Structure of 1375301-90-8
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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. : | 1375301-90-8 |
Formula : | C8H5BrN2O |
M.W : | 225.04 |
SMILES Code : | O=C1NC=CC2=C1N=CC(Br)=C2 |
MDL No. : | MFCD22548037 |
InChI Key : | GUOAFNIATRDFCL-UHFFFAOYSA-N |
Pubchem ID : | 89500608 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 50.06 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.75 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.35 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.29 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.69 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.19 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.75 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.65 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.66 |
Solubility | 0.487 mg/ml ; 0.00216 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.85 |
Solubility | 3.17 mg/ml ; 0.0141 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.09 |
Solubility | 0.0181 mg/ml ; 0.0000804 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 |
-6.76 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 |
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) |
1.88 |
* 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 |
---|---|---|
2 g | With potassium tert-butylate; In tetrahydrofuran; for 3.0h;Reflux; | 5-Bromo-3-methyl-pyridine-2-carboxylic acid 1-dimethylamino-meth-(E)-ylideneamide (2.5 g, 9.25 mmol) was dissolved in THF (20 ml). KOtBu (1 .565 g, 13.05 mmol) in THF (30 ml) was added dropwise and the reaction mixture was heated to reflux for 3h and then cooled to rt.The pH was adjusted to 7 with concentrated HCI. The reaction mixture was concentrated.The brown solid obtained was titruated with water (10 ml). The solid thus obtained was collected by filtration (2 g, 8 mmol).HPLC: RtH9= 0.56 min; ESIMS [M+H]+ = 224.8, 226.8 (1 Br);1H-NMR (400 MHz, DMSO-d6): delta 1 1 .90 (s, 1 H), 8.85 (s, 1 H), 8.50 (s, 1 H), 7.43 (d, 1 H), 6.67(d, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.1 g | With N-ethyl-N,N-diisopropylamine; trichlorophosphate; In toluene; at 130.0℃; for 36.0h; | 3-Bromo-7H-[1 ,7]naphthyridin-8-one (1.5 g, 6.67 mmol) was suspended in toluene (20 ml). DIPEA (3.5 ml, 20 mmol) and POCI3 (1.8 ml, 20 mmol) were added and the reaction mixture was heated to 130 C for 36 h. The reaction mixture was cooled to rt and partitioned between water (75 ml) and EtOAc (150 ml). The phases were separated and the aq phase was extracted twice with EtOAc (25 ml). The combined organic layer was washed with NaHC03 solution and brine, treated with MgS04 and filtered. The filtrated was concentrated to give the desired product as a beige solid (1 .1 g, 4.52 mmol).HPLC: RtH9= 0.86 min; ESIMS [M+H]+ = 242.8, 244.8, 246.8 (1 Br,1 CI);1H-NMR (400 MHz, DMSO-d6): delta 9.22 (d, 1 H), 8.95 (2, 1 H), 8.49 (d, 1 H), 7.99 (d, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water; hydrogen bromide; In ethanol; for 4.0h;Reflux; | To a mixture of compound E2 (1.1 g, 4.4 mmol) in EtOH (9 mL) was added HBr (9 mL, 40% aq.) dropwise at room temperature. The mixture was stirred at reflux temperature for 4 h and cooled to room temperature. The precipitated solid was filtered and the filter cake was neutralized with sat. Na2C03 until the evolved gas ceased. Then the mixture was filtered and the filter cake was dried to give compound E3. MS (M+H+): 225. | |
With hydrogen bromide; In ethanol; water; for 4.0h;Reflux; | To a mixture of compound E2 (1.1 g, 4.4 mmol) in EtOH (9 mL) was added HBr (9 mL, 40% aq.) dropwise at room temperature. The mixture was stirred at reflux temperature for 4 h and cooled to room temperature. The precipitated solid was filtered and the filter cake wasneutralized with sat. Na2CO3 until the evolved gas ceased. Then the mixture was filtered and the filter cake was dried to give compound E3. MS (M+H): 225. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; In N,N-dimethyl-formamide; at 100.0℃; for 16.0h;Inert atmosphere; | A mixture of compound E3 (2.0 g, 8.89 mmol), sodium methanolate (2.40 g, 44.4 mmol) and copper(I) iodide (846 mg, 4.44 mmol) in DMF (20 mL) was stirred at 100 C for 16 h under N2. Then mixture was concentrated to give crude E4 which was used in the next step without further purification. | |
With copper(l) iodide; In N,N-dimethyl-formamide; at 100.0℃; for 16.0h;Inert atmosphere; | A mixture of compound E3 (2.0 g, 8.89 mmol), sodium methanolate (2.40 g, 44.4mmol) and copper(I) iodide (846 mg, 4.44 mmol) in DMF (20 mL) was stirred at 100 C for 16 hunder N2. Then mixture was concentrated to give cmde E4 which was used in the next stepwithout further purification. |
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