Structure of 343262-51-1
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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. : | 343262-51-1 |
Formula : | C6H6BrNO2S |
M.W : | 236.09 |
SMILES Code : | O=S(C1=CN=C(Br)C=C1)(C)=O |
MDL No. : | MFCD04974509 |
InChI Key : | ZRXQHWYUAIXKRL-UHFFFAOYSA-N |
Pubchem ID : | 9899483 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 45.03 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.41 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.31 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.11 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.33 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.68 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.34 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.35 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.34 |
Solubility | 1.08 mg/ml ; 0.00456 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.87 |
Solubility | 3.21 mg/ml ; 0.0136 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.2 |
Solubility | 0.15 mg/ml ; 0.000637 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 |
-6.95 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) |
2.4 |
* 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 |
---|---|---|
96% | With sodium sulfate; 3-chloro-benzenecarboperoxoic acid; In dichloromethane; | 5-Methylsulfonyl-2-bromopyridine. (step 2) To a solution of 5-methylthio-2-bromopyridine from step 1 (18.9 g, 0.093 mol) in methylene chloride (600 mL), m-chloroperbenzoic acid (48 g, 0.19 mol) was added portionwise at 0 C. and the mixture was stirred for 2 hours at room temperature. Aqueous saturated Na2SO3 (200 mL) was added and stirred for 15 minutes and organic phase was separated and washed with aqueous saturated sodium bicarbonate (NaHCO3) (200 mL), dried over magnesium sulfate (MgSO4), and concentrated in vacuo gave the title compound (20.9 g, 96%). 1H-NMR (CDCl3) δ: 8.91 (d, J=2.6 Hz, 1H), 8.06 (dd, J =2.6, 8.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 1H), 3.12 (s, 3H). |
96% | With sodium sulfate; 3-chloro-benzenecarboperoxoic acid; In dichloromethane; | 5-Methylsulfonyl-2-bromopyridine. (step 2) To a solution of 5-methylthio-2-bromopyridine from step 1 (18.9 g, 0.093 mol) in methylene chloride (600 mL), m-chloroperbenzoic acid (48 g, 0.19 mol) was added portionwise at 0 C. and the mixture was stirred for 2 hours at room temperature. Aqueous saturated Na2SO3 (200 mL) was added and stirred for 15 minutes and organic phase was separated and washed with aqueous saturated sodium bicarbonate (NaHCO3) (200 mL), dried over magnesium sulfate (MgSO4), and concentrated in vacuo gave the title compound (20.9 g, 96%). 1H-NMR (CDCl3) δ: 8.91 (d, J=2.6 Hz, 1H), 8.06 (dd, J=2.6, 8.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 1H), 3.12 (s, 3H). |
71% | With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 0 - 20℃; for 2h; | Intermediate 21; 2-Bromo-5-mcthancsulfonylpyridinc; To a solution of <strong>[134872-23-4]2-bromo-5-methylsulfanylpyridine</strong> (1.53g, 7.6 mmol) in DCM (2OmL) at 0 0C was added wCPBA (3.95g, 15.95 mmol) portionwise. The mixture was allowed to warm to rt and stir for 2h. DCM (30ml) was added and the organics washed with saturated Na2SO3 solution, saturated Na2CO3 solution, dried (MgSO4) and the solvent removed in vacuo. The crude product was triturated with Et2O, filtered and dried in vacuo to afford the title compound (1.25g, 71%): δϖ (CDCl3) 3.15 (3H, s), 7.75 (IH, d), 8.08 (IH, dd), 8.95 (IH, d). |
With Oxone; In tetrahydrofuran; water; at 0 - 20℃; for 3h;Inert atmosphere; | 174> Preparation Example 9:Synthesis of 2-bromo-5-methanesulfonyl -pyridine<i76> Under a nitrogen atmosphere, in a 500ml flask, 5g of 5-methylthio~2- bromopyr idine was added in THF 200mL/dist i 1 led water 40mL, and stirred. At 0 C 40g of oxone was added thereto, followed by stirring at room temperature for 3 hours. Then, the reaction mixture was filtered, and the filtrate was extracted with 200ml of distilled water and 200ml of ethyl acetate. The organic layer was dried with anhydrous magnesium sulfate, and vacuum-dried so as to provide a target compound.<i77> ¾ NMR (400MHz, CDC13): 8.93(1H, s), 8.06-8.09UH, d), 7.73-7.75UH, d) ,3.14C3H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; | STEP 2 5-Methylsulfonyl-2-bromopyridine To a solution of 5-methylthio-2-bromopyridine from step 1 (18.9 g, 0.093 mol) in methylene chloride (600 mL), was added portionwise m-chloroperbenzoic acid (48 g, 0.19 mol) at 0 C. and the mixture was stirred for 2 hours at room temperature. Aqueous saturated sodium sulfate (Na2SO3) (200 mL) was added and stirred for 15 minutes and organic phase was separated and washed with aqueous saturated sodium bicarbonate (NaHCO3) (200 mL), dried over MgSO4, and concentrated in vacuo gave the title compound (20.9g, 96%). 1H-NMR (CDCl3) δ: 8.91 (d, J=2.6 Hz, 1H), 8.06 (dd, J=2.6, 8.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 1H), 3.12 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; In tetrahydrofuran;Reflux; Sealed tube; | Step A: tert-butyl 2-(5-(methylsulfonyl)pyridin-2-yl)-2,9-diazaspiro[5 .Slundecane-9- carboxylate: To a microwave vial was charged with tert-butyl 2,9-diazaspiro[5.5]undecane-9- carboxylate (100 mg, 0.39 mmol), 2-bromo-5-(methylsulfonyl)pyridine (102 mg, 0.43 mmol), Pd2(dba)3 (18 mg, 0.020 mmol), S-Phos (32 mg, 0.079 mmol), and Cs2CO3 (380 mg, 1.2 mmol). The vial was sealed, degassed, and filled with THF (2000 tl). The reaction mixture was refluxedovernight, diluted with water, extracted with EtOAc, washed with brined, dried, evaporated to give the crude product, which was purified by column chromatography (0-100% EtOAc/hex) to give tert-butyl 2-(5 -(methylsulfonyl)pyridin-2-yl)-2,9-diazaspiro [5.5 ]undecane-9-carboxylate as a white solid. LCMS: m/z 410 (M+H). |
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