Structure of 55690-60-3
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CAS No. : | 55690-60-3 |
Formula : | C8H7NOS2 |
M.W : | 197.28 |
SMILES Code : | COC1=CC2=C(SC(S)=N2)C=C1 |
MDL No. : | MFCD00185941 |
InChI Key : | JDPITNFDYXOKRM-UHFFFAOYSA-N |
Pubchem ID : | 2830679 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 53.36 |
TPSA ? Topological Polar Surface Area: Calculated from |
89.16 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.37 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.39 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.59 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.45 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.38 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.44 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.06 |
Solubility | 0.173 mg/ml ; 0.000875 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.9 |
Solubility | 0.0246 mg/ml ; 0.000125 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.21 |
Solubility | 0.121 mg/ml ; 0.000614 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) |
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) |
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 |
-5.81 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 |
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) |
2.03 |
* 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 |
---|---|---|
With sulfuryl dichloride; at 0 - 20℃; for 2h; | Sulfuryl chloride (10 mL) was added to 5-methoxy-2- mercaptobenzothiazole at 0 0C. After complete addition, the reaction mixture was allowed to warm to it. After 2 h, the reaction mixture was poured into ice water (100 mL). This was allowed to warm to rt and was extracted with EtOAc (3 x). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was used without further purification. LC-MS: RT = 9.08 min., [M+H]+ = 234.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With sulfuryl dichloride; In tetrahydrofuran; | Sulfuryl chloride (1.64 mL) was added to a solution of 5-methoxy-2- mercaptobenzothiazole in THF (20 mL). After stirring overnight, ice water was added. The reaction mixture was allowed to warm to rt and was diluted with EtOAc (100 mL). This was washed with water (50 mL) and brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was purified by column chromatography (0 to 3% EtOAc in hexanes gradient), yielding 0.407 g (20%) of the title compound as a white solid. LC-MS: RT = 9.05 min., [M+H]+ = 2O0.0. R/= 0.38 in 10% EtOAc/Hexanes. |
A mixture of 5-methoxy-1,3-benzothiazole-2-thiol (500 mg), thionyl chloride (2 mL) and DMF (1 drop) was stirred at 50 C. for 3 days. Saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the obtained mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (211 mg).1H NMR (300 MHz, DMSO-d6) δ 3.84 (3H, s), 7.15 (1H, dd, J=9.0, 2.5 Hz), 7.53 (1H, d, J=2.5 Hz), 7.97 (1H, d, J=9.0 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 0.5h;Inert atmosphere; | To a mixture of 5-methoxy-1,3-benzothiazole-2-thiol (3.80 g, 19.2 mmol, CAS 55690-60-3) in DMF (50.0 mL) was added K2CO3 (5.32 g, 38.5 mmol) and CH3I (4.10 g, 28.8 mmol) at 0 C. The mixture was stirred at 20 C for 0.5 hour. On completion, the mixture was poured into the water (120 mL) and the aqueous phase was extracted with ethyl acetate (2 x 50 mL). The combined organic phase was washed with brine (2 X 50 mL), dried with anhydrous Na2SO4, filtered and concentrated in vacuo to give the title compound (4.00 g, 98% yield) as brown oil.1H NMR (400MHz, CDCl3) δ 7.60 (d, J = 8.8 Hz, 1H), 7.40 (d, J = 2.4 Hz, 1H), 6.94 (dd, J = 2.4, 8.8 Hz, 1H), 3.87 (s, 3H), 2.78 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bromine; In chloroform; at 0℃; for 1.5h; | Step 1.Synthesis of 2-bromo-5-methoxybenzothiazole A solution of bromine (3.6 eq) in chloroform (0.75M) was added dropwise over a period of 1 hr to a stirred suspension of <strong>[55690-60-3]5-methoxy-2-mercaptobenzothiazole</strong> (1 eq) in chloroform at 0 C. The mixture was stirred for 30 min before it was added slowly to water and stirred for further 20 min.The mixture was filtered to remove a cream solid.The organic phase was dried and evaporated to leave a brown solid.The brown solid was dissolved in ether and filtered.The residue was washed with ether and the filtrate and washings were combined and evaporated, chromatographed (4:1 hexanes and ethyl acetate) to give the title compound as a pale yellow solid. MS: MH+=244 | |
With bromine; In dichloromethane; chloroform; at 0 - 20℃; | A solution of bromine (1.2g, 7.5mmol) was added drop wise over a period of 1h to a stirred suspension of <strong>[55690-60-3]5-methoxy-2-mercaptobenzothiazole</strong> (1g, 5mmol) (7) in chloroform at 0oC. The mixture was stirred for 0.5h before it was added slowly to water and stirred for another 0.5h. The mixture was filtered to remove a creamy solid. The organic phase was dried with sodium sulfate and evaporated to obtain a brown solid. The brown solid was dissolved in ether and filtered. The residue was washed with ether and the filtrate and washings were combined and concentrated and chromatographed using 4:1 hexanes and ethyl acetate as the eluting solvent to give the title compound as a pale yellow solid. m/z: 242/244 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With methanol; potassium hydroxide;Heating / reflux; | 4-{4-(5-Methoxy-1,3-benzothiazol-2-thiolyl)butoxy}-7H-furo[3,2-g][1]benzopyran-7-on 539 mg (2.733 mmol) of 2-mercapto-5-methoxy-1,3-benzothiazole and 161 mg (2.869 mmol) of potassium hydroxide were refluxed in 25 ml of methanol until a clear solution was obtained. The solution was concentrated to dryness under vacuum. To the solid potassium salt was added 20 ml of anhydrous acetonitrile, 500 mg (1.708 mmol) of 5-(4-chlorobutoxy)psoralen, 333 mg (2.221 mmol) of sodium iodide and the resulting mixture was refluxed for 69 hours. The progress of the reaction was monitored by thin layer chromatography. After 69 hours the reaction mixture was concentrated under reduced pressure. The oily residue was cooled, diluted with water and acidified with concentrated hydrochloric acid to pH 1. The slurry was stirred for 15-20 min and extracted with 100 ml of dichloromethane. The dichloromethane layer was washed with 30 ml of 1% sodium hydroxide to separate the un-reacted 2-mercaptobenzothiazole followed by 30 ml of 2% hydrochloric acid, dried over anhydrous sodium sulfate and concentrated. The resulting oily residue was dissolved in methanol, treated with charcoal and re-crystallized from a petroleum ether-acetone (80:20) mixture. Yield: 599.8 mg (77.09%) Melting point: 134.8 C. 1H-NMR (500 MHz, CDCl3): δ [ppm]=8.09 (d, 1H, 3J=9.76 Hz, 3-H), 7.61 (d, 1H, 3J=8.9 Hz benzothiazole), 7.58 (d, 1H, 3J=2.24 Hz, 2'-H), 7.35 (d, 1H, 4J=2.2 Hz, benzothiazole), 7.14(s, 1H, 8-H), 6.97 (dd, 1H, 3J=8.9 Hz, 4J=2.1 Hz, benzothiazole), 6.95 (d, 1H, 3J=2.76 Hz, 3'-H), 6.18 (d, 1H, 3J=9.78 Hz, 4-H), 4.53 (t, 2H, 3J=5.78 Hz, 5-OC2CH2CH2CH2S-), 3.87 (s, 3H, O-C3), 3.48 (t, 2H, 3J=6.61 Hz, 5-OCH2CH2CH2C2S-), 2.11 (m, 4H, 5-OCH2C2C2CH2S-). MS (70 eV) m/z: 455 (6%, M+), 453 (44%), 328 (28%), 252 (100%, C12H14NOS2), 201 (6%), 196 (12%, C8H6NOS2), 174 (14%, [202-CO]+), 145 (8%), 89 (6%), 55 (28%, C4H7). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With triethanolamine; boron tribromide; In methanol; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; acetonitrile; | A. Preparation of 5-(2-chloroethoxy)-2-methylthio-benzothiazole To a 250 mL flask was added 2-mercapto-5-methoxybenzothiazole (5.1 g, 26 mmol), MeCN (63 mL), methyl p-toluenesulfonate (4.8 g, 26 mmol) and TEA (4.4 mL, 31 mmol). After stirring 16 h at ambient temperature, the solution was concentrated under reduced pressure. The crude material was diluted with EtOAc (200 mL), washed with water (2*75 mL), dried over Na2SO4, filtered, and concentrated. The resulting viscous oil was dissolved in DCM (40 mL), and transferred to an argon-purged 250 mL flask. The solution was cooled to -78 C. prior to the addition of a 1.0 M BBr3 solution in DCM (64 mL). The reaction suspension was allowed to warm to room temperature. After 16 h the reaction solution was cooled to -78 C. and quenched by addition of MeOH (100 mL). The resulting precipitates were isolated by vacuum filtration to yield 5-hydroxy-2-methylthio-benzothiazole (3.9 g, 76%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 143 Preparation of N-{3-[3-benzyl-5-(5-methoxy-3-methyl-3H-benzothiazol-2-ylidene)-4-oxothiazolidin-2-ylideneamino]-4-ethylaminophenyl}-2-dimethylaminoacetamide The title compound was prepared in a manner similar to Example 1 by replacing 2-(methylthio)benzothiazole with 2-mercapto-5-methoxybenzothiazole and by replacing aniline with 3'-amino-2-dimethylamino-4'-ethylaminoacetanilide. MS(ESI): 603 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.1% | 244 g of sodium polysulfide solution was mixed with 30 g of 1-chloro-4-methoxy-2-nitrobenzene, and then 20 mL of carbon disulfide was added with stiffing. The mixture was heated and refluxed for about 5 hrs and a yellow solid precipitated. The mixture was filtered and the filtrate was diluted with water to 1000 mL. An orange yellow solution was obtained. The solution was neutralized with hydrochloric acid (6M) to yield a light yellow solid. The solid was filtered, washed with water, and dried. 29.4 g of products was obtained with a yield of 93.1%. | |
(i) 2-Mercapto-5-methoxybenzthiazole yellow solid mp 198-200 C. (from 4-methoxy-2-nitrochlorobenzene) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In sodium hydroxide; water; acetone; | Step B 5-Methoxy-2-benzothiazolesulfonamide To a stirred solution of conc. aqueous ammonia cooled to 0 C. was added simultaneously a solution of 5-methoxy-2-benzothiazolethiol (3.8 g, 0.019 mole) dissolved in sodium hydroxide (800 mg in 20 ml H2 O) and a solution of aqueous sodium hydrochloride (5.25%, 20 ml) over a 1/2 hour period. The white sulfenamine which separated was filtered, washed with ice-H2 O and transferred to a round bottom flask with acetone (50 ml.) and water (90 ml). The stirred suspension was treated over a 1 hour period with 5% aqueous KMnO4 (88 ml). The resulting solution was filtered and acidified with HCl to give 3.7 g of 5-methoxy-2-benzothiazolesulonamide which melts at 186 C. after recrystallization from ethylene chloride. Analysis for C8 H8 N2 O3 S2: Calculated: C, 39.33; H, 3.30; N, 11.47, Found: C, 39.43; H, 3.36; N, 11.40. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With carbon disulfide; sodium hydroxide; In ethanol; | Step A 5-Methoxy-2-benzothiazolethiol A mixture of 2-amino-4-methoxybenzenethiol (7.0 g, 0.045 mole), sodium hydroxide (4.4 g, 0.11 mole) and carbon disulfide (8.06 g, 0.11 mole) in 90% aqueous ethanol (100 ml.) was heated at reflux for 2 hours, filtered, diluted with ice-water and acidified with hydrochloric acid to give 7.0 g of 5-methoxy-2-benzothiazolethiol which melts at 192-4 C. after recrystallization from benzene. Analysis for C8 H7 NOS2: Calculated: C, 48.71; H, 3.58; N, 7.10, Found: C, 49.13; H, 3.68; N, 7.31. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide; at 20℃; for 0.166667h; | Method 5 For weakly nucleophilic thiols more forcing conditions were required effect PyBOP mediated conversion of the 1-aryl pyrazine-2,3(1H,4H)-dione to a 3-thio substituted-1-arylpyrazin-2-ones. Accordingly, a DMF solution (0.4 mL) containing the 1-aryl pyrazine-2,3(1H,4H)-dione prepared in Part B (92 mg, 0.30 mmol), PyBOP (0.27 g, 0.53 mmol) and diisopropylethylamine (0.16 mL, 0.9 mmol) was stirred for 3 h before addition of a DMF solution prepared by stirring <strong>[55690-60-3]5-methoxybenzo[d]thiazole-2-thiol</strong> (296 mg, 1.502 mmol) with NaH (60.1 mg, 1.502 mmol, rinsed with hexane 2*) in DMF (0.2 mL) at ambient temperature for 10 min. After stirring at ambient temperature for 7 days, the reaction mixture was diluted with EtOAc and washed sequentially with water (2*) and brine prior to drying over MgSO4. After evaporation of the solvent, CH2Cl2 (10 mL) was added to the 0.30 g of crude product. Filtration to remove any residual solids followed by evaporation of the filtrate afforded 0.10 g crude product. Final purification required flash chromatography on 12 g silica gel using gradient elution (0 to 100% EtOAc/CH2Cl2) followed by preparatory HPLC (YMC S5 ODS 20*100 mm, 20 mL/min, 30 to 100% B in A over 10 min, Solvent A=10% MeOH/H2O-0.1% TFA, Solvent B=90% MeOH/H2O-0.1% TFA) to afford pure desired product (6.3 mg, 4% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80.5% | To 350 mL of an aqueous solution having 8.0 g of sodium hydroxide, 31.8 g of Intermediate (II) was added and stirred for 20 min. Subsequently, 70 mL of N, N-dimethylformamide (DMF) solution having 54 g of Intermediate (III) was added. The mixture was stirred at room temperature for 6 hrs and water added until the total volume was 1000 mL. The solution was extracted with dichloromethane, dried over anhydrous sodium sulfate, and the product purified by chromatography over silica gel eluted with ethyl acetate/hexane, 52.1 g of a yellow solid was obtained with a total yield was 80.5%. m.p. 85-87 C. 1H NMR (400 MHz, CDCl3) δ: 3.72 (s, 3H, COOCH3), 3.82 (s, 3H, CH-OCH3), 3.84 (s, 3H, OCH3), 4.52 (s, 1H, CH2), 6.94 (dd, J=2.4 Hz, J=8.8 Hz, 1H, ArH), 7.16 (t, J=4.6 Hz, 1H, ArH), 7.29-7.31 (m, 2H, ArH), 7.40 (d, J=2.8 Hz, 1H, ArH), 7.54-7.61 (m, 3H, CH-OCH3, ArH). EI MS: m/z (%) 401 (M+, 4), 369(19), 205 (11), 167 (24), 144 (100), 101 (37). Anal. Calcd for C20H19NO4S2: C, 59.83; H, 4.77; N, 3.49. Found: C, 59.89; H, 5.01; N, 3.27. | |
80.5% | To 350 mL of an aqueous solution having 8.0 g of sodium hydroxide, 31.8 g of Intermediate (II) was added and stirred for 20 min. Subsequently, 70 mL of N, N-dimethylformamide (DMF) solution having 54 g of Intermediate (III) was added. The mixture was stirred at room temperature for 6 hrs and water added until the total volume was 1000 mL. The solution was extracted with dichloromethane, dried over anhydrous sodium sulfate, and the product purified by chromatography over silica gel eluted with ethyl acetate/hexane, 52.1 g of a yellow solid was obtained with a total yield was 80.5%. m.p. 85-87C. 1H NMR (400 MHz, CDCl3) δ: 3.72 (s, 3H, COOCH3), 3.82 (s,3H,=CH-OCH3), 3.84(s, 3H, OCH3), 4.52 (s, 1H, CH2), 6.94 (dd, J = 2.4 Hz, J = 8.8 Hz,1H, ArH),7.16 (t, J = 4.6 Hz, 1H, ArH), 7.29-7.31 (m, 2H, ArH), 7.40 (d, J = 2.8Hz, 1H, ArH), 7.54-7.61 (m,3H, =CH-OCH3, ArH). EI MS: m/z (%) 401 (M+, 4), 369(19), 205 (11), 167 (24), 144 (100), 101 (37). Anal. Calcd for C20H19NO4S2: C, 59.83; H, 4.77; N, 3.49; Found: C, 59.89; H, 5.01; N, 3.27. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 6h;Inert atmosphere; | General procerure: To a suspension of mercaptan substituent heterocyclic in DMF, one equivalent of N-(3-bromopropyl) phthalimide and K2CO3 (1 equivalent) were added. The reaction was stirred for 6 h at 90 C before cooled to room temperature. After evaporation of the DMF under vacuum, the residue was diluted with methylene chloride, washed with water and brine, and dried over MgSO4. After evaporation of the solution, the crude products were purified by column chromatography eluting with 2.5:1 petroleum ether/acetone to afford the desired products as yellow or white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With sodium sulfide; at 80℃; for 10h;Microwave irradiation; | A 200 mL round bottom flask was charged with 80 g of a 10 wt% sodium sulfide solution, 10 g of starting material A, and carbon disulfide 10g, microwave heated to 80 C. The reaction to the raw material A disappeared (about 10h), stop the reaction, cooling to room temperature, adding 30% HCl to the reaction solution to ρH- = 4, suction drying product 10.40 g, yield 99%, 98% purity. |
93.1% | 244 g of sodium polysulfide solution was mixed with 30 g of 1-chloro-4-methoxy-2-nitrobenzene, and then 20 mL of carbon disulfide was added with stirring. The mixture was heated and refluxed for about 5 hrs and a yellow solid precipitated. The mixture was filtered and the filtrate was diluted with water to 1000 mL. An orange yellow solution was obtained. The solution was neutralized with hydrochloric acid (6M) to yield a light yellow solid. The solid was filtered, washed with water, and dried. 29.4 g of products was obtained with a yield of 93.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | In acetonitrile; at 50℃; for 12h;ultrasound irradiation; | General procedure: To a mixture of thio-compound (0.5 mmol), isocyanide (0.5 mmol) was added 0.1 mL acetonitrile. The system was irradiated by ultrasound in an appropriate time at 50 C until the thio-compound was completely consumed (monitored by TLC). Then the solvent was evaporated under the reduced pressure. The residue was purified by flash column chromatography with ethyl acetate and petroleum ether as eluent to afford pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With 1-methyl-3-decylimidazolium hydrogen sulfate; In acetonitrile; at 20℃; for 48h;Green chemistry; | General procedure: Thiols (1.0 mmol), benzylic alcohols (1.2 mmol), ionic liquid (0.1 mmol), and CH3CN (2 ml) were added into a flask. Then the mixture was vigorously stirred at room temperature, until thiols were completely consumed as indicated by TLC analysis. After the completion of reaction, the solvent of the resulting mixture was removed with the aid of a rotary evaporator, the residue was directly purified by flash column chromatography with ethyl acetate and petroleum ether (1:6) as eluents to afford pure product. |
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