Structure of 80650-45-9
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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. : | 80650-45-9 |
Formula : | C11H10N2O |
M.W : | 186.21 |
SMILES Code : | N1=CC(=CC=C1)OC2=CC=C(C=C2)N |
MDL No. : | MFCD07186369 |
InChI Key : | ZSLIXJKSPVCNHZ-UHFFFAOYSA-N |
Pubchem ID : | 3159631 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H317 |
Precautionary Statements: | P280 |
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 | 1.0 |
Molar Refractivity | 55.16 |
TPSA ? Topological Polar Surface Area: Calculated from |
48.14 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.8 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.87 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.46 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.13 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.8 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.81 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.67 |
Solubility | 0.394 mg/ml ; 0.00211 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.5 |
Solubility | 0.585 mg/ml ; 0.00314 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.92 |
Solubility | 0.0222 mg/ml ; 0.000119 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) |
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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.11 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 |
1.0 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) |
2.04 |
* 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 |
---|---|---|
99% | With palladium 10% on activated carbon; hydrogen In methanol at 20℃; | Synthesis of compound 34-2 (0476) To the solution of 34-1 (2.0 g, 9.259 mmol) in MeOH (20 mL) was added 10percent Pd/C (0.2 g) purged with N2. Then H2 was added to remove N2. The mixture was stirred at room temperature overnight. After filtrated, the filtrate was concentrated to dryness affording 34-2 (1.7 g, 99percent) as brown solid. |
98% | With palladium 10% on activated carbon; hydrogen In methanol at 20℃; | Step 4. 4-(Pyridin-3-yloxy) aniline. 3-(4-nitrophenoxy)pyridine (10.2 g, 47.18 mmol) was dissolved in 100 mL MeOH, followed by addition of Pd/C powder (10percentwt, 1.1 g). The reaction mixture was stirred at r.t. under H2 atmosphere overnight and filtered through Celite. The filtrate was concentrated to afford 4-(pyridin-3-yloxy)aniline (17.45 g, 98percent yield) as grey solid. LC-MS: m/z: 187 (M+H)+. |
95% | With hydrogen In tetrahydrofuran; methanol at 20℃; | b) Compound 5 was hydrogenated at room temperature using PD/C in MEOH/THF. The reaction solution was filtered through kieselguhr and rinsed with MEOH, and the filtrate was subsequently evaporated. The residue was digested with diethyl ether, filtered off with suction, rinsed with diethyl ether and dried overnight at 40'C under reduced pressure. Yield : 37. 14 G (95percent) OF 6, PALE-BROWN CRYSTALS |
95% | With hydrogen In tetrahydrofuran; methanol at 20℃; | The thus obtained nitro comound was hydrogenated at room temperature using Pd/C in MeOH/THF. The reaction solution was filtered through kieselguhr and rinsed with MeOH, and the filtrate was subsequently evaporated. The residue was digested with diethyl ether, filtered off with suction, rinsed with diethyl, ether and dried overnight at 40°C under reduced pressure. Yield : 37.14 g (95percent) of 5b, pale-brown crystals |
95% | With hydrogen In tetrahydrofuran; methanol at 20℃; | Compound 5 is hydrogenated with Pd/C in [METHANOL/TETRAHYDROFURANE] at room temperature. The reaction mixture is filtered over kieselguhr, the residue washed with methanol and the filtrate evaporated. The residue is digested with diethyl ether, filtered by suction, washed with diethyl ether and dried in vacuum at 40 [°C] overnight to yield 37.14 g (95 percent) light brownish crystals of 6. |
95% | With hydrogen In tetrahydrofuran; methanol at 20℃; | b) Compound 5 is hydrogenated at room temperature using Pd/C in MeOH/THF. The reaction solution is filtered through kieselguhr and rinsed with MeOH, and the filtrate is subsequently evaporated. The residue is digested with diethyl ether, filtered off with suction, rinsed with diethyl ether and dried overnight at 40°C under reduced pressure. Yield : 37.14 g (95percent) of 6, pale-brown crystals |
95% | With hydrogen In ethyl acetate for 3.5 h; | A solution of 3- (4-nitrophenoxy)pyridine g, 23.13 mmol) in EtOAc (100 mL) in a 250 ml Parr bottle was purged with nitrogen. To this solution was added EtOAc-moistened 10percent Pd/C catalyst (500 mg, 10percent by weight). The reaction flask was placed in a Parr hygrogenation apparatus, purged with nitrogen (5x), evacuated, and then pressurized to 40 psi with hydrogen and shaken for 3.5 h. The reaction mixture was then purged with nitrogen, and filtered through a pad of Celite , rinsing with ethyl acetate (3x) and ethanol (3x). The filtrate was evaporated at reduced pressure to give a brown crystalline residue. The residue was stirred in diethyl ether at room temperature for 16 h and then filtered to provide 4.11 g (95percent) of the desired product as light brown crystals. (at)H-NMR (DMSO-d6) No. 8.21 (m, 2H), 7.30 (ddd, J = 8.4,4.6, 0.7 Hz, 1 H), 7.18 (ddd, J = 8.4, 2.9, 1.4 Hz, 1 H), 6.79 (d, J = 8.8 Hz, 2H), 6.58 (d, J = 9.0 Hz, 2H), 5.05 (br s, 2H) ; MS LC-MS [M+H]+ = 187, RT = 1.03 min. |
36% | With iron; ammonium chloride In tetrahydrofuran; methanol; water at 80℃; for 3 h; | 4-(Pyridin-3-yl)oxy-l -nitrobenzene prepared in Step A was dissolved in the mixture of water (100 mL), tetrahydrofuran (100 mL) and methanol (100 mL). Iron powder (103 g, 1.84 mol) and ammonium chloride (99 g, 1.84 mol) were added thereto, and the mixture was stirred for 3 h at 80 °C using a mechanical stirrer. After completion of the reaction, the reaction mixture was filtered through a cellite, washed with methanol, and concentrated under reduced pressure. The solid thus obtained was filtered, washed with ether, and dried to give the title compound (17 g, Yield 36percent). Mass[M+H] : 186 (M+l) |
36% | With iron; ammonium chloride In tetrahydrofuran; methanol at 80℃; for 3 h; | The compound thus obtained was dissolved using water (100ml), tetrahydrofuran (100ml) and methanol (100ml). Iron powder (103g, 1.84 mol) and ammonium chloride (99g, 1.84 mol) were added thereto, and the mixture was stirred using a mechanical stirrer for 3 h at 80 "C . After completion of the reaction, the reaction solution was filtered through a celite, washed with methanol, and concentrated.The resulting solid was filtered, washed with ether, and dried to give 4-(pyridin-3- yloxy)-phenylamine ( 17g, Yield 36percent). |
36% | With water; iron; ammonium chloride In tetrahydrofuran; methanol at 80℃; for 3 h; | 4-(Pyridin-3-yl)oxy-1-nitrobenzene prepared in Step A was dissolved in the mixture of water (100 mL), tetrahydrofuran (100 mL) and methanol (100 mL). Iron powder (103 g, 1.84 mol) and ammonium chloride (99 g, 1.84 mol) were added thereto, and the mixture was stirred for 3 h at 80° C. using a mechanical stirrer. After completion of the reaction, the reaction mixture was filtered through a cellite, washed with methanol, and concentrated under reduced pressure. The solid thus obtained was filtered, washed with ether, and dried to give the title compound (17 g, Yield 36percent). |