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Structure of 49584-26-1
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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. : | 49584-26-1 |
Formula : | C7H4ClNO2S |
M.W : | 201.63 |
SMILES Code : | C1=CC(=CC=C1[S](=O)(=O)Cl)C#N |
MDL No. : | MFCD00052337 |
InChI Key : | DBMFYTQPPBBKHI-UHFFFAOYSA-N |
Pubchem ID : | 39497 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H314-H317 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅲ |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 44.24 |
TPSA ? Topological Polar Surface Area: Calculated from |
66.31 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.46 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.69 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.57 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.29 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.58 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.46 |
Solubility | 0.701 mg/ml ; 0.00348 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.7 |
Solubility | 0.405 mg/ml ; 0.00201 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.03 |
Solubility | 0.188 mg/ml ; 0.000933 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 |
-6.33 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) |
1.76 |
* 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 |
---|---|---|
Example 24 4-Cyano-N-(5-chloroquinolin-2-yl)-benzenesulfonamide The title compound was obtained from 3-amino-8-bromoquinoline (Preparation Example 2) and 4-cyanobenzenesulfonyl chloride by the procedure of Example 1. 1H-NMR (CDCl3) delta (ppm): 6.96 (1H, d, J=9.5 Hz), 7.35 (1H, d, J=8.7 Hz), 7.45 (1H, d, J=8.7 Hz), 7.57 (1H, t, J=8.7 Hz), 7.78 (2H, d, J=8.9 Hz), 8.10 (2H, d, J=8.9 Hz), 8.33 (1H, d, J=9.5 Hz). | ||
Synthetic Example 24b 4-Cyano-N-(5-chloroquinoline-2-yl)-benzenesulfonamide The title compound was obtained from 3-amino-8-bromoquinoline (Production Example 2b) and 4-cyanobenzenesulfonyl chloride in the same manner as in Synthetic Example 1b. 1H-NMR(CDCl3) delta (ppm): 6.96(1H, d, J=9.5Hz), 7.35(1H, d,J=8.7Hz), 7.45(1H, d, J=8.7Hz), 7.57(1H, t J=8.7Hz), 7.78(2H, d, J=8.9Hz), 8.10(2H, d, J=8.9Hz), 8.33(1H, d, J=9.5Hz). | ||
SYNTHETIC EXAMPLE 24b 4-Cyano-N-(5-chloroquinoline-2-yl) -benzenesulfonamide The title compound was obtained from 3-amino-8-bromoquinoline (Production Example 2b) and 4-cyanobenzenesulfonyl chloride in the same manner as in Synthetic Example 1b. 1H-NMR(CDCl3) delta (ppm): 6.96(1H, d, J=9.5 Hz), 7.35(1H, d, J=8.7 Hz), 7.45(1H, d, J=8.7 Hz), 7.57(1H, tJ=8.7 Hz), 7.78(2H, d, J=8.9 Hz), 8.10(2H, d, J=8.9 Hz), 8.33(1H, d, J=9.5 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Reference Example 243 4-[2-(2-Fluorophenyl)-4-formyl-1H-pyrrol-1-yl]sulfonyl}benzonitrile To a solution (28 mL) of <strong>[881674-56-2]5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde</strong> (284 mg) in tetrahydrofuran was added sodium hydride (60% in oil, 181 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (992 mg) was added dropwise and the mixture was stirred for 30 min, (4-cyanobenzene)sulfonyl chloride (606 mg) was added, and the mixture was further stirred for 1 hr. Saturated brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=4:1?2:3) to give the title compound as colorless crystals (yield 420 mg, 79%). 1H-NMR (CDCl3)delta: 6.69 (1H, d, J=1.8 Hz), 6.98-7.04 (1H, m), 7.16-7.18 (2H, m), 7.42-7.49 (1H, m), 7.51-7.54 (2H, m), 7.67-7.71 (2H, m), 8.12 (1H, d, J=1.8 Hz), 9.90 (1H, s). | |
In tetrahydrofuran; | Reference Example 243 4-[2-(2-Fluorophenyl)-4-formyl-1H-pyrrol-1-yl]sulfonyl}benzonitrile To a solution (28 mL) of <strong>[881674-56-2]5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde</strong> (284 mg) in tetrahydrofuran was added sodium hydride (60% in oil, 181 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (992 mg) was added dropwise and the mixture was stirred for 30 min, (4-cyanobenzene)sulfonyl chloride (606 mg) was added, and the mixture was further stirred for 1 hr. Saturated brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=4:1?2:3) to give the title compound as colorless crystals (yield 420 mg, 79%). 1H-NMR (CDCl3)delta: 6.69 (1H, d, J=1.8 Hz), 6.98-7.04 (1H, m), 7.16-7.18 (2H, m), 7.42-7.49 (1H, m), 7.51-7.54 (2H, m), 7.67-7.71 (2H, m), 8.12 (1H, d, J=1.8 Hz), 9.90 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; | To a solution of 1 ,1-dimethylethyl 2-ethyl-1-piperazinecarboxylate (100mg, 0.467 mmol) in DCM (5ml_) was added di-isopropylethylamine (0.253mL, 1.447 mmol), followed by gradual addition of 4-cyanobenzenesulfonyl chloride (103mg, 0.513 mmol). The reaction mixture was allowed to stir for 1 hour. The reaction mixture was diluted with DCM (1 OmL) and the solution was washed with saturated aqueous sodium bicarbonate solution (1OmL, twice), then with distilled water (1OmL). The organic layer was dried (MgSO4), filtered and reduced in vacuo to yield 1 ,1-dimethylethyl 4-[(4-cyanophenyl)sulfonyl]-2-ethyl-1-piperazinecarboxylate as a crude transparent oil (173mg), MS ES+ve m/z 280 (M+H-100). To 1 ,1-dimethylethyl 4-[(4-cyanophenyl)sulfonyl]-2-ethyl-1-piperazinecarboxylate (173mg, 0.456 mmol) was added hydrogen chloride 1 M solution in 1 ,4 dioxane (1OmL) solution, followed by the addition of 3 drops of water. The reaction mixture was allowed to stir for 14hours. After this time, 5M aqueous HCI (1 ml) was added and the mixture was stirred for 12hours. The reaction mixture was concentrated in vacuo to yield colourless oil. The colourless oil was dissolved in methanol (1 OmL) and passed down a SCX-2 column washing with two column volumes of methanol and eluting the product with 2N ammonia solution in methanol (three column volumes). The fraction containing eluted product was reduced in vacuo to yield 4-[(3-ethyl-1- piperazinyl)sulfonyl]benzonitrile (99mg) as a transparent oil, MS ES+ve m/z 280 (M+H).To a solution of 4-[(3-ethyl-1-piperazinyl)sulfonyl]benzonitrile (99mg, 0.354mol) in tetrahydrofuran (1OmL) was added triethylamine (0.074mL, 0.532mmol) followed by drop wise addition of benzoyl chloride (0.045mL, 0.390mmol). The reaction mixture was allowed to stir for 30minut.es. The reaction mixture was diluted with DCM (1 OmL) and the solution was washed with saturated aqueous sodium bicarbonate solution (1OmL, twice), then 0.1 M hydrochloric acid (1OmL). The organic layer was dried with (MgSO4), filtered and concentrated in vacuo to yield 144mg colourless oil. The oil was dissolved in minimum volume of hot ethyl acetate (~2ml), hot iso-hexane (10ml) was then added and allowed to cool to room temperature. The supernatant was decanted off, and residual solid triturated with diethyl ether (50ml), to yield a white solid (67mg, 37%).1H-NMR (CDCI3) delta 0.65-1.19 (3H, br m), 1.78-1.98 (2H, m), 2.20-2.40 (1 H, m), 2.40- 2.57 (1 H, m), 2.96-3.48 (1 H, m), 3.48-3.96 (3H, m), 4.21-5.01 (1 H, m), 7.28-7.31 (2H, m), 7.36-7.45 (3H, m), 7.81-7.89 (4H, m).MS ES+ve m/z 384 (M+H).The single enantiomers were isolated from the racemic 4-[3-ethyl-4-(phenylcarbonyl)-1-piperazinyl]sulfonyl}benzonitrile (53mg) via chiral preparative chromatography using the following conditions:- Column: Chiralpak IC (20mm x 250mm, 5mum)- Eluent: Heptane: Ethanol 50:50 v/v pump-mixed - Flow rate =17. Omls/min- U.V. Absorbance (S) 215nm- Autosampler injection (250mul of sample in 20%Heptane/30%EtOH/50%DMF on column)- lsocratic Run time = 30 minutesIsolated enantiomers were analysed via chiral analytical chromatography using the following conditions:- Chiralpak IC (4.6mm x 250mm, 5mum)- Heptane: Ethanol 50:50 v/v pump-mixed - Flow rate =1. Omls/min- U.V. Absorbance (at) 215nm- Autosampler injection (1 Omul of sample in mobile phase on column)- lsocratic Run time = 30 minutesIsolated compounds: Example 5a: Faster running enantiomer (4-[(3S)-3-ethyl-4-(phenylcarbonyl)-1- piperazinyl]sulfonyl}benzonitrile or 4-[(3R)-3-ethyl-4-(phenylcarbonyl)-1- piperazinyl]sulfonyl}benzonitrile, 16mg)Retention time 19.37min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.7% | With triethylamine; In tetrahydrofuran; at 10 - 35℃; for 16h; | (Step 1) To a solution of <strong>[480452-05-9]tert-butyl (3-amino-2-methylpropyl)carbamate</strong> (200 mg, 1.06 mmol) and TEA (0.444 mL, 3.19 mmol) in THF (5 mL) was added 4-cyanobenzene-1-sulfonyl chloride (214 mg, 1.06 mmol), and the mixture was stirred at room temperature for 16 hr. To the reaction solution was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 10 to 100% ethyl acetate/hexane) to give tert-butyl (3-(4-cyanophenylsulfonamido)-2-methylpropyl)carbamate (273 mg, 0.772 mmol, 72.7%) as a white powder. 1H-NMR (300MHz, DMSO-d6) :delta0.77(3H,d,J=6.8Hz), 1.34(9H,s), 1.53-1.71(1H,m), 2.52-2.57(1H,m), 2.64-2.89(3H,m), 6.78(1H,t,J=5.8Hz), 7.84(1H,s), 7.90-7.97(2H,m), 8.05-8.12(2H,m) |
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