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Structure of 106-53-6
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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. : | 106-53-6 |
Formula : | C6H5BrS |
M.W : | 189.07 |
SMILES Code : | SC1=CC=C(Br)C=C1 |
MDL No. : | MFCD00004845 |
InChI Key : | FTBCOQFMQSTCQQ-UHFFFAOYSA-N |
Pubchem ID : | 66049 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H315-H319-H335-H301+H311+H331 |
Precautionary Statements: | P261-P264-P270-P271-P280-P302+P352-P301+P310-P304+P340-P305+P351+P338-P311-P330-P361+P364-P405-P403+P233-P501 |
Class: | 6.1 |
UN#: | 2811 |
Packing Group: | Ⅲ |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 41.39 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.8 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.11 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.25 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.74 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.31 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.86 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.85 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.61 |
Solubility | 0.0459 mg/ml ; 0.000243 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.74 |
Solubility | 0.0345 mg/ml ; 0.000183 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.36 |
Solubility | 0.0822 mg/ml ; 0.000435 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) |
No |
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 |
-5.15 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 |
1.0 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) |
1.22 |
* 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 triethylamine; In acetonitrile; for 17h;Reflux; | [00144] A mixture of 4-bromobenzenethiol (50 g, 0.26 mol), bromoethane (58 g, 0.53 mol) and triethylamine (78 g, 0.78 mol) in acetonitrile (1 L) was stirred at reflux for 17 h. The mixture was cooled to rt and filtered. The filtrate was concentrated under vacuum. The residue was purified by silica gel chromatography (eluting with petroleum ether) to give (4- bromophenyl)(ethyl)sulfane (55 g, 96%) as an oil. 1H NMR (CDC13, 400 MHz): δ 7.40-7.42 (dd, J = 6.4, 2.0 Hz, 2H), 7.18-7.20 (dd, J = 6.4, 2.0 Hz, 2H), 2.91-2.96 (q, J = 1.2 Hz, 2H), 1.30-1.33 (t, J = 7.2 Hz, 3H). |
96% | With triethylamine; In acetonitrile; for 17h;Reflux; | A mixture of 4-bromobenzenethiol (50 g, 0.26 mol), bromoethane (58 g, 0.53 mol) and triethylamine (78 g, 0.78 mol) in acetonitrile (1 L) was stirred at reflux for 17 h. The mixture was cooled to rt and filtered. The filtrate was concentrated under vacuum. The residue was purified by silica gel chromatography (eluting with petroleum ether) to give (4-bromophenyl)(ethyl)sulfane (55 g, 96%) as an oil. 1H NMR (CDCl3, 400 MHz): δ 7.40-7.42 (dd, J=6.4, 2.0 Hz, 2H), 7.18-7.20 (dd, J=6.4, 2.0 Hz, 2H), 2.91-2.96 (q, J=7.2 Hz, 2H), 1.30-1.33 (t, J=7.2 Hz, 3H). |
96% | With triethylamine; In acetonitrile; for 17h;Reflux; | A mixture of 4-bromobenzenethiol (50 g, 0.26 mol), bromoethane (58 g, 0.53 mol) and triethylamine (78 g, 0.78 mol) in acetonitrile (1 E) was stirred at reflux for 17 h. The mixture was cooled to it and filtered. The filtrate was concentrated under vacuum. The residue was purified by silica gel chromatography (eluting with petroleum ether) to give (4-bromophenyl)(ethyl)sulfane (55 g, 96%) as an oil. ‘H NMR (CDC13, 400 MHz): ö 7.40-7.42 (dd, J=6.4, 2.0 Hz,2H), 7.18-7.20 (dd, J=6.4, 2.0 Hz, 2H), 2.91-2.96 (q, J=7.2 Hz, 2H), 1.30-1.33 (t, J=7.2 Hz, 3H). |
96% | With triethylamine; In acetonitrile; for 17h;Reflux; | A mixture of 4-bromobenzenethiol (50 g, 0.26 mol), bromoethane (58 g, 0.53 mol) and triethylamine (78 g, 0.78 mol) in acetonitrile (1 L) was stirred at reflux for 17 h. The mixture was cooled to rt and filtered. The filtrate was concentrated under vacuum. The residue was purified by silica gel chromatography (eluting with petroleum ether) to give (4- bromophenyl)(ethyl)sulfane (55 g, 96%) as an oil. 1H NMR (CDC13, 400 IVIHz): 5 7.40-7.42 (dd, J 6.4, 2.0 Hz, 2H), 7.18-7.20 (dd, J 6.4, 2.0 Hz, 2H), 2.91-2.96 (q, J= 7.2 Hz, 2H), 1.30-1.33 (t, J 7.2 Hz, 3H). |
96% | With triethylamine; In acetonitrile; for 17h;Reflux; | [00199] Step 1: (4-bromophenyl)(ethyl)sulfane [0987] [00200] A mixture of 4-bromobenzenethiol (50 g, 0.26 mol), bromoethane (58 g, 0.53 mol) and triethylamine (78 g, 0.78 mol) in acetonitrile (1 L) was stirred at reflux for 17 h. The mixture was cooled to rt and filtered. The filtrate was concentrated under vacuum. The residue was purified by silica gel chromatography (eluting with petroleum ether) to give (4- bromophenyl)(ethyl)sulfane (55 g, 96%) as an oil. 1H NMR (CDC13, 400 MHz): δ 7.40-7.42 (dd, J = 6.4, 2.0 Hz, 2H), 7.18-7.20 (dd, J = 6.4, 2.0 Hz, 2H), 2.91-2.96 (q, J = 7.2 Hz, 2H), 1.30- 1.33 (t, 7 = 7.2 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12h; | 4-Bromobenzenethiol (0.3g, 1.59 mmol, 1.0 equiv) was dissolved in N, N-dimethylformamide (6 mL). Cs2CO3 (1.55 g, 4.76 mmol, 3.0 equiv), lodoethane (0.15 mL, 1.9 mmol, 1.2 equiv) were added and the reaction mixture was stirred at room temperature for 12 hours. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with brine, dried over sodium sulfate and concentrated to afford a crude residue. The crude residue was purified by silica gel column chromatography (0-5 % EtOAc/Hexane) to afford the desired product 5.18a (0.32 g, 93 % yield). 1H NMR (400 MHz, DMSO) 6 7.50 (d, J = 8.6 Hz, 2H), 7.26 (d, J = 8.6 Hz, 2H), 2.99 (q, J = 7.3 Hz, 2H), 1.23 (t, J = 7.3 Hz, 3H). |
88% | With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 20℃; for 18h; | To a solution of 4-bromobenzenethiol (6, 0.35 g, 1.85 mmol) in DMF (2 mL) was added sodium hydride (0.111 g, 60% dispersion in mineral oil, 2.77 mmol) followed by iodoethane (0.58 g, 3.7 mmol) and the mixture stirred for 18 h at r.t. The reaction mixture was diluted with water (40 mL) and extracted with EtOAc (2 x 50 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated. Purification of the resultant residue by column chromatography (eluant 5% EtOAc in hexanes) provided the title compound (0.356 g, 88% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) ppm 1.28 (t, J = 7.5 Hz, 3H), 2.89 (q, J = 7.5 Hz, 2H), 7.11-7.19 (m, 2H), 7.33-7.40 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 0 - 20℃; for 2h; | A solution of 4-bromobenzenethiol (670 mg, 3.55 mmol) and (L)-4-BROMO-2-TERT-BUTOXYCARBONYLAMINO-BUTYRIC acid methyl ester (1 g, 3.38 mmol) in DMF (15 mL) was cooled to 0 C and treated with CS2CO3 (1.2 g, 3.7 MMOL). Once the addition was complete, the reaction mixture was warmed to room temperature, stirred for 2 h, diluted with ethyl acetate (100 mL) and washed sucssevely with sat. aq NH4C1 and sat. aq NaCl. The resulting solution was dried over MGS04 concentrated and purified by flash column chromatography (10% ethyl acetate in heptane) to give 4- (4 -BROMOPHENYLSULFANYL)-2-TERT- Butoxycarbonylaminobutryic acid methyl ester (1.37g, 100 %) as SOLID. 1H NMR (CDC13), 6 7. 38 (d, J = 12 HZ, 2 H), 7.18 (d, J = 12 Hz, 2 H), 5.08 (d, J = 8 Hz, 1 H), 4.43 (m, 1 H), 3.73 (s, 3 H), 2.92 (m, 2 H), 2.21 (m, 2 H), 1.45 (s, 9 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With caesium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 2h; | Example 121; 2-tert-Butoxycarbonylamino-4- (4' -dibenzofuan-4-yl-biphenyl~4~ ylsulfanyl) -butryic acid; 1. 4- (4' -bromophenylsulfanyl) -2-tert-Butoxycarbonylaminobutryic acid methyl ester; A solution of 4-bromobenzenethiol (670 mg, 3.55 mmol) and (L) -4-bromo-2-tert-butoxycarbonylamino-butyric acid methyl ester (1 g, 3.38 mmol) in DMF (15 mL) was cooled to 0 0C and treated with CS2CO3 (1.2 g, 3.7 mmol) . Once the addition was complete, the reaction mixture was warmed to room temperature, stirred for 2 h, diluted with ethyl acetate (100 mL) and EPO <DP n="204"/>washed sucssevely with sat. aq NH4Cl and sat. aq NaCl. The resulting solution was dried over MgSO4 concentrated and purified by flash column chromatography (10% ethyl acetate in heptane) to give 4- (4' -bromophenylsulfanyl) -2-tert- Butoxycarbonylaminobutryic acid methyl ester (1.37g, 100 %) as solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 2,2,6,6-tetramethylheptane-3,5-dione; caesium carbonate; copper(l) chloride; In 1-methyl-pyrrolidin-2-one; at 130℃; for 2h;Inert atmosphere; Sealed tube; | N-Methyl-2-pyrrolidone (10 mL) was added to 4-bromothiophenol (0.500 g, 2.64 mmol) in a sealed tube and the mixture was purged with argon for 5 minutes. After this time, <strong>[3032-81-3]3,5-dichloroiodobenzene</strong> (0.72 g, 2.64 mmol), CuCl (0.131 g, 1.32 mmol), tetramethyl heptanedione (0.14 mL, 0.66 mmol) and cesium carbonate (1.70 g, 5.28 mmol) were added to the reaction mixture. The reaction mixture was stirred at 130° C. under argon for 2 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a celite bed. The filtrate was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the crude product. Silica gel chromatography (neat hexanes) provided impure 1-(4-bromo-phenylsulfanyl)-3,5-dichloro-benzene (0.7 g). MS calcd. for C12H8BrCl2S [(M+H)+] 334, obsd. 334. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 2,2,6,6-tetramethylheptane-3,5-dione; caesium carbonate; copper(l) chloride; In 1-methyl-pyrrolidin-2-one; at 130℃; for 2h;Sealed tube; Inert atmosphere; | N-Methyl-2-pyrrolidone (10 mL) was added to 4-bromothiophenol (0.500 g, 2.64 mmol) in a sealed tube and the mixture was purged with argon for 5 minutes. After this time, <strong>[175278-00-9]2-(trifluoromethoxy)iodobenzene</strong> (0.73 g, 2.53 mmol), CuCl (0.131 g, 1.32 mmol), tetramethyl heptanedione (0.14 mL, 0.66 mmol) and cesium carbonate (1.70 g, 5.28 mmol) were added to the reaction mixture. The reaction was stirred at 130 C. under argon for 2 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a celite bed. The filtrate was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the crude product. Silica gel chromatography (neat hexanes) provided impure 1-bromo-4-(2-(trifluoromethoxy)phenylsulfanyl)benzene (0.72 g) as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With di-tert-butyl peroxide; iodine; at 110℃; for 18h;Inert atmosphere; Sealed tube; Schlenk technique; Green chemistry; | General procedure: A 25 mL Schlenk tube equipped with a magnetic stirringbar was charged with I2 (12.7 mg, 0.05 mmol), substituted thiol1 (0.5 mmol) and alkyne 2 (0.75 mmol). The tube was evacuatedtwice and backfilled with nitrogen, and DTBP (2.5 mmol)was added into the tube under nitrogen atmosphere. The tubewas sealed with a balloon and the mixture was stirred undernitrogen atmosphere at 110 C for 18 h. Upon completion of thereaction, the resulting solution was cooled to r.t., and thesolvent was removed with the aid of a rotary evaporator. Theresidue was purified by column chromatography on silica gel(PE-EtOAc) to give 3. |