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Structure of Isopropylsulphonyl chloride
CAS No.: 10147-37-2
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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. : | 10147-37-2 |
Formula : | C3H7ClO2S |
M.W : | 142.60 |
SMILES Code : | CC(S(=O)(Cl)=O)C |
MDL No. : | MFCD00007453 |
InChI Key : | DRINJBFRTLBHNF-UHFFFAOYSA-N |
Pubchem ID : | 82408 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P301+P330+P331-P302+P352-P304+P340-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3265 |
Packing Group: | Ⅱ |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 30.3 |
TPSA ? Topological Polar Surface Area: Calculated from |
42.52 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.33 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.19 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.04 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.38 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.42 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.41 |
Solubility | 5.58 mg/ml ; 0.0391 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.68 |
Solubility | 2.99 mg/ml ; 0.0209 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.22 |
Solubility | 8.61 mg/ml ; 0.0604 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 |
-6.32 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 |
2.0 |
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) |
2.08 |
* 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 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; at 0 - 20℃; for 1h; | Intermediate 1: N-(2.3-dihydro-1 H-inden-2-vl)-2-propanesulfonamideNHSCXjPr2-Aminoindan hydrochloride (5.16 g, 30 mmol, Sigma-Aldrich Company Ltd) was suspended in dry dichloromethane (100 ml), and cooled with stirring under argon to 0 C. To the suspension was added 1,8-diazabicyclo[5.4.0]undec-7-ene (3 eq., about 14ml, about 90 mmol) followed by the dropwise addition of isopropylsulfonyl chloride (6.8ml, 60 mmol). The cooling bath was removed and the mixture stirred at room temperature for 1 h. The reaction mixture was washed with 1 M hydrochloric acid (2 x 50 ml). The organic layer was separated, dried over sodium sulphate and evaporated in vacuo (ie under reduced pressure) to give a yellow oil (11.8 g). The crude product was purified by Chromatography on a 50g Isolute Flash silica-gel column eluting from 20-50% ethyl acetate in petroleum ether to give the title compound as a colourless solid (6.88 g, 96 %).1H-NMR (400MHz, CDCI3) 5 1.39 (6H, d, J = 7 Hz), 2.91 (2H, m), 3.18 (1H, m), 3.31 (2H, m), 4.31 (2H, m), 7.21 (4H, m). |
96% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; at 0 - 20℃; for 1h; | 2-Aminoindan hydrochloride (5.16 g, 30 mmol, Sigma-Aldrich Company Ltd) was suspended in dry dichloromethane (100 ml), and cooled with stirring under argon to 0 C. To the suspension was added 1,8-diazabicyclo[5.4.0]undec-7-ene (3 eq., about 14 ml, about 90 mmol) followed by the dropwise addition of isopropylsulfonyl chloride (6.8 ml, 60 mmol). The cooling bath was removed and the mixture stirred at room temperature for 1 h. The reaction mixture was washed with 1 M hydrochloric acid (2×50 ml). The organic layer was separated, dried over sodium sulphate and evaporated in vacuo (ie under reduced pressure) to give a yellow oil (11.8 g). The crude product was purified by chromatography on a 50 g Isolute Flash silica-gel column eluting from 20-50% ethyl acetate in petroleum ether to give the title compound as a colourless solid (6.88 g, 96%). 1H-NMR (400 MHz, CDCl3) delta 1.39 (6H, d, J=7 Hz), 2.91 (2H, m), 3.18 (1H, m), 3.31 (2H, m), 4.31 (2H, m), 7.21 (4H, m). |
96% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; at 0 - 20℃; for 1h; | 2-Aminoindan hydrochloride (5.16 g, 30 mmol, Sigma Aldrich Company Ltd.) was suspended in dry dichloromethane (100 ml), and cooled with stirring under argon to 0 C. To the suspension was added 1,8-diazabicyclo[5.4.0]undec-7-ene (14 g, 92 mmol) followed by the dropwise addition of isopropylsulfonyl chloride (8.56 g, 60 mmol). The cooling bath was removed and the mixture stirred at room temperature for 1 h. The reaction mixture was diluted with dichloromethane (50 ml) and washed with 1 M hydrochloric acid (2 x 50 ml). The organic layer was separated, dried over sodium sulphate and evaporated under reduced pressure to give a yellow oil (11.8 g). The crude product was purified by chromatography on a 50g Isolute Flash silica-gel column eluting from 20-50% ethyl acetate in 40-60 C petroleum ether to give the title compound as a pale yellow solid (6.88 g, 96 %); 1H-NMR (400MHz, CDCI3) 5 1.39 (6H, d, J = 7 Hz), 2.91 (2H, m), 3.18 (1H, m), 3.31 (2H, m), 4.31 (2H, m), 7.21 (4H, m). |
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; at 0 - 20℃; for 1h; | Description 1 : N-(2,3-dihydro-1 H-inden-2-yl)-2-propanesulfonamide2-Aminoindan hydrochloride (5.16 g, 30 mmol, Sigma-Aldrich Company Ltd) was suspended in dry dichloromethane (100 ml), and cooled with stirring under argon to 0 0C. To the suspension was added 1 ,8-diazabicyclo[5.4.0]undec-7-ene (3 eq., about 14ml, about 90 mmol) followed by the dropwise addition of isopropylsulfonyl chloride (6.8ml, 60 mmol). The cooling bath was removed and the mixture stirred at room temperature for 1 h. The reaction mixture was washed with 1 M hydrochloric acid (2 x 50 ml). The organic layer was separated, dried over sodium sulphate and evaporated in vacuo (ie under reduced pressure) to give a yellow oil (1 1.8 g). The crude product was purified by chromatography on a 5Og Isolute Flash silica-gel column eluting from 20-50% ethyl acetate in petroleum ether to give the title compound as a colourless solid (6.88 g, 96 %).1H-NMR (400MHz, CDCI3): 1.39 (6H, d, J = 7 Hz), 2.91 (2H, m), 3.18 (1 H, m), 3.31 (2H, m), 4.31 (2H, m), 7.21 (4H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With 1H-imidazole; In dichloromethane; at 20℃; for 1h; | A mixture of4-chloro-1 ,3-phenylenediamine (0.500 g, 3.51 mmol), isopropylsulfonyl chloride (0.39 mL, 3.49 mmol), imidazole (0.240 g, 3.53 mmol) and dichloromethane (2 mL) was stirred 1 h at room temperature, then the mixture chromatographed(silica gel, ethyl acetate/hexane) to give the title compound (0.269 g, 31percent) as an oil. 1 H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.38 (d, J=6.82 Hz, 6 H) 3.34 (septet, J=6.82 Hz1 1 H) 4.22 (s, 2 H) 6.54 (dd, J=8.59, 2.53 Hz, 1 H) 6.78 (d, J=2.53 Hz, 1 H) 7.14 (d, J=8.59 Hz, 1 H) 7.34 (s, 1 H) |
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