Structure of 406233-31-6
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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. : | 406233-31-6 |
Formula : | C6H5FN2O4S |
M.W : | 220.18 |
SMILES Code : | FC1=C(C=C(C=C1)[S](=O)(=O)N)[N+](=O)[O-] |
MDL No. : | MFCD08703185 |
Boiling Point : | No data available |
InChI Key : | FAYVDRRKPVJSPE-UHFFFAOYSA-N |
Pubchem ID : | 16782487 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 46.22 |
TPSA ? Topological Polar Surface Area: Calculated from |
114.36 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.81 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.13 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.88 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.29 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.63 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.18 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.47 |
Solubility | 7.42 mg/ml ; 0.0337 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.09 |
Solubility | 1.8 mg/ml ; 0.00817 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.63 |
Solubility | 5.15 mg/ml ; 0.0234 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) |
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 |
-7.55 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 |
2.0 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) |
2.29 |
* 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 |
---|---|---|
84% | With triethylamine; In 1,4-dioxane;Heating / reflux; | A solution of intermediate h (2.5g, 8.9 mmol) and intermediate i (1.96g, 8.9 mmol) in 100 ml of dioxane was treated with Et3N (1.8g, 17.8mmol) heated to reflux overnight, concentrated, and purified by silica gel chromatography eluting with PE:EA=(1 :1) to provide the desired product] (3.6g, yield:84%) . MS (ESI) m/e (M-I-H+): 481; 1H-NMR (DMSO, 400 MHz): delta 8.66 (d, J = 9.6 Hz, IH), 8.35 (s, IH), 7.69 (d, J = 8.8 Hz, IH), <n="35"/>7.41-7.21 (m, 5H), 7.15 (m, IH), 7.05 (d, J= 9.6 Hz, IH), 4.39 (m, IH), 3.52-3.36 (m, 10H), 2.96 (m, IH), 2.76 (m, IH). |
83% | With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 50℃;Inert atmosphere; | To a solution of <strong>[870812-94-5](R)-3-amino-1-morpholino-4-(phenylthio)butan-1-one</strong> (INTERMEDIATE 72, 375.5 mg, 1.34 mmol) in DMF (2.5 ml) and DIPEA (1.20 Ml, 6.87 mmol) was added 4-fluoro-3-nitrobenzenesulfonamide (INTERMEDIATE 18, 325.8 mg, 1.48 mmol), and the resulting dark solution was stirred at 50 C. overnight, under a nitrogen atmosphere. The mixture was diluted with EtOAc (50 ml) and washed with water and brine (30 ml each), dried (Na2SO4), filtered, and evaporated under reduced pressure. The concentrate was purified by column chromatography (ISCO, 40 g silica gel column, eluting with 0?100% EtOAc/DCM) to give the title product (532.5 mg, yield: 83%).1H NMR (400 MHz, DICHLOROMETHANE-d2) delta ppm 2.72 (dd, 1H) 2.85-2.97 (m, 1H) 3.25-3.44 (m, 4H) 3.48-3.68 (m, 6H) 4.26-4.39 (m, 1H) 4.96 (s, 2H) 6.76 (d, 1H) 7.23-7.37 (m, 3H) 7.37-7.46 (m, 2H) 7.74 (dd, 1H) 8.61 (d, 1H) 9.08 (d, 1H).LCMS: (ESI) m/z 481 [M+H]+.Optical Rotation:Concentration: 0.1 g/dLLamp: SodiumWavelength: 589 nmTemperature: 20 C.Path length: 10 cm Cell volume: 1 ml Solvent: CH2Cl2 [alpha]=-212 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Butyl-6-hydroxy-2-azaspiro [3.3] heptane-2-carboxylic acid tert-butyl ester (0.21 g, 0.98 mmol, 1.0 eq)Was added to anhydrous THF (10 mL), then NaH (50 mg, 1.25 mmol, 1.3 eq) was added, reacted at room temperature for half an hour, and then 4-fluoro-3-nitro-benzenesulfonamide (0.41 g, 0.98 mmol, 1.0 eq) in THF (5 mL)After the reaction at room temperature for 6 h,The reaction was poured into water (20 mL) and extracted with EA (15 mL x 2). The organic phase was dried over anhydrous sodium sulfate and spin dried to give a yellow solid which was beaten with 5 mL DCM and 20 mL PE. And then filtered, the yellow solid product 0.39g, the yield of 100percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(0556) To a solution of <strong>[199174-24-8](S)-tert-butyl 3-(hydroxymethyl)pyrrolidine-1-carboxylate</strong> (0.300 g) in tetrahydrofuran (5 ml) was added sodium hydride (0.238 g). After stirring for 15 minutes, 4-fluoro-3-nitrobenzenesulfonamide (0.295 g) was added and reaction stirred at room temperature. After 1 hour, the reaction was partitioned between water (25 ml) and dichloromethane (50 ml) and the reaction quenched with 1N aqueous HCl (5.96 ml). The organic layer was separated, dried over magnesium sulfate, filtered, and concentrated. Silica gel chromatography (Reveleris 12 g) eluting with a gradient of 0.2% to 2% methanol/dichloromethane over 30 minutes (flow=36 m/minute) gave the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With triethylamine; In tetrahydrofuran; at 20℃; for 16h; | To a stirred solution of /er/-butyl 4-(aminomethyl)-4- fluoropiperidine-l-carboxylate (2.00 g, 8.61 mmol) in THF (30 mL), was added 4-fluoro-3- nitrobenzenesulfonamide (2.08 g, 9.47 mmol) followed by triethylamine (4.8 mL, 34.45 mmol). The resulting reaction mixture was stirred at rt for 16 h. The reaction was then concentrated, and the resulting residue was diluted with 10% MeOH-DCM (50 mL) and washed with ice-cold water (5 x 50 mL). The organic layer was dried over Na2S04. filtered and concentrated. The crude product was purified by trituration with Et20 to afford /er/-butyl 4-fluoro-4-(((2-nitro-4-sulfamoylphenyl)amino)methyl)piperidine-l-carboxylate (Intermediate 15-1) (1.6 g, 43% yield). LC/MS (ESI) m/z 333.10 [M -C5H9C>2+H]+. |
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