methylene]malonic acid diethyl ester (100 g, 0.34 mole) was added portion-wise over 5 min. The solution was heated at reflux for an additional 15 min, allowing some solvent to distil over. The resulting solution was cooled to room temperature and diluted with hexane (750 ml_). The mixture was cooled in ice for 1 h, then the brown solid was filtered off, washed with hexane, and dried under vacuum to afford the title compound (61.72g, 73%). |
73% | With diphenyl ether-biphenyl eutectic; for 0.333333h;Heating / reflux; | _Dowtherm A (Fluka, 500 ml_) was brought to boiling (250 0C) in a 2 L 3-neck flask fitted with a still-head and a reflux condenser. 2-[(6-Methoxypyridin-3- ylamino)methylene]malonic acid diethyl ester (100 g, 0.34 mole) was added portionwise over 5 min. The solution was heated at reflux for an additional 15 min, allowing some solvent to distill over. The resulting solution was cooled to RT and diluted with hexanes (750 ml_). The mixture was cooled in ice for 1 hr, then the brown solid was filtered off, washed with hexanes, and dried under vacuum to afford the title compound (61.72g, 73%). |
73% | In diphenyl ether-biphenyl eutectic; at 250℃; for 0.333333h; | b) 6-Methoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic acid ethyl ester; Dowtherm A (Fluka, 500 mL) was brought to boiling (250 C.) in a 2 L 3-neck flask fitted with a still-head and a reflux condenser. 2-[(6-Methoxypyridin-3-ylamino)methylene]malonic acid diethyl ester (100 g, 0.34 mole) was added portionwise over 5 min. The solution was heated at reflux for an additional 15 min, allowing some solvent to distil over. The resulting solution was cooled to RT and diluted with hexanes (750 mL). The mixture was cooled in ice for 1 hr, then the brown solid was filtered off, washed with hexanes, and dried under vacuum to afford the title compound (61.72 g, 73%). |
73% | In diphenyl ether-biphenyl eutectic; at 250℃; for 0.333333h; | b) 6-Methoxy-4-oxo-1 ,4-dihvdro-ri ,51naphthyridine-3-carboxylic acid ethyl ester; Dowtherm A (Fluka, 500 mL) was brought to boiling (250 0C) in a 2 L 3-neck flask fitted with a still-head and a reflux condenser. 2-[(6-Methoxypyridin-3- ylamino)methylene]malonic acid diethyl ester (100 g, 0.34 mole) was added portionwise over 5 min. The solution was heated at reflux for an additional 15 min, allowing some solvent to distil over. The resulting solution was cooled to RT and diluted with hexanes (750 mL). The mixture was cooled in ice for 1 hr, then the brown solid was filtered off, washed with hexanes, and dried under vacuum to afford the title compound (61.72g, 73%). |
73% | In diphenyl ether-biphenyl eutectic; at 250℃; for 0.333333h;Heating / reflux; | (b) 6-Methoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic acid ethyl ester; Dowtherm A (Fluka, 500 mL) was brought to boiling (250 C) in a 2 L 3-neck flaskfitted with a still-head and a reflux condenser. 2-[(6-Methoxypyridin-3-ylamino)methylene]malonic acid diethyl ester (100 g, 0.34 mole) was added portion-wiseover 5 min. The solution was heated at reflux for an additional 15 min, allowing somesolvent to distil over. The resulting solution was cooled to room temperature and dilutedwith hexane (750 mL). The mixture was cooled in ice for 1 h, then the brown solid wasun, wctsiitju wiin HCACUIC, and dried under vacuum to afford the title compound(61.72g, 73%).; b) 6-Methoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic acid ethyl ester; Dowtherm A (Fluka, 500 ml) was brought to boiling (250 C) in a 2 L 3-neck flaskfitted with a still-head and a reflux condenser. 2-[(6-Methoxypyridin-3-ylamino)methylene]malonib acid diethyl ester (100 g, 0.34 mole) was added portion-wiseover 5 min. The solution was heated at reflux for an additional 15 min, allowing somesolvent to distil over. The resulting solution was cooled to RT and diluted with hexanes(750 ml_). The mixture was cooled in ice for 1 hr, then the brown solid was filtered off,washed with hexanes, and dried under vacuum to afford the title compound (61.72g,73%). |
73% | With dowtherm A; for 0.25h;Heating / reflux; | b) 6-Methoxy-4-oxo-1 ,4-dihydro-[1 ,5]naphthyridine-3-carboxylic acid ethyl ester Dowtherm A (Fluka, 500 mL) was brought to boiling (250 0C) in a 2 L 3-neck flask fitted with a still-head and a reflux condenser. 2-[(6-Methoxypyridin-3- ylamino)methylene]malonic acid diethyl ester (100 g, 0.34 mole) was added portionwise over 5 min. The solution was heated at reflux for an additional 15 min, allowing some solvent to distil over. The resulting solution was cooled to RT and diluted with hexanes (750 mL). The mixture was cooled in ice for 1 hr, then the brown solid was filtered off, washed with hexanes, and dried under vacuum to afford the title compound (61.72g, 73%). |
73% | In diphenyl ether-biphenyl eutectic; at 250℃; for 0.333333h;Heating / reflux;Product distribution / selectivity; | Dowtherm A (Fluka, 500 mL) was brought to boiling (250 0C) in a 2 L 3-neck flask fitted with a still-head and a reflux condenser. 2-[(6-Methoxypyridin-3- ylamino)methylene]malonic acid diethyl ester (100 g, 0.34 mole) was added portion-wise over 5 min. The solution was heated at reflux for an additional 15 min, allowing some solvent to distil over. The resulting solution was cooled to RT and diluted with hexanes (750 mL). The mixture was cooled in ice for 1 hr, then the brown solid was filtered off, washed with hexanes, and dried under vacuum to afford the title compound (61.72g,73%) b. 6-methoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic acid ethyl ester Dowtherm A (Fluka, 500 mL) was brought to boiling (250 0C) in a 2 L 3-neck flask fitted with a still-head and a reflux condenser. 2-[(6-Methoxypyridin-3- ylamino)methylene]malonic acid diethyl ester (100 g, 0.34 mole) was added portionwise over 5 min. The solution was heated at reflux for an additional 15 min, allowing some solvent to distill over. The resulting solution was cooled to RT and diluted with hexanes (750 ml_). The mixture was cooled in ice for 1 hr, and the resulting brown precipitate was filtered off, washed with hexanes, and dried under vacuum to afford the title compound (61.72g, 73%). |
73% | In diphenyl ether-biphenyl eutectic; for 0.333333h;Heating / reflux; | Dowtherm A (Fluka, 500 mL) was brought to boiling (250 0C) in a 2 L 3-neck flask fitted with a still-head and a reflux condenser. 2-[(6-Methoxypyridin-3- ylamino)methylene]malonic acid diethyl ester (100 g, 0.34 mole) was added portionwise over 5 min. The solution was heated at reflux for an additional 15 min, allowing some solvent to distil over. The resulting solution was cooled to room temperature and diluted with hexane (750 mL). The mixture was cooled in ice for 1 h, then the brown solid was EPO <DP n="22"/>filtered off, washed with hexane, and dried under vacuum to afford the title compound (61.7g, 73%) as a grey solid which was used without further purification: LC/MS (ES) m/z249 [M+H]+ |
32% | In diphenylether; at 245℃;Inert atmosphere; | Preparation of 6-methoxy-4-oxo-l,4-dihvdro-ri,51naphthyridine-3-carboxylic acid ethyl ester: A solution of 2-[(6-methoxy-pyridin-3-ylamino)-methylene]-malonic acid diethyl ester (260.0 g, 1.365 mol, 1.0 eq) in diphenyl ether (500 mL) is heated to reflux. While the ethanol formed is removed by azeotropic distillation the reflux temperature reached 245 0C. The reaction mixture is kept at 2450C for 3 hours, then it is cooled to 28 0C, a brown solid precipitated and is collected by filtration and washed with hexane (500 mL). The solid is dried under vacuum to afford 6-methoxy-4-oxo-l,4-dihydro-[l,5]naphthyridine-3- carboxylic acid ethyl ester as a brown powder (74.2 g, 32% yield).1H-NMR (400 MHz, DMSO-t/6) δ ppm: 12.28 (s, IH), 8.47 (s, IH), 7.98 (d, J = 9.2 Hz,IH), 7.18 (d, IH, J = 9.2 Hz), 4.20 (d, J = 7.2 Hz, 2H). 3.93 (s, 3H), 1.27 (t, J = 7.2 Hz,3H).MS m/z (+ESI): 249.1 [M+H]+. |
1.04 g | With Dowtherm A; at -20 - 250℃; | Dowtherm A (10 mL) was brought to boiling (250) in a 50 mL 3-necked flask fitted with a still-head and a reflux condenser. Diethyl [(6- methoxypyridin-3-yl)amino]methylidene}propanedioate (2.1 g, 7.2 mmol) was added portion-wise. The mixture was boiled for 15' then it was cooled to room temperature, diluted with Cy (15 mL) and cooled at -20C overnight. The brown precipitate was filtered and washed with Cy to obtain a brown solid that was triturated with EtOAc. The suspension was filtered to give ethyl 6-methoxy-4-oxo-1 ,4-dihydro-1 ,5-naphthyridine-3-carboxylate as a grey solid (1 .04 g, 4.2 mmol, 58% yield). LC-MS (M-H+) = 249.2 |
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