Structure of 6269-91-6
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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. : | 6269-91-6 |
Formula : | C7H8N2O4S |
M.W : | 216.21 |
SMILES Code : | O=S(C1=CC([N+]([O-])=O)=CC=C1C)(N)=O |
MDL No. : | MFCD00115503 |
InChI Key : | CLXWMMGXFSZUNP-UHFFFAOYSA-N |
Pubchem ID : | 234282 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 51.22 |
TPSA ? Topological Polar Surface Area: Calculated from |
114.36 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.75 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.68 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.63 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.39 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.68 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.2 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.79 |
Solubility | 3.47 mg/ml ; 0.0161 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.66 |
Solubility | 0.475 mg/ml ; 0.0022 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.74 |
Solubility | 3.94 mg/ml ; 0.0182 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 |
-7.14 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) |
2.23 |
* 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 |
---|---|---|
With hydrogenchloride; tin(ll) chloride; In diethylene glycol dimethyl ether; water; for 0.75h; | To a stirred solution of 2-methyl-5-nitrobenzenesulfonamide (4.6 g, 0.021 mol) in 2-methoxyethyl ether (43 mL), at [0] C, was added a solution of 16.1 g [OF TIN (II)] chloride in 32 mL of concentrated HCI dropwise over 15 min. After the addition was complete, the ice bath was removed and the solution was allowed to stir for an additional 30 min. Approximately 130 mL of diethyl ether was added to reaction. The mixture was stirred vigorously for 1 h. The mixture was basified with a solution of [NAOH] and [NAHCO3,] and extracted with ethyl acetate (x 3). The combined ethyl acetate layers were dried over anhydrous [MGS04,] filtered and concentrated to give crude product. Trituation of the crude product with methanol provided 2.4 g of pure [5-AMINO-2-METHYLBENZENESULFONAMIDE] as light brown [SOLID.APOS;H] NMR (300 MHz, DMSO-d6) [# 7.11-7. ] 10 (m, 3H), 6.95 (d, J = 8. 1 Hz, [1 H),] 6.60 (dd, J = 8.1 [# 2.4 HZ, 1H),] 5.24 (s, 2H), 2.36 (s, 3H). MS [(ES+,] m/z) 187 (M+H). | |
With hydrogen;palladium 10% on activated carbon; In methanol; dichloromethane; under 2585.81 Torr; for 0.25h; | To a solution of 3-aminosulfonyl-4-methylnitrobenzene in dichloromethane and methanol was added 10percent Pd/C and the mixture shaken under a hydrogen atmosphere at 50 psi for 15 minutes. The mixture was filtered through diatomaceous earth and the filter cake was washed with methanol. The combined organic solvents were concentrated under reduced pressure to give crude product, which was further purified by flash column chromatography (ethyl acetate:hexanes 1:1) to give 3-aminosulfonyl-4-methylaniline, LCMS: purity: 87percent; MS (m/e): 187 (MH+). | |
palladium-carbon; In methanol; dichloromethane; | To a solution of 3-aminosulfonyl-4-methylnitrobenzene in dichloromethane and methanol was added 10percent Pd/C and the mixture shaken under a hydrogen atmosphere at 50 psi for 15 minutes.The mixture was filtered through diatomaceous earth and the filter cake was washed with methanol.The combined organic solvents were concentrated under reduced pressure to give crude product, which was further purified by flash column chromatography (ethyl acetate:hexanes 1:1) to give 3-aminosulfonyl-4-methylaniline, LCMS: purity: 87percent; MS (m/e): 187 (MH+). |
With palladium 10% on activated carbon; hydrogen; In methanol; dichloromethane; under 2585.81 Torr; for 0.25h; | To a solution of 3-aminosulfonyl-4-methylnitrobenzene in dichloromethane and methanol was added 10percent Pd/C and the mixture shaken under a hydrogen atmosphere at 50 psi for 15 minutes. The mixture was filtered through diatomaceous earth and the filter cake was washed with methanol. The combined organic solvents were concentrated under reduced pressure to give crude product, which was further purified by flash column chromatography (ethyl acetate:hexanes 1:1) to give 3-aminosulfonyl-4-methylaniline, LCMS: purity: 87percent; MS (m/e): 187 (MH+). | |
With palladium 10% on activated carbon; hydrogen; In methanol; dichloromethane; under 2585.81 Torr; for 0.25h; | To a solution of 3-aminosulfonyl-4-methylnitrobenzene in dichloromethane and methanol was added 10percent Pd/C and the mixture shaken under a hydrogen atmosphere at 50 psi for 15 minutes. The mixture was filtered through diatomaceous earth and the filter cake was washed with methanol. The combined organic solvents were concentrated under reduced pressure to give crude product, which was further purified by flash column chromatography (ethyl acetate:hexanes 1:1) to give 3-aminosulfonyl-4-methylaniline, LCMS: purity: 87percent; MS (m/e): 187 (M+). | |
With palladium 10% on activated carbon; hydrogen; In methanol; dichloromethane; under 2585.81 Torr; for 0.25h; | To a solution of 3-aminosulfonyl-4-methylnitrobenzene in dichloromethane and methanol was added 10 percentPd/C and the mixture shaken under a hydrogen atmosphere at 50 psi for 15 minutes. The mixture was filtered throughdiatomaceous earth and the filter cake was washed with methanol. The combined organic solvents were concentratedunder reduced pressure to give crude product, which was further purified by flash column chromatography (ethyl acetate:hexanes 1:1) to give 3-aminosulfonyl-4-methylaniline, LCMS: purity: 87percent; MS (m/e): 187 (MH+). | |
To a stirred solution of 2-methyl-5-nitrobenzenesulfonamide (4.6 g, 0.021 mol) in 2-methoxyethyl ether (43 mL), at 0° C., was added a solution of 16.1 g of tin(II) chloride in 32 mL of concentrated HCl dropwise over 15 min. After the addition was complete, the ice bath was removed and the solution was allowed to stir for an additional 30 min. Approximately 130 mL of diethyl ether was added to reaction. The mixture was stirred vigorously for 1 h. The mixture was basified with a solution of NaOH and NaHCO3, and extracted with ethyl acetate (*3). The combined ethyl acetate layers were dried over anhydrous MgSO4, filtered and concentrated to give crude product. Trituation of the crude product with methanol provided 2.4 g of pure 5-amino-2-methylbenzenesulfonamide as light brown solid. 1H NMR (300 MHz, DMSO-d6) delta 7.11-7.10 (m, 3H), 6.95 (d, J=8.1 Hz, 1H), 6.60 (dd, J=8.1 and 2.4 Hz, 1H), 5.24 (s, 2H), 2.36 (s, 3H). MS (ES+, m/z) 187 (M+H). | ||
With hydrogenchloride; tin(ll) chloride; In diethyl ether; diethylene glycol dimethyl ether; water; at 0℃; for 1.75h; | Intermediate Example 5 Preparation of 5-amino-2-methylbenzenesulfonamide Procedure 1 To a stirred solution of 2-methyl-5-nitrobenzenesulfonamide (4.6 g, 0.021 mol) in 2-methoxyethyl ether (43 mL), at 0 °C, was added a solution of 16.1 g of tin(II) chloride in 32 mL of concentrated HCI dropwise over 15 min. After the addition was complete, the ice bath was removed and the solution was allowed to stir for an additional 30 min. Approximately 130 mL of diethyl ether was added to reaction. The mixture was stirred vigorously for 1 h. The mixture was basified with a solution of NaOH and NaHC03, and extracted with ethyl acetate (x 3). The combined ethyl acetate layers were dried over anhydrous MgS04, filtered and concentrated to give crude product. Trituation of the crude product with methanol provided 2.4 g of pure 5-amino-2- methylbenzenesulfonamide as light brown solid. |
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