Structure of 492-97-7
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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. : | 492-97-7 |
Formula : | C8H6S2 |
M.W : | 166.26 |
SMILES Code : | C2=C(C1=CC=CS1)SC=C2 |
MDL No. : | MFCD00005414 |
InChI Key : | OHZAHWOAMVVGEL-UHFFFAOYSA-N |
Pubchem ID : | 68120 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 47.63 |
TPSA ? Topological Polar Surface Area: Calculated from |
56.48 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.34 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.75 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.48 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.37 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.98 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.38 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.91 |
Solubility | 0.0206 mg/ml ; 0.000124 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.63 |
Solubility | 0.00391 mg/ml ; 0.0000235 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.44 |
Solubility | 0.0598 mg/ml ; 0.00036 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) |
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) |
Yes |
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 |
-4.65 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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.39 |
* 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 |
---|---|---|
98% | With N-Bromosuccinimide; acetic acid; In chloroform; at 70℃; for 4h; | A mixture of 2,2'-bithiophene (5.40 g, 32.4 mmol) and NBS (11.57 g, 64.8 mmol, 2 equiv) in a solvent mixture CHCl3/acetic acid 100% (1:1 (v/v), 300 mL) was stirred at 70 C for 4 h. The reaction media was diluted with CH2Cl2 (50 mL) and a saturated aqueous solution of Na2CO3 (100 mL). The organic phase was isolated and the aqueous phase extracted with CH2Cl2 (3 x 50 mL). The organic phases were assembled, dried with MgSO4, filtered and evaporated to give a pale yellow solid that was then washed with acetone giving the pure product 1a (10.42 g, 98%). Recrystallization from THF afforded a highly pure product. 1H NMR (DMSO-d6, 600 MHz) δ (ppm): 7.23-7.22 (d, J = 3.9 Hz, 2H), 7.15-7.14 (d, J = 3.9 Hz, 2H). 13C NMR (DMSO-d6, 100 MHz) δ (ppm): 136.86, 131.60, 125.22, 110.84. MS(ESI+): m/z = 324.05. UV-visible (DMSO) λmax = 325 nm. IR(ATR): 3069 cm-1 (Ar-H)str; 1683 cm-1 (C=C conjugated)str; 1416 cm-1 (R1-C=C-R2 cis)str; 1293 cm-1 (C=C)bending. Elemental analysis: calculated: C 29.65; H 1.24; S 19.79; found: C 30.03; H 1.40; S 18.13. |
93% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; for 8h; | The compound 2, 2 '- bithiophene (1.66g, 10mmol) was dissolved in N,N-dimethylformamide (20 mL),N-Bromosuccinimide (0.31 g, 1.7 mmol) was dissolved in N, N-dimethylformamide (40 mL), and the latter was slowly added dropwise to the former. After the completion of the addition, the reaction was continued for 8 hours. After the completion of the reaction, a large amount of water was added. The petroleum ether was extracted, dried and filtered. The solvent was removed by rotary evaporation, and the crude product was recrystallized from ethanol as a white solid 19 (3.00 g, 93%). |
93% | With N-Bromosuccinimide; In chloroform; acetic acid; for 6h;Reflux; Inert atmosphere; | Under a dry argon atmosphere, 2,2′-bithiophene (2T) (3.00 g, 0.0180 mol) and N-bromosuccinimide (6.75 g, 0.0379 mol) were dissolved in chloroform/acetic acid (49 mL, 4:3, v/v). The resulting reaction mixture was refluxed for 6 h. Then, the reaction mixture was poured into the stirred mixture of chloroform and water. The organic layer was separated, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The crude product in the residue was purified by recrystallization from the mixed solvent of chloroform and methanol to afford Br2T as colorless crystals with the yield of 93% (5.46 g, 0.0168 mol). 1H NMR (CDCl3, 400 MHz, ppm): δ 6.96 (d, J=3.6 Hz, 2H, thienyl protons), 6.85 (d, J=4.1 Hz, 2H, thienyl protons). 13C NMR (CDCl3, 100 MHz, ppm): δ 137.8 (thienyl carbon), 130.7 (thienyl carbon), 124.2 (thienyl carbon), 111.6 (thienyl carbon). M.p.: 147 C. |
93% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; for 2h;Reflux; | 2,2′-bithiophene (11.7 g, 70.1 mmol) is dissolved in 500 mL of N,N-dimethylmethanamide, and N-bromo succinimide (31 g, 175.2 mmol) is added in a dropwise fashion to bromide it. Then, the resultant is refluxed for 2 hours, water (1 L) is added thereto, and the produced precipitate is filtered and recovered. The recovered powder is dissolved in chloroform (700 mL), washed with water, and then dried with magnesium sulfate followed by evaporating the resultant. The resultant is washed with n-hexane and dried to obtain Compound 1 (A yield of 93%). (0221) 1H-NMR (300 MHz, CDCl3): δ 6.96 (d, J=3.6 Hz, 1H), 6.85 (d, J=3.6 Hz, 1H) |
90% | With N-Bromosuccinimide; In N,N-dimethyl-formamide;Cooling with ice; | To a solution of 2, 2'-bithiophene (12 mmol, 2 g) in anhydrousDMF (30 ml), NBS (24 mmol, 4.28 g) was added dropwisely (coolingwith ice-water during addition of NBS solution) and stirred for 3 h.The reaction mixture was then poured into 100 mL of ice water andthe beige solid was separated by vacuum filtration [1]. The crudewas purified with column chromatography (silica gel100e200 mesh), using hexane as eluent to yield yellow solid asproduct (3.6 g, yield 90%). |
85% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; | N-Bromosuccinimide (NBS) (11.65 g, 65.450 mmol) was added in small portions to a solution of 2,2'-bithiophene 1 (5 g, 29.76 mmol) in DMF at 0 C. After being stirred over night at room temperature, the reaction mixture was poured into water (200 mL) and extracted with CH2Cl2. The organic layer was thoroughly washed with water, aqueous sodium bicarbonate, brine and again with water, and then dried over Na2SO4. After removal of solvent, it was purified by column chromatography on silica gel using petroleum ether as eluant to afford 5,5'-dibromo-2,2'-bithiophene (2) (8.20 g, 85%) as a white crystal solid. GC/MS: 324(M+). 1H NMR (400 MHz, CDCl3): δ(ppm) 6.97-6.96 (d, J = 4.0 Hz, 2H), 6.86-6.85 (d, J = 4.0 Hz, 2H). |
85.69% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 3h; | 2,2-Bithiophene (5.00 g, 30.1 mmol) was dissolved in N,N-dimethylformamide (50 mL). With stirring, N-bromosuccinimide (12.3 g, 69.2 mmol) was added at 0C and the reaction mixture was stirred at rt for 3 h. The mixture was poured into methanol (150 mL) and filtered to obtain a white solid product. Yield: 8.35 g (85.69%). 1H NMR (400 MHz, CDCl3): δ (ppm) 6.96 (d, J = 3.9 Hz, 2H), 6.85 (d, J = 3.9 Hz, 2H). |
57% | With water; sodium bisulfate hydrate; sodium bromide; In acetonitrile; for 96h;Irradiation; | In a 25mL reaction tube, add dithiophene (23.6mg, 0.2mmol), sodium bromide (61.6mg, 0.6mmol), sodium bisulfate hydrate (55.2mg, 0.4mmol), water (72mg, 4mmol) and Acetonitrile (2mL), stirred under the irradiation of three 2-watt LED lamps for 96 hours, after the reaction was completed, extracted, dried, filtered, concentrated, and separated by column chromatography to obtain a white solid 2v (37mg, 57%); |
51% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0℃; for 12h; | In dimethyl formamide, dissolved was 2- (thiophen-2- yl) thiophene (30 g, 0.18 mol) . Then, with the light shielded, N-bromosuccinimide (70.7 g, 0.4 mol) was diluted with dimethyl formamide, and the dilution was slowly added dropwise to the solution at 0 C After 12 hours, the reaction was quenched, extracted with methylene chloride, and dried over magnesium sulfate. The solvent was removed, and the residue was purified via chromatography to obtain the desired compound, 2-bromo-5- (5-bromothiophen-2 -yl) thiophene (Compound 16) (29.8 g, yield: 51%) . |