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Structure of Methanesulfonic anhydride
CAS No.: 7143-01-3
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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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Search for reports by entering the product batch number.
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CAS No. : | 7143-01-3 |
Formula : | C2H6O5S2 |
M.W : | 174.20 |
SMILES Code : | CS(=O)(OS(C)(=O)=O)=O |
MDL No. : | MFCD00007556 |
InChI Key : | IZDROVVXIHRYMH-UHFFFAOYSA-N |
Pubchem ID : | 81560 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P260-P264-P280-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P363-P405-P501 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 30.74 |
TPSA ? Topological Polar Surface Area: Calculated from |
94.27 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.51 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.78 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.08 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.31 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.77 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.25 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.3 |
Solubility | 88.0 mg/ml ; 0.505 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.72 |
Solubility | 33.1 mg/ml ; 0.19 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.24 |
Solubility | 99.8 mg/ml ; 0.573 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 |
-7.92 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) |
3.09 |
* 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 |
---|---|---|
43% | at 105℃; for 3.5h;Inert atmosphere; | To a flame dried round bottom flask 0.5 g (3.6 mmol) of l-(2-hydroxyethyl)-lW- pyrrole-2,5-dione and 0.7 g (4.0 mmol) of methanesulfonic anhydride was added. The flask was evacuated and refilled with nitrogen. The flask was heated to 105C and stirred for 3.5 hr. The reaction was cooled to room temperature and dissolved in ethyl acetate (5 mL). The solution was taken up into a separatory funnel and washed four times with a saturated solution of sodium carbonate (40 mL). The aqueous layers were collected and washed with ethyl acetate (50 mL). The organic layers were combined and dried with MgS04 and concentrated in vacuo. The product was recrystallized from t-butyl methyl ether to yield 43 % (0.347 g, 1.58 mmol) of 2-(2,5-dioxo-2,5-dihydro-lH-pyrrol- l-yl)ethyl methanesulfonate.XH NMR (400 MHz, CD3CI) 6.78 (s, 2H), 4.41 (t, J = 5.23, 2H), 3.90 (t, J = 5.23, 2H), 3.04 (s, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With pyridine; In dichloromethane; at 0℃; for 1.5h; | To a solution of the product from Part B (3.10 g, 14.4 mmol) in CH2C12 (50 mL) were added pyridine (1.34 mL, 16. 58 mmol) and methane sulfonic anhydride (2.81 g, 16.13 mmol) sequentially at 0C. The reaction mixture was stirred for 1.5 h at 0C, then quenched with H2O, and extracted with EtOAc (3 x 50 mL). The organic phase was washed with H20, brine, and dried (Na2S04). The solvent was evaporated to afford (1S, 2S)-METHANESULFONIC acid 2-TERT-BUTOXYCARBONYLAMINO- cyclohexyl ester (4.0 g, 95%) as a white solid. MS M/Z 294.2 ([M+H]+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; dichloromethane; | b 3-[1-(3-Methanesulfonyloxymethylbenzyl)-indol-3-yl]-4-(1-methyl-indol-3-yl)-pyrrole-2,5-dione Methanesulfonic anhydride (0.35 g, 2.0 mmol) was added to a stirred solution of the product of step a) (0.234 g, 0.51 mmol) and <strong>[38222-83-2]2,6-di-tert-butyl-4-methylpyridine</strong> (0.42 g, 2.0 mmol) in dry CH2 Cl2 (15 mL) at room temperature. The reaction mixture was stirred for 16 h, and thereafter quenched by adding methanol (1.5 mL). The solvent was evaporated and the crude product chromatographed (ethyl acetate/heptane: 2/1) to yield 0.285 g of the sub-title product. 1 H-NMR (CDCl3):delta7.76 (1H, s); 7.66 (1H, s); 7.58 (1H, s); 7.38-7.24 (3H, m); 7.22-7.00 (6H, m); 6.82 (1H, d, J=8.05 Hz); 6.77 (1H, t, J=8.30 Hz); 6.68 (1H, t, J=8.05 Hz); 5.34 (2H, s); 5.18 (2H, s); 3.86 (3H, s); 2.83 (3H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | In dichloromethane; at 0 - 20℃; for 6h; | Preparation I; N-(5-methoxy-2-pyridinyl)methanesulfonamide; A solution of 10.7 g (86 mmol) of 5-methoxy-2-pyridinamine in 55 ml of dichioromethane is cooled to 0 C. and 72 ml (144 mmol) of a 2 M solution of methanesulfonic anhydride in dichloromethane are added gradually. The reaction mixture is stirred for 6 hours at room temperature and sodium bicarbonate solution is then added in a sufficient amount to bring the pH to about 9. The mixture obtained is concentrated under reduced pressure, the residue is taken up in 160 ml of ethanol at 50 C., the mixture obtained is dried and filtered and the filtrate is concentrated under reduced pressure. The residue is triturated in 50 ml of cold ethanol and the solid obtained is filtered off, rinsed with a little ethanol on the filter and then dried to give 8.7 g of the expected product in the form of a white powder (yield=50%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With triethylamine; In dichloromethane; at 20℃; for 16h; | Procedure S: Intermediate 24 (1-24) - 3-Nitrophenethyl methanesulfonate.; [00134] To a solution of 1.6 g (10 mmol, 1.0 eq.) of 2-(3-nitrophenyl) (1-23) in 20 mL of methylene chloride was added 2.8 mL (20 mmol, 2.0 eq.) of triethylamine. A solution of 1.7 g (10 mmol, 1.0 eq.) of methanesulfonic anhydride in 10 mL of methylene chloride was added and the mixture was stirred at room temperature for 16 h. The reaction mixture was washed with sat. brine and the organic layer was dried (Na2SC^). The solvent was removed in vacuo and the resulting residue was purified by flash chromatography to provide 2.2 g (9.0 mmol, 90%) of 3-nitrophenethyl methanesulfonate (1-24). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0℃; | Intermediate 2 is obtained from 1 according to the procedure in Example 1. To a mixture of 2 and diisopropylethyiamine in CH2CI2 at 0 0C is added Ms2O. The reaction mixture is stirred until the reaction is complete, as determined by thin layer chromatography (TLC). The reaction mixture is diluted with ethyl acetate and washed with cold sat. NaHCOs and brine. The organic layer is dried over Na2SO4, filtered and concentrated to provide mesylate 8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; at 80℃; | A mixture of Example 59A (1.50 g, 7.17 mmol), pyridine (1.74 mL, 21.51 mmol) and methanesulfonic anhydride (2.50 g, 14.34 mmol) in 60 mL 1 ,2-dichloroethane was stirred overnight at 80 C. The reaction mixture was concentrated and the residue was purified by flash chromatography (0-7% methanol/CH2Cl2) to afford the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With triethylamine; In dichloromethane; at 0 - 20℃; for 6h; | To a solution of (3S,4S)-1-benzylpyrrolidine-3,4-diol (3a) (6 g,31 mmol) and Et3N (12.8 mL, 93 mmol) in 200mL dry DCM wasadded dropwise a solution of methanesulfonic anhydride (12.9 g,74 mmol) in 100mL dry DCM at 0 C. The reaction was allowed towarm at R.T. for 6 h. The reaction mixture was washed with saturatedaqueous NaHCO3, 5% HCl and brine in sequence, dried overanhydrous Na2SO4, evaporated in vacuum, and purified by flashchromatography (petroleum ether:EtOAc 3:1) to afford 4a as lightyellow oil (8.5 g, 78%). 1H NMR (400 MHz, CDCl3) d 2.75 (dd,J 4.0 Hz, 11.2 Hz, 2H), 3.05 (s, 6H), 3.07-3.11 (m, 2H), 3.60-3.67(m, 2H), 5.12 (t, J 4.0 Hz, 2H), 7.26-7.34 (m, 5H); 13C NMR(100 MHz, CDCl3) d 38.3, 57.8, 59.1, 82.4, 127.5, 128.5, 128.7, 136.7;HRMS (ESI) m/z calcd for C13H19NO6S2 [MH] 350.0727, found350.0732. [a]D 20 24.6 (c 0.56, CHCl3). |