Structure of 337463-88-4
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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. : | 337463-88-4 |
Formula : | C7H5BrN2O2 |
M.W : | 229.03 |
SMILES Code : | BrC1=CC=C2OCC(=O)NC2=N1 |
MDL No. : | MFCD11101028 |
InChI Key : | GDVHYNCHZKTTSQ-UHFFFAOYSA-N |
Pubchem ID : | 21873772 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 48.76 |
TPSA ? Topological Polar Surface Area: Calculated from |
51.22 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.69 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.16 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.6 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.51 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.7 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.13 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.36 |
Solubility | 0.998 mg/ml ; 0.00436 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.83 |
Solubility | 3.38 mg/ml ; 0.0148 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.12 |
Solubility | 0.175 mg/ml ; 0.000766 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) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.87 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 |
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) |
2.36 |
* 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 |
---|---|---|
100% | Step 4 To a solution of Compound (9) (3.12 g, 13.7 mmol) in tetrahydrofuran (50 mL), borane-tetrahydrofuran complex (33 mL, 33.0 mmol) was added at room temperature. The solution was then stirred at 90C for 1.5 hours. Methanol (2.0 mL) was added to the reaction solution, and then the mixture was stirred at 90C for 20 minutes. The reaction solution was concentrated in vacuo. The residue was dissolved in ethyl acetate, washed with aqueous saturated sodium bicarbonate, dried with anhydrous magnesium sulfate, and then concentrated in vacuo to yield subject compound (10) (3.17 g, 100%) as a yellow powder.1H-NMR (DMSO-d6) 57.04 (1H, br s), 6.69 (1H, d, J = 7.8 Hz), 6.40 (1H, d, J = 7.8 Hz), 3.91 (2H, t, J = 4.2Hz), 3.19-3.23 (2H, m) LC/MS (Method A): 1.44 min, [M+H]+ = 215.2. | |
99% | With diborane; In tetrahydrofuran; for 1h;Cooling with ice; Reflux; | Under ice bath conditions, Borane in tetrahydrofuran (5.5 mL, 5.5 mmol, 1.0 M) Add dropwise to compound 3.2 (500 mg, 2.19 mmol) In a solution of tetrahydrofuran (25 mL), The reaction system was stirred under reflux with heating for 1 hour. The reaction was then carefully quenched with methanol (10 drops) under reflux. The mixture was cooled to room temperature and concentrated under reduced pressure to remove solvent. The residue was chromatographed on silica gel ( petroleum ether / ethyl acetate = 5/1) Purification afforded compound 23.1 (470 mg, yield: 99%) It is a white solid. |
87% | With dimethylsulfide borane complex; potassium carbonate; In tetrahydrofuran; at 70℃; for 0.25h;Inert atmosphere; | Part IV- Synthesis of 6-Bromo-3,4-dihydro-2H-pyrido[3,2-b] [1,4]oxazine; 6-Bromo-4H-pyrido[3,2-b][1,4]oxazin-3-one (1.35 g, 5.89 mmol) was dissolved inTHF (40 mL). Boranedimethylsulphide complex (2.0 Min THF, 5.89 mL, 11.79 mmol) wasadded and the resulting mixture heated to 70 C under nitrogen for 15 minutes. Next, thereaction mixture was cooled to room temperature, quenched with methanol ( ~5 mL ), and then dried under vacuum to obtain a white solid. The crude material was dissolved indichloromethane and washed with H20. The aqueous phase was discarded and the organicphase was dried under vacuum to give 6-bromo-3,4-dihydro-2H-pyrido[3,2-b ][1,4]oxazine.Yield: 1.1 g (87%). LCMS (ESI): calc. C7H7BrN20 = 214, 216; obs. M+H = 215, 217. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 100℃; | Compound 3.2 (1.9 g, 8.29 mmol),<strong>[955368-90-8]2-allyl-6-(methylthio)-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one</strong> (1.84 g, 8.29 mmol),Cuprous iodide (1.5 g, 8.29 mmol),Anhydrous potassium carbonate (2.35 g, 17 mmol)And N,N-dimethylethylenediamine (0.73g, 8.29mmol)Add to 1,4-dioxane (30 mL),The reaction system was stirred at 100 C overnight.Cool to room temperature,Filter the reaction solution,The filtrate is concentrated,The residue was purified by silica gel column chromatography (EtOAc /EtOAcCompound 3-1 (1.56 g, yield: 51%) was obtained as a yellow solid. |
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