Structure of 5345-27-7
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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. : | 5345-27-7 |
Formula : | C8H8O4S |
M.W : | 200.21 |
SMILES Code : | O=C(O)C1=CC=CC(S(=O)(C)=O)=C1 |
MDL No. : | MFCD00216488 |
Boiling Point : | No data available |
InChI Key : | KUTBMATZUQWFSR-UHFFFAOYSA-N |
Pubchem ID : | 220380 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 46.5 |
TPSA ? Topological Polar Surface Area: Calculated from |
79.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.83 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.48 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.87 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.11 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.53 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.96 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.59 |
Solubility | 5.11 mg/ml ; 0.0255 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.73 |
Solubility | 3.77 mg/ml ; 0.0188 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.09 |
Solubility | 1.63 mg/ml ; 0.00817 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 |
-7.18 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 |
0.56 |
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) |
1.74 |
* 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 |
---|---|---|
90% | With borane-THF; In tetrahydrofuran; at 20℃; for 12h; | A solution of 3- (methylsulfonyl) benzoic acid (1.0 g, 5.0 mmol) in anhydrous THF (25 mL) was treated with BH3. THF (1 M solution, 7.5 mL) at room temperature. The reaction was stirred for 12 hours before it was quenched by slow addition of MeOH. The solvent was removed and the residue was purified by flash column chromatography (0-5 % MeOH in CH2CI2) to give the product (0.84 g, 90% yield NMR (300 MHz, CDCI3) 5 : 3.06 (s, 3 H), 4.81 (d, J = 6.0 Hz, 2 H), 7.54-7. 59 (m, 1 H), 7. 65-7.68 (m, 1 H), 7.85-7. 88 (m, 1 H), 7.96 (s, 1 H). |
63% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 15℃; for 14h; | To a solution of 34 (2.00 g , 9.99 mmol) in THF (10 mL) was added UAIH4(758 mg, 20.0 mmol) at 0 C. The mixture was stirred at 15 C for 14 h. The mixture was cooled to 0 C and quenched by saturated solution of potassium sodium tartrate (2mL), the precipitate formed was collected, filtered to remove the precipitate. The organic phase was concentrated in vacuo to give 35 (1 .40 g, 63%).1H N R (400 MHz, CDCI3) 7.97 (s, 1 H), 7.87 (d, J - 7.5 Hz, 1 H), 7.67 (d, J - 7.9 Hz, 1 H), 7.63 - 7.53 (m, 1 H), 4.82 (d , J = 5.7 Hz, 2H), 3.07 (s, 3H). |
51% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; | (13A) [3-(Methylsulfonyl)phenyl]methanol 3-(Methylsulfonyl)benzoic acid (540 mg, 2.70 mmol) was dissolved in tetrahydrofuran (40 mL), and the resulting solution was cooled to 0 C. Then, lithium aluminum hydride (102 mg, 2.70 mmol) was added thereto, and the temperature of the resulting mixture was raised to room temperature, and the mixture was stirred for 3 hours. Water was added to the reaction solution, and the organic matter was extracted with ethyl acetate. The organic layer was washed with water and a saturated sodium chloride solution, then dried over anhydrous magnesium sulfate and filtered. Then, the solvent was distilled off under reduced pressure, whereby a crude product was obtained. This crude product was purified by silica gel column chromatography (hexane:ethyl acetate=100:0 to 70:30 (v/v)), whereby the objective title compound was obtained as a colorless oily substance (257 mg, yield: 51%). 1H NMR (CDCl3, 400 MHz): delta1.26 (1H, brs), 3.06 (3H, s), 4.81 (2H, d, J=5.5 Hz), 7.57 (1H, t, J=7.8 Hz), 7.67 (1H, d, J=7.5 Hz), 7.86 (1H, d, J=7.5 Hz), 7.96 (1H, s) |
42% | With lithium aluminium tetrahydride; In tetrahydrofuran; diethyl ether; for 1h;Heating / reflux; | To an ice-cold solution of 3- (methylsulfonyl) benzoic acid (1.4 g, 7.1 mmol) in 2: 1 Et20/THF (60 mL) was added LIALH4 (8.5 mL of 1.0 M solution in THF, 8.5 mmol), and the reaction mixture was heated at reflux for 1 h. The reaction mixture was cooled to 0 C, and the reaction was quenched with water (15 mL) and 15% NaOH in water (35 mL). The reaction mixture was filtered, concentrated under reduced pressure, and the residue was dissolved in EtOAc. The organic solution was washed with water and then brine, dried (MGS04), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 1: 2 to 3: 1 EtOAc/hexanes) provided (3- methanesulfonyl) phenyl methanol as a clear oil (0.56 g, 42%) :H NMR (300 MHz, CDC13) 5 7.93 (s, 1H), 7.83 (d, J = 7 Hz, 1H), 7.64 (d, J = 7 Hz, 1H), 7.53 (t, J = 7 Hz, 1H), 4. 78 (d, J = 6 Hz, 2H), 3.05 (s, 3H), 2.61 (br s, 1H). |
With borane-THF; In tetrahydrofuran; at 0 - 20℃; for 0.166667h; | To an ice-cooled stirring solution of 1M BH3 in THF (25 ml_, 25 mmol) under inert atmosphere is added dropwise over a 10 minutes period a solution of 3- methanesulfonylbenzoic acid (2g, 10 mmol) in THF (20 mL). The reaction mixture is stirred at room temperature overnight then cooled down to 0C before adding water (2 mL). The solvent is removed under reduced pressure and the residue is partitioned between DCM and NaOH. The organic layer is isolated and dried over MgSO4 and filtered. The solvent is removed under reduced pressure to give (3-methanesulfonyl-phenyl)-methanol; [M-H]' 185. | |
With borane-THF; In tetrahydrofuran; at 0 - 20℃; | (3-Methanesulfonyl-phenyl)-methanol was prepared as follows: To 3- Methanesulfonyl-benzoic acid in THF at O0C was added dropwise a borane-THF complex and the reaction mixture stirred at room temperature overnight. Excess hydride was destroyed by slow addition of a water/THF mixture. The aqueous phase was saturated with potassium carbonate then extracted with ether. The organics were dried with MgSO4 and the solvent reduced in vacuo to yield (3-methanesulfonyl-phenyl)- methanol as a clear oil. | |
Borane solution (1M in THF) was added dropwise to a stirred mixture of 3-methylsulfonyl)benzoic acid (400 mg, 2.00 mmol) in anhydrous THF (2 ml) at 0 C. The resulting mixture was then allowed to warm to room temperature and stirred for 3 h. The reaction mixture quenched with water/1 M HCl (aq.), extracted with ethyl acetate (3 times), the combined organic extracts dried (sodium sulfate) and concentrated in vacuo to give crude (3-(methylsulphonyl)phenyl)methanol as an oil which was used in the next step without further purification. The alcohol was dissolved in dichloromethane (6 ml) and triethylamine (0.418 mL, 3.0 mmol). Methanesulfonylchloride (first batch (0.186 mL, 2.4 mmol) was then added, followed by a second batch (0.039 mL, 0.5 mmol) and the resulting mixture was stirred for 16 h. 1 N HCl solution (aq.) was then added and the reaction mixture was extracted with diethyl ether (3 times), the combined organic extracts were dried (sodium sulfate) and concentrated in vacuo. The residue was purified by column chromatography eluting using a gradient (petroleum ether 40/60/ethyl acetate 1:0 v/v 0:1) to afford 212 mg (52% over 2 steps) of the title compound as an oil. 1H NMR (CDCl3): 7.98 (1H, s), 7.91 (1H, d, J 7.8), 7.70 (1H, d, J 7.8), 7.59 (1H, t, J 7.8), 4.65 (2H, s), 3.08 (s, 3H). | ||
To a solution of Intermediate AX (l.Og, 4.99 mmol) in THF (20mL) at 0 C was added a solution of BH3DMS (0.94 mL, 9.98 mmol). After the addition was complete, the reaction mixture was stirred at 70 C for 1 hour. The reaction mixture was cooled, methanol (5.0 mL) was added, and the mixture was refluxed for 30 minutes. Solvent from the reaction mixture was removed via distillation, and the residue was diluted with ethyl acetate (30 mL), washed with water (2 x 15 mL) and brine (15 mL), dried over dried over anhydrous Na2S04, and the solvent was removed to afford the crude Intermediate AY (720mg, 77%) as an off white solid. This material was used in the next step without further purifications. NMR (CDC13): delta 7.95 (s, 1H), 7.85 (d, J = 7.88 Hz; 1H), 7.66 (d, J= 7.88 Hz, 1H), 7.56 (t, J= 7.65 Hz; 1H), 4.80 (s, 2H), 3.06 (s, 3H). Mass (M+H): 187.0. | ||
With borane-THF; boron trifluoride diethyl etherate; In tetrahydrofuran; at 0 - 20℃; | To a solution of 3-(methylsulfonyl)benzoic acid (1.2 g, 6:0 mmol) in THF (30 ml.) at 0 0C, is added equimolar amounts of borane (6.0 ml_ of a 1.0 M solution in THF) and boron trifluoride diethyl etherate (0.8 ml_, 6.0 mmol). The reaction is allowed to warm to ambient temperature overnight, and then quenched by pouring into a mixture of ice and solid NaHCO3. Following extraction with EtOAc, the organic layer is washed with brine and dried over Na2SO4. Removal of solvent affords the product as a colorless oil: MS (M+NH4)+ = 204. |
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