Structure of 13472-83-8
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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. : | 13472-83-8 |
Formula : | C6H7NO2 |
M.W : | 125.13 |
SMILES Code : | OC1=CC=CN=C1OC |
MDL No. : | MFCD00457990 |
InChI Key : | RDBZAWZPZSBYDA-UHFFFAOYSA-N |
Pubchem ID : | 747009 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 32.75 |
TPSA ? Topological Polar Surface Area: Calculated from |
42.35 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.59 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.8 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.8 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.07 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.88 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.8 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.55 |
Solubility | 3.55 mg/ml ; 0.0284 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.27 |
Solubility | 6.71 mg/ml ; 0.0536 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.53 |
Solubility | 3.66 mg/ml ; 0.0292 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) |
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 |
-6.5 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) |
1.59 |
* 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 |
---|---|---|
With potassium carbonate; In acetonitrile; | The starting material can be obtained as follows: A mixture of 15.4 g of <strong>[13472-83-8]3-hydroxy-2-methoxy-pyridine</strong>, 16 g of potassium carbonate, 25 ml of epichlorohydrin and 150 ml of acetonitrile is refluxed for 7 hours. Cooling and filtering the mixture and evaporating the filtrate yields crude 3-(2,3-epoxy-propoxy)-2-methoxypyridine, which is used without further purification. In an analogous manner, 1-{1-[2-hydroxy-3-(2-methoxy-6-methyl-3-pyridyloxy)-propyl]-4-piperidyl}-imidazolidin-2-one, which after recrystallisation from a mixture of methylene chloride and diethyl ether melts at 144-147, can be obtained by reacting 20 g of crude 3-(2,3-epoxy-propoxy)-2-methoxy-6-methyl-pyridine and 16.5 g of 1-(4-piperidyl)-imidazolidin-2-one. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With triethylamine;copper diacetate; In dichloromethane; at 20℃; for 48.0h;Molecular sieve; | (1) Production of 2-methoxy-3-[4-(trifluoromethyl)phenoxy]pyridine: [4-(Trifluoromethyl)phenyl]boronic acid (668 mg, 3.52 mmol), copper(II) acetate (480 mg, 2.64 mmol), triethylamine (0.74 mL, 5.28 mmol) and Molecular Sieve 4A (1.76 g) were added to a methylene chloride solution (20 mL) of <strong>[13472-83-8]2-methoxypyridin-3-ol</strong> (220 mg, 1.76 mmol), and stirred at room temperature for 2 days. The reaction liquid was filtered through Celite, then aqueous saturated sodium hydrogencarbonate solution was added to the filtrate, and extracted with ethyl acetate. The obtained organic layer was washed with saturated saline, then dried with anhydrous sodium sulfate, and filtered. The obtained filtrate was concentrated under reduced pressure, then the residue was purified by silica gel column chromatography (hexane:ethyl acetate = 10:0 to 9:1) to obtain the entitled compound (298 mg, 63 %). Mass Spectrum (ESI): 270.0 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In DMF (N,N-dimethyl-formamide); for 6.0h;Heating / reflux; | To a mixture of 10 g of 3-(2,5-difluoro-4-nitrophenyl)-1-methyl-6-triffuoromethyl-1H-pyrimidin-2,4-dione, 5.0 g of <strong>[13472-83-8]3-hydroxy-2-methoxypyridine</strong> and 100 ml of N,N-dimethylformamide, 7.8 g of potassium carbonate were added and refluxed for 6 hours under stirring. Then, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with aqueous sodium bicarbonate and saturated brine subsequently, dried over magnesium sulfate and concentrated to give 12.8 g of 3-[4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-2-nitro-1,2,3,6-tetrahydropyrimidin-1-yl)phenoxy]-2-methoxypyridine.1H-NMR (300M Hz, CDCl3, TMS delta (ppm)): 3.52 (3H, q, J=1.2 Hz), 3.93 (3H, s), 6.32 (1H, s), 6.76 (1H, d, J=5.8 Hz), 6.93 (1H, dd, J=5.0 Hz, 7.8 Hz), 7.40 (1H, dd, J=1.4 Hz, 7.8 Hz), 7.90 (1H, d, J=8.6 Hz), 8.04 (1H, dd, J=1.4 Hz, 5.0 Hz) | |
With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 2.0h; | Step A: Preparation of 3-[2-fluoro-5-[(2-methoxy-3-pyridinyl)oxy]-4-nitrophenyl]-l- methyl-6-(trifluoromethyl)-2,4(lH,3H)-pyrimidinedioneA mixture of 3-(2,5-difiuoro-4-nitrophenyl)-l-methyl-6-(trifluoromethyl)-2,4(lH,3H)- pyrimidinedione (2.25 g, 6.4 mmol) (prepared as described in WO 02/098227), 2-methoxy- 3-pyridinol (800 mg, 6.4 mmol) and potassium carbonate (1.06 g, 7.68 mmol) in N,N- dimethylformamide (15 mL) was heated to 70 C for 2 h, then allowed to cool. The resulting reaction mixture was filtered and the potassium carbonate was washed with ethyl acetate. The combined filtrates were concentrated in vacuo and the resulting residue was subjected to silica gel column chromatography eluting with ethyl acetate in hexanes to give the title compound as a light brown solid (2.82 g).in NMR delta 7.90 (d, 1H), 7.40 (m, 1H), 6.93 (m, 2H), 6.76 (m, 1H), 6.32 (s, 1H), 3.92 (s, 3H), 3.53 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; | General procedure: To a solution of 4-(chloromethyl)-i -(3-(difluoromethyl)phenyl)-i H-i 2,3-triazole (25 mg, 0.103 mmol) and 2-amino-5-chloropyrimidine (17 mg, 0.13mmol) in DMF (1.5 mL) was added K2003 (57 mg, 0.41 mmol). The resultingmixture was stirred at 100 C for 72 h. The reaction mixture was diluted withwater (8 mL) and extracted with EtOAc (3 x 10 mL). The combined organicswere dried over Na2504, filtered, and concentrated under reduced pressure.Purification (FCC, 5i02, 0-80% EtOAc/hexanes) afforded the title compound(6.2 mg, 18%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With caesium carbonate; In dimethyl sulfoxide; at 140℃; for 1.0h;Microwave irradiation; | A mixture of 4-nitrophenyl (S)-4-((4-chlorobenzamido)(phenyl)methyl)piperidine-1 - carboxylate (100 mg, 0.20 mmol), <strong>[13472-83-8]2-methoxypyridin-3-ol</strong> (100 mg, 0.80 mmol), Cs2C03(130 mg, 0.40 mmol) and DMSO (2.5 mL) was heated to 140C by microwave. After stirred at this temperature for 1 h, the reaction mixture was partitioned between EtOAc/H20, and the layers were separated. The organic layer was washed with brine and dried over Na2S04. Solvent was removed under vacuum and the residue was purified by Gilson (C18, 10-50% MeCN in water with 0.1 % formic acid) to afford the title compound (78 mg, 81 %) as a white solid.1H NMR (400 MHz, DMSO) delta 8.90 (d, J = 8.6 Hz, 1 H), 8.01 (d, J = 3.6 Hz, 1 H), 7.89 (d, J = 8.5 Hz, 2H), 7.61 - 7.48 (m, 3H), 7.47 - 7.40 (m, 2H), 7.34 (t, J = 7.5 Hz, 2H), 7.28 - 7.22 (m, 1 H), 7.03 - 6.97 (m, 1 H), 4.81 (t, J = 9.2 Hz, 1 H), 4.20 - 3.93 (m, 2H), 3.85 (s, 3H), 3.00 - 2.78 (m, 2H), 2.13 - 1 .95 (m, 2H), 1 .34 - 1 .13 (m, 3H). LCMS (ESI) m/z calcd for C26H26CIN3O4: 479.16. Found: 480.28/482.23 (M/M+2)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With caesium carbonate; In N,N-dimethyl-formamide; at 75℃; for 0.166667h; | A mixture of 4,5-dichloro-2-fluoro-benzaldehyde (502 mg, 2.60 mmol), 2-methoxypyridin-3- ol (325 mg, 2.60 mmol) and cesium carbonate (1.02 g, 3.12 mmol) in DMF (4 mL) was heated at 75 C for 10 minutes. The cooled reaction mixture was diluted with ethyl acetate (50 mL) then partitioned with water (50 mL). The aqueous portion was extracted with ethyl acetate (2 x 25 mL) and the combined organics were washed with saturated sodium chloride solution (2 x 25 mL), dried over sodium sulfate concentrated in vacuo. The product was purified by silica gel chromatography (0-100% ethyl acetate/hexanes) to provide 4,5-dichloro-2-[(2-methoxy-3-pyridyl)oxy]benzaldehyde (650 mg, 84%). ESI-MS m/z calc. 297.00, found 298.1 (M+l)+; Retention time (Method A): 0.68 minutes (1 minutes run). 1H NMR (400 MHz, DMSO-d6) 5 10.35 (s, 1H), 8.12 (dd, J = 5.0, 1.6 Hz, 1H), 7.97 (s, 1H), 7.70 (dd, J = 7.7, 1.6 Hz, 1H), 7.14 - 7.08 (m, 2H), 3.87 (s, 3H) ppm |