Structure of 42137-88-2
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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. : | 42137-88-2 |
Formula : | C11H15Cl2NO2S |
M.W : | 296.21 |
SMILES Code : | O=S(C1=CC=C(C)C=C1)(N(CCCl)CCCl)=O |
MDL No. : | MFCD00018944 |
InChI Key : | PTVBBIMKLOMGSY-UHFFFAOYSA-N |
Pubchem ID : | 96039 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.45 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 71.41 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.76 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.37 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.62 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.54 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.43 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.5 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.69 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.19 |
Solubility | 0.19 mg/ml ; 0.000642 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.23 |
Solubility | 0.174 mg/ml ; 0.000588 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.89 |
Solubility | 0.00383 mg/ml ; 0.0000129 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
-6.25 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.46 |
* 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 sodium amide; In tetrahydrofuran; at 0 - 60℃; for 3h; | 2-Fluorobenzyl cyanide (Tokyo Chemical Industry CO., LTD., 0.99 g) was dissolved in tetrahydrofuran (18 ml) and the mixture was cooled to 0C. Sodium amide (550 mg) and the compound (1.91 g) of Starting Material Synthetic Example 24 were added, and the mixture was stirred with heating at 60C for 3 hr. After completion of the reaction, a saturated aqueous ammonium chloride solution was added, and the mixture was extracted with diethyl ether. The organic layer was dried and the solvent was evaporated under reduced pressure. The resulting solid was washed in a suspension state with diethyl ether. A hydrobromide saturated acetic acid solution (5 ml) was added to the intermediate, and the mixture was stirred at 80C for 5 hr. The reaction mixture was cooled to room temperature. The solvent was evaporated under reduced pressure, and diethyl ether was added to the obtained residue. The precipitated solid was collected by filtration to give 4-cyano-4-(2-fluorophenyl)piperidine hydrobromide (0.27 g, yield 15%). 1H-NMR(300MHz,DMSO-d6)delta(ppm): 2.22-2.32(2H,m), 2.50-2.54(2H,m), 3.11-3.23(2H,m), 3.52-3.57(2H,m), 7.32-7.41(2H,m), 7.50-7.55(2H,m), 8.65(1H,s), 8.76(1H,s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63.8% | With N-ethyl-N,N-diisopropylamine; at 105℃; for 18.0h; | To a stirred solution of <strong>[210488-54-3](R)-1-(benzo[d][1,3]dioxol-5-yl)ethan-1-amine</strong> (2 g, 12.1 mmol) in DIPEA (4.22 mL, 24.2 mmol), N,N-bis(2-chloroethyl)-p-toluene sulfonamide (3.9 g, 13.3 mmol) was added at rt and the resulting mixture was heated to 105 C for 18 h. Completion of the reaction was confirmed by TLC. Reaction mixture was diluted with water (30 mL) and extracted with EtOAc (2 x 50 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum. To the resulting crude solid hexane (50 mL) was added, and the resulting mixture was stirred for 10 min at rt. It was filtered and the solid was washed with Et2O (2 x 50 mL) and dried under vacuum to give the title compound. Yield: 63.8% (3 g, off white solid). 1H NMR (400 MHz, DMSO-d6): δ 7.59 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 6.81-6.77 (m, 2H), 6.69-6.6 (m, 1H), 5.97-5.95 (m, 2H), 3.35-3.31 (m, 1H), 2.81-2.80 (m, 4H), 2.42 (s, 3H), 2.36-2.32 (m, 4H), 1.18 (d, J= 6.8 Hz, 3H). LCMS: (Method A) 389.0 (M+H), Rt. 3.39 min, 98.9% (Max). HPLC: (Method A) Rt. 3.30 min, 99.53% (Max), Chiral HPLC: (Method A) Rt. 15.54 min, 97.58%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63.2% | With N-ethyl-N,N-diisopropylamine; at 105℃; | To a stirred solution of (S)-1-(benzo[d][1 ,3]dioxol-5-yl)ethan-1-amine (41 g, 248 mmol) in DIPEA (86.6 mL, 496 mmol), N,N-bis(2-chloroethyl)-p-toluene sulfonamide (80.74 g, 273 mmol) was added at rt and the resulting mixture was heated at 105 C overnight. The completion of the reaction was confirmed by TLC and the reaction mixture was diluted with water (1000 mL) and extracted with EtOAc (2 x 500 mL). The combined organic layer was washed with water (200 mL), brine solution (200 mL) and dried over Na2SO4. After evaporation of the solvent, the resulting crude solid was suspended in pet ether (350 mL) and stirred for 10 min at rt. The suspension was filtered and was washed with Et2O (2 x 200 mL) and dried under vacuum to give the title compound. Yield: 63.2% (61 g, Off white solid). 1 H NMR (400 MHz, DMSO-d6): δ 7.59 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 8.2 Hz, 2H), 6.81-6.77 (m, 1H), 6.69 (d, J = 7.4 Hz, 1H), 5.96 (s, 2H), 3.32 (q, J = 7.76 Hz, 1H), 2.81-2.80 (m, 4H), 2.42 (s, 3H), 2.36-2.32 (m, 4H), 1.18 (d, J= 6.4 Hz, 3H). LCMS: (Method A) 389.2 (M+H), Rt. 3.40 min, 98.09% (Max). HPLC: (Method A) Rt. 3.30 min, 98.69% (Max). Chiral HPLC: (Method D) Rt. 15.79 min, 100.00% |
63.2% | With N-ethyl-N,N-diisopropylamine; at 105℃; | To a stirred solution of <strong>[210488-52-1](S)-1-(benzo[d][1,3]dioxol-5-yl)ethan-1-amine</strong> (41 g, 248 mmol) in DIPEA (86.6 mL, 496 mmol), N,N-bis(2-chloroethyl)-p-toluene sulfonamide (80.74 g, 273 mmol) was added at rt and the resulting mixture was heated at 105 C overnight. The completion of the reaction was confirmed by TLC and the reaction mixture was diluted with water (1000 mL) and extracted with EtOAc (2 x 500 mL). The combinedorganic layer was washed with water (200 mL), brine solution (200 mL) and dried over Na2SO4. After evaporation of the solvent, the resulting crude solid was suspended in pet ether (350 mL) and stirred for 10 mm at rt. The suspension was filtered and was washed with Et20 (2 x 200 mL) and dried under vacuum to give the title compound. Yield: 63.2% (61 g, Off white solid). 1H NMR (400 MHz, DMSO-d6): 6 7.59 (d, J = 8.2Hz, 2H), 7.45 (d, J = 8.2 Hz, 2H), 6.81-6.77 (m, IH), 6.69 (d, J = 7.4 Hz, IH), 5.96 (s,2H), 3.32 (q, J = 7.76 Hz, IH), 2.81-2.80 (m, 4H), 2.42 (s, 3H), 2.36-2.32 (m, 4H), 1.18(d, J= 6.4 Hz, 3H). LCMS: (Method A) 389.2 (M+H), Rt. 3.40 mm, 98.09% (Max).HPLC: (Method A) Rt. 3.30 mm, 98.69% (Max). Chiral HPLC: (Method D) Rt. 15.79mm, 100.00% |
63.2% | With N-ethyl-N,N-diisopropylamine; at 105℃; | To a stirred solution of <strong>[210488-52-1](S)-1-(benzo[d][1,3]dioxol-5-yl)ethan-1-amine</strong> (41 g, 248 mmol) in DIPEA (86.6 mL, 496 mmol), N,N-bis(2-chloroethyl)-p-toluene sulfonamide (80.74 g, 273 mmol) was added at rt and the resulting mixture was heated at 105 C overnight. Thecompletion of the reaction was confirmed by TLC and the reaction mixture was diluted with water (1000 mL) and extracted with EtOAc (2 x 500 mL). The combined organic layer was washed with water (200 mL), brine solution (200 mL) and dried over Na2SO4. After evaporation of the solvent, the resulting crude solid was suspended in pet ether (350 mL) and stirred for 10 mm at rt. The suspension was filtered and was washed with Et20 (2 x200 mL) and dried under vacuum to give the title compound. Yield: 63.2% (61 g, Off whitesolid). 1H NMR (400 MHz, DMSO-d6): 6 7.59 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 8.2 Hz, 2H),6.81-6.77 (m, IH), 6.69 (d, J = 7.4 Hz, IH), 5.96 (5, 2H), 3.32 (q, J = 7.76 Hz, IH), 2.81-2.80 (m, 4H), 2.42 (5, 3H), 2.36-2.32 (m, 4H), 1.18 (d, J= 6.4 Hz, 3H). LCMS: (Method A)389.2 (M+H), Rt. 3.40 mm, 98.09% (Max). HPLC: (Method A) Rt. 3.30 mm, 98.69% (Max).Chiral H PLC: (Method D) Rt. 15.79 mm, 100.00% |
63.2% | With N-ethyl-N,N-diisopropylamine; at 105℃; | To a stirred solution of <strong>[210488-52-1](S)-1-(benzo[d][1,3]dioxol-5-yl)ethan-1-amine</strong> (41 g, 248 mmol) in DIPEA (86.6 mL, 496 mmol), N,N-bis(2-chloroethyl)-p-toluene sulfonamide (80.74 g, 273 mmol) was added at rt and the resulting mixture was heated at 105 C overnight. The completion of the reaction was confirmed by TLC and the reaction mixture was diluted with water (1000 mL) and extracted with EtOAc (2 x 500 mL). The combined organic layer was washed with water (200 mL), brine solution (200 mL) and dried over Na2SO4. After evaporation of the solvent, the resulting crude solid was suspended in pet ether (350 mL) and stirred for 10 min at rt. The suspension was filtered and was washed with Et2O (2 x 200 mL) and dried under vacuum to give the title compound. Yield: 63.2% (61 g, Off white solid). 1H NMR (400 MHz, DMSO-d6): δ 7.59 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 8.2 Hz, 2H), 6.81-6.77 (m, 1 H), 6.69 (d, J = 7.4 Hz, 1 H), 5.96 (s, 2H), 3.32 (q, J = 7.76 Hz, 1 H), 2.81- 2.80 (m, 4H), 2.42 (s, 3H), 2.36-2.32 (m, 4H), 1.18 (d, J= 6.4 Hz, 3H). LCMS: (Method A) 389.2 (M+H), Rt. 3.40 min, 98.09% (Max). HPLC: (Method A) Rt. 3.30 min, 98.69% (Max). Chiral HPLC: (Method D) Rt. 15.79 min, 100.00% |
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