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Structure of 869885-60-9
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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. : | 869885-60-9 |
Formula : | C8H5ClO3S |
M.W : | 216.64 |
SMILES Code : | O=S(C1=CC=C(OC=C2)C2=C1)(Cl)=O |
MDL No. : | MFCD11053679 |
InChI Key : | DXQKXPTYOGEXEN-UHFFFAOYSA-N |
Pubchem ID : | 53403186 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P260-P280-P303+P361+P353-P301+P330+P331-P304+P340+P310-P305+P351+P338+P310 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅲ |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 49.3 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.66 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.86 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.35 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.44 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.0 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.82 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.09 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.11 |
Solubility | 0.168 mg/ml ; 0.000776 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.16 |
Solubility | 0.15 mg/ml ; 0.000694 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.83 |
Solubility | 0.0317 mg/ml ; 0.000146 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) |
Yes |
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 |
-5.95 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 |
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) |
2.55 |
* 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 |
---|---|---|
15% | Stage #1: With 2-iodo-propane; iodine; magnesium In tetrahydrofuran for 1 h; Heating / reflux Stage #2: With sulfuryl dichloride In tetrahydrofuran at -40 - -30℃; for 0.833333 h; |
Isopropyl iodide (15.0 mmol) was added dropwise to a suspension of iodine (0.12 mmol), magnesium (30.0 mmol) in tetrahydrofuran (25 mL). After 15 min, a solution of 5-bromobenzofuran (15.2 mmol) in tetrahydrofuran (25 mL) was added dropwise and the reaction mixture was heated at reflux for 1 h. The mixture was cooled to -30 °C and sulfonyl chloride was bubbled through the reaction mixture for 10 min. The mixture was maintained for 30 min whereupon sulfuryl chloride (15.1 mmol) was added dropwise while cooling to -30 to -40 °C. The resulting solution was maintained for an <n="135"/>additional 10 min and was allowed to warm to rt. The insoluble solids were removed by filtration and the filtrate was concentrated. The residue was diluted with dichloromethane (150 mL), washed with brine (3 x 100 mL), dried (sodium sulfate), and concentrated. The residue was purified by Flash chromatography (100/1 to 50/1 petroleum ether/ethyl acetate) to provide benzofuran-5-sulfonyl chloride in 15percent yield as a white solid. Data: 1H NMR (CDCl3) δ 8.37 (s, 1H), 8.00 (d, 1H), 7.84 (s, 1H), 7.44 (d, 1H), 6.97 (s, 1H). LC/MS (ES) m/z 286 [M+BnH-l]+. |
15% | Stage #1: With 2-iodo-propane; magnesium In tetrahydrofuranReflux Stage #2: With sulfur dioxide In tetrahydrofuran at -30℃; for 0.666667 h; Stage #3: With sulfuryl dichloride In tetrahydrofuran at -40 - 20℃; |
3. Synthesis of benzofuran-5-sulfonyl chloride.Isopropyl iodide (15.0 mmol) was added dropwise to a suspension of iodine (0.12 mmol), magnesium (30.0 mmol) in tetrahydrofuran (25 mL). After 15 min, a solution of 5- bromobenzofuran (15.2 mmol) in tetrahydrofuran (25 mL) was added dropwise and the reaction mixture was heated at reflux for 1 h. The mixture was cooled to -30 0C and sulfonyl chloride was bubbled through the reaction mixture for 10 min. The mixture was maintained for 30 min whereupon sulfuryl chloride (15.1 mmol) was added dropwise while cooling to -30 to -40 0C. The resulting solution was maintained for an additional 10 min and was allowed to warm to it. The insoluble solids were removed by filtration and the filtrate was concentrated. The residue was diluted with dichloromethane (150 mL), washed with brine (3 x 100 mL), dried (sodium sulfate), and concentrated. The residue was purified by Flash chromatography (100/1 to 50/1 petroleum ether/ethyl acetate) to provide benzofuran-5-sulfonyl chloride in 15percent yield as a white solid. Data: 1H NMR (CDCl3) δ 8.37 (s, IH), 8.00 (d, IH), 7.84 (s, IH), 7.44 (d, IH), 6.97 (s, IH). LC/MS (ES) m/z 286 [M+BnH-l]+. |
15% | Stage #1: With 2-iodo-propane; iodine; magnesium In tetrahydrofuranReflux Stage #2: With sulfur dioxide In tetrahydrofuran at -30℃; Stage #3: With sulfuryl dichloride In tetrahydrofuran at -40 - -30℃; |
3. Synthesis of benzofuran-5-sulfonyl chloride. Isopropyl iodide (15.0 mmol) was added dropwise to a suspension of iodine (0.12 mmol), magnesium (30.0 mmol) in tetrahydrofuran (25 mL). After 15 min, a solution of 5- bromobenzofuran (15.2 mmol) in tetrahydrofuran (25 mL) was added dropwise and the reaction mixture was heated at reflux for 1 h. The mixture was cooled to -30 0C and sulfonyl chloride was bubbled through the reaction mixture for 10 min. The mixture was maintained for 30 min whereupon sulfuryl chloride (15.1 mmol) was added dropwise while cooling to -30 to -40 0C. The resulting solution was maintained for an additional 10 min and was allowed to warm to rt. The insoluble solids were removed by filtration and the filtrate was concentrated. The residue was diluted with dichloromethane (150 mL), washed with brine (3 x 100 mL), dried (sodium sulfate), and concentrated. The residue was purified by Flash chromatography (100/1 to 50/1 petroleum ether/ethyl acetate) to provide benzofuran-5-sulfonyl chloride in 15percent yield as a white solid. Data: 1H NMR (CDCl3) δ 8.37 (s, IH), 8.00 (d, IH), 7.84 (s, IH), 7.44 (d, IH), 6.97 (s, IH). LC/MS (ES) m/z 286 [M+BnH-l]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With N-Bromosuccinimide In benzene at 80℃; for 1 h; | 2,3-Dihydrobenzofuran-5-sulfonyl chloride 300 mg (1.37 mmol) was dissolved in 2 mL of benzene. N-bromosuccinimide 244 mg (1.37 mmol) and AIBN 3 mg were added to the solution and the reaction was heated at 80° C. for 1 hour. The reaction was allowed to come to room temperature, filtered and the benzene removed under vacuum. The residue was purified by chromatography on silica gel with hexanes/methylene chloride=2/1 to afford 237 mg (80percent) of the pure material (TLC). The final product can be recrystallized from ether/hexanes to provide colorless crystals with m.p. 48.5-50.6° C.;Preparation of benzofuran-5-sulfonyl chloride 2,3-Dihydrobenzofuran-5-sulfonyl chloride 300 mg (1.37 mmol) was dissolved in 2 mL of benzene. N-bromosuccinimide 244 mg (1.37 mmol) and 3 mg AIBN were added to the solution and the reaction was heated at 80° C. for 1 hour. The reaction was allowed to come to room temperature, filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica gel (30percent CH2Cl2/hexanes) to afford 237 mg (80percent yield) of the pure material. 3-Methyl-2,3-dihydrobenzofuran was synthesised as described in the literature starting from 2-iodophenol (Organic Synthesis, CV3, 418; L. W. Menapace and H. G. Kuivila, J. Amer. Chem. Soc., 86, 3047 (1964), and references cited therein). |
80% | With N-Bromosuccinimide In benzene at 80℃; for 1 h; | Benzofuran-5-sulfonyl chloride; 2,3-Dihydrobenzofuran-5-sulfonyl chloride 300 mg (1.37 mmol) was dissolved in 2 mL of benzene. N-bromosuccinimide 244 mg (1.37 mmol) and AIBN 3 mg were added to the solution and the reaction was heated at 80° C. for 1 hour. The reaction was allowed to come to room temperature, filtered and the benzene removed under vacuum. The residue was purified by chromatography on silica gel with hexanes/methylene chloride=2/1 to afford 237 mg (80percent) of the pure material (TLC). The final product can be recrystallized from ether/hexanes to provide colorless crystals with m.p. 48.5-50.6° C. |
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