Structure of 70260-17-2
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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. : | 70260-17-2 |
Formula : | C5H5BrOS |
M.W : | 193.06 |
SMILES Code : | OCC1=C(Br)C=CS1 |
MDL No. : | MFCD06202660 |
InChI Key : | IXULCOYQSDIBFO-UHFFFAOYSA-N |
Pubchem ID : | 12479011 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 38.15 |
TPSA ? Topological Polar Surface Area: Calculated from |
48.47 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.84 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.44 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.85 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.29 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.07 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.9 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.34 |
Solubility | 0.881 mg/ml ; 0.00456 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.06 |
Solubility | 1.67 mg/ml ; 0.00864 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.35 |
Solubility | 0.86 mg/ml ; 0.00446 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 |
-6.46 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 |
1.0 |
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) |
2.25 |
* 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 |
---|---|---|
100% | Stage #1: With sodium tetrahydroborate In methanol at 0℃; for 2 h; Stage #2: With ammonium chloride In ethyl acetate |
To a solution of 3- bromothiophene-2-carbaldehyde (500 mg, 2.62 mmol) in methanol (10 mL) was added sodium borohydride (169 mg, 4.47 mmol) in small portions at 0 °C and the reaction was stirred for 2 firs. The solvent was evaporated and the residue partitioned between ethyl acetate (20 mL) and 10percent ammonium chloride solution (10 mL). The organic layer was washed with water (10 mL), dried over sodium sulfate and evaporated. The title compound (505 mg, 2.62 mmol, 100percent) was obtained as a yellow oil. |
100% | With sodium tetrahydroborate In methanol at 0℃; for 2 h; | [00473] To a solution of 3-bromothiophene-2-carbaldehyde (6) (500 mg, 2.62 mmol) in methanol (10 mL) was added sodium borohydride (169 mg, 4.47 mmol) in small portions at 0 °C and the reaction was stirred for 2 hrs. The solvent was evaporated and the residue partitioned between ethyl acetate (20 mL) and 10percent ammonium chloride solution (10 mL). The organic layer was washed with water (10 mL), dried over sodium sulfate and evaporated. The title compound (505 mg, 2.62 mmol, 100percent) was obtained as a yellow oil. |
92% | With sodium tetrahydroborate In ethanol at 0 - 20℃; for 24 h; Inert atmosphere | Stirring of 3-bromothiophene-2-carboxaldehyde (compound (2-1), 10 g, 52.3 mmol) / ethanol (EtOH, 200 mL) at 0 ° C under argon, and adding sodium borohydride (NaBH 4 , 3.4 g, 90.1 mmol) and stirred at room temperature for 24 hours. An aqueous solution of ammonium chloride was added to the oily solid obtained by concentration of the reaction mixture under reduced pressure, and the organic layer was extracted with ethyl acetate. After the extract was dried over magnesium sulfate and filtered, the filtrate was concentrated under reduced pressure to give a crude material. The crude product was purified by a silica gel column chromatography (ethyl acetate / hexane (volume ratio) = 2 / 8) to thereby obtain 3-bromothiophene-2-methanol (the compound (3-1), The yield was 9.3 g, and the yield was 92percent) |
92% | at 0 - 20℃; for 24 h; Inert atmosphere | A solution of 3-bromothiophene-2-carboxaldehyde (compound (2-1), 10 g, 52.3 mmol) / ethanol (EtOH, 200 mL) was stirred at 0 ° C under an argon atmosphere, and sodium borohydride (NaBH 4 , 3.4 g, 90.1 mmol) and stirred at room temperature for 24 hours. An aqueous solution of ammonium chloride was added to the obtained oily solid, and the organic layer was extracted with ethyl acetate. After the extract was dried over magnesium sulfate and filtered, the filtrate was concentrated under reduced pressure to give a crude material. The crude product was purified by silica gel column chromatography (ethyl acetate / hexane (volume ratio) = 2/8), whereby 3-bromothiophene-2-methanol (the compound (3) -1), yield 9.3 g, yield 92percent). |
92% | With sodium tetrahydroborate In ethanol at 0 - 20℃; for 24 h; Inert atmosphere | In an argon environment,A solution of 3-bromothiophene-2-carbaldehyde (compound (2-1), 10 g, 52.3 mmol) / ethanol (EtOH, 200 mL) was stirred at 0 ° C.Sodium borohydride (NaBH4, 3.4 g, 90.1 mmol) was added on one side.Stir at room temperature for 24 hours.The oily solid obtained by concentrating the reaction liquid under reduced pressure is added to an aqueous solution of ammonium chloride.The organic layer was extracted with ethyl acetate.Drying the extract with magnesium sulfate,After filtering,The filtrate was concentrated under reduced pressure to give a crude product.The crude product was purified by column chromatography (ethyl acetate/hexane (volume ratio) = 2/8).And the target compound 3-bromothiophene-2-methanol was obtained.(Compound (3-1), yield 9.3 g, yield 92percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydrogenchloride; sodium chloride In tetrahydrofuran; water | A/Preparation of 3-Bromo-2-hydroxymethyl-thiophene: 2-(3-Bromothienyl)carboxylic acid (7 g; 34 mmoles) is dissolved in 25 ml of anhydrous THF. A solution of aluminium hydride AlH3 in anhydrous THF (2 M; 42 ml; 84 mmoles) is added slowly at a temperature of 0° C. At the end of the addition, the reaction mixture is refluxed for 3 hours. After cooling to 0° C., water (200 ml) and hydrochloric acid (1N, 150 ml) are added. The mixture is decanted and the aqueous phase extracted with 3*150 ml of tert-butyl methyl ether. The organic phases are combined and then washed with 150 ml of a saturated solution of sodium chloride, dried over magnesium sulphate and filtered. The solvent is evaporated under reduced pressure. The desired product is obtained as a brown oil and is used as such in the next step. Yield: 95percent; Physical characteristics: * NMR1H: (CD3OD) 4.69 ppm (s; 2H); 6.95 ppm (d; 1H, J=5.2 Hz); 7.39 ppm (d; 1H, J=5.2 Hz). * NMR13C: (DMSO-d6) 57.80 ppm; 106.28 ppm; 126.11 ppm; 129.80 ppm; 141.15 ppm. * MS: (EI, 70 eV); 194/192 (M+*; 80percent); 177/175 (30percent); 113 (50percent); 98 (60percent); 85 (100percent). |
73% | With sodium hydroxide; borane In tetrahydrofuran; methanol; (2S)-N-methyl-1-phenylpropan-2-amine hydrate | b. 3-Bromo-2-thiophenemethanol A stirred, ice-water chilled solution of 90.0 g of 3-bromo-2-thiophenecarboxylic acid and 600 ml of sieve dried tetrahydrofuran was treated at 5° C. with 962 ml of borane in tetrahydrofuran (1.04M solution) over 2 hours (nitrogen atmosphere), with exclusion of moisture. The stirred solution and cooling bath were allowed to equilibrate to ambient temperature overnight. The stirred, chilled (10° C.) solution was treated dropwise with 150 ml methanol over 2 hours and then with 100 ml of 10percent sodium hydroxide. After concentration, the residue was diluted with water, adjusted to pH=8 with 10percent sodium hydroxide solution and extracted with ether (2*300 ml). The combined dried (over anhydrous sodium sulfate) ethereal phase was concentrated. Distillation gave 61 g (73percent) of product, b.p. 79°-82° C. (0.38 mm). Analysis: Calculated for C5 H5 BrOS: 31.11percentC; 2.61percentH. Found: 31.30L percentC; 2.70percentH. |
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