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CAS No. : | 100367-77-9 |
Formula : | C6H6BrNO2S |
M.W : | 236.09 |
SMILES Code : | C1=C(C(OCC)=O)N=C(S1)Br |
MDL No. : | MFCD03788564 |
InChI Key : | CNHISCQPKKGDPO-UHFFFAOYSA-N |
Pubchem ID : | 353965 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 45.9 |
TPSA ? Topological Polar Surface Area: Calculated from | 67.43 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 2.22 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 2.53 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 2.08 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 0.81 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 2.9 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 2.11 |
Log S (ESOL):? ESOL: Topological method implemented from | -3.04 |
Solubility | 0.217 mg/ml ; 0.00092 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -3.59 |
Solubility | 0.0603 mg/ml ; 0.000255 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -2.63 |
Solubility | 0.547 mg/ml ; 0.00232 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) | 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 | -5.94 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 | 0.55 |
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) | 2.86 |
* 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 |
---|---|---|
95% | With sodium tetrahydroborate; water; lithium chloride In tetrahydrofuran for 2 h; | Preparation of (2-bromothiazol-4-yl)methanol (5) To a solution of ester 4 (10.0 g, 42.4 mmol, 1 equiv) in THF (200 mL) was added NaBH4 (4.81 g, 127 mmol, 3 equiv), LiCl (5.4 g, 130 mmol, 3 equiv) and H2O (40 mL). The resulting biphasic mixture was vigorously stirred for 2 h, after which TLC (20percent EtOAc:hexanes) showed complete consumption of starting material. The reaction was quenched with saturated aqueous NH4Cl (200 mL), diluted with EtOAc (200 mL), and the layers were separated. The aqueous layer was extracted with EtOAc (100 mL), and the organic layers were combined, dried (Na2SO4), filtered, and concentrated under reduced pressure to give the title compound as a yellow semi-solid (7.82 g, 95percent). Rf= 0.2 (SiO2, 20percent EtOAcrhexanes); 1H and 13C NMR of the product matched those previously reported (Wipf and Wang 2007). |
91% | at 20 - 70℃; for 8 h; | 2-Bromothiazol-4-Carboxylic acid ethyl ester (11.8g, 50.0mmol)Was dissolved in absolute ethanol (100 mL)Sodium borohydride (3.8 g, 100 mmol) was added, stirred at room temperature for 4 hours, and then heated to 70 ° C for 4 hours.The solvent was evaporated under reduced pressure and the crude product was purified by column chromatography (ethyl acetate / petroleum ether (v / v) = 1/5) to give a pale yellow oil (8.85 g, 91percent). |
87% | With sodium tetrahydroborate In ethanol at 0 - 70℃; for 7.5 h; | At 0 , 2-bromo-thiazole-4-carboxylate (13.30g, 56.33mmol)In ethanol (150 mL) was added portionwiseSodium borohydride (4.263 g, 112.7 mmol),Stirring was continued at 0 0.5 hours.The mixture was stirred at room temperature for 3 hours,And heated to 70 ° C for 4 hours.The solvent was distilled off under reduced pressure,Slowly add water (100 mL)Extracted with ethyl acetate (100 mL x 3).Combine organic phase,Washed with saturated brine (50 mL)Dried over anhydrous sodium sulfate.Filtration, evaporation of the solvent under reduced pressure,The crude product was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 5/1)To give a colorless oil (9.5 g, 87percent). |
87% | With sodium tetrahydroborate In ethanol at 0 - 20℃; for 3 h; | Into a 500-mL round-bottom flask, was placed ethyl 2-bromothiazole-4-carboxylate (14 g, 59.30 mmol) and EtOH (200 mL). This was followed by the addition of NaBH4 (2.3 g, 60.53 mmol) in portions at 0oC. The resulting solution was stirred for 3 h at RT and then was quenched by the addition of 100 mL of water. The resulting solution was extracted with 2x200 mL of DCM and the organic layers combined and dried over anhydrous Na2SO4, then concentrated under vacuum. This resulted in 10 g (87percent) of the title compound as colorless oil. MS-ESI: 195.9, 193.9 (M+1). |
87% | at 0 - 20℃; for 3 h; | Into a 500-mL round-bottom flask was placed a solution of ethyl 2-bromothiazole-4-carboxylate(14 g, 59.3 mmol), EtOH (200 mL). This was followed by the addition of NaBH4(2.3 g, 60.5 mmol) in portions at 0°C. The resulting solution was stirred for 3 h at RT and then was quenched by the addition of 100 mL of water. The resulting solution was extracted with 2x200 mL of DCM.The organic layers were combined, dried over anhydrous Na2S04 and then concentrated under vacuum. This resulted in 10.0 g (87percent) of the title compound as colorless oil. MS-ESI: 195.9, 193.9(M+l). |
81% | at 20℃; for 3 h; Cooling | Into a 100-mL round-bottom flask was placed a solution of ethyl 2-bromo-1,3-thiazole-4- carboxylate (3 g, 12.71 mmol) in EtOH (30 mL). NaBH4 (1.0 g, 25.41 mmol) was added in portions with an ice/water bath. The resulting solution was stirred for 3 hr at room temperature. The reaction was then quenched by the addition of 100 mL of water in an ice/water bath. The resulting solution was extracted with 3x100 ml of ethyl acetate, and the combined organic layers were concentrated. This resulted in 2 g (81percent) of the title compound as yellow oil. MS-ESI: 196.2, 194.2 (M+1). |
68% | With sodium tetrahydroborate; lithium chloride In tetrahydrofuran; water at 0 - 20℃; for 16 h; | NaBH4 (2.49 g, 0.066 mol, 3 equiv), LiCl (2.79 g, 0.066 mol, 3 equiv) and H20 (30 mL) were added to a stirred solution ethyl 2-bromothiazole-4-carboxylate (1) (5.0 g, 0.022 mol, 1 equiv) in THF (50 mL) at 0 °C. The reaction mixture was allowed to warm to ambient temperature and stirred for 16 h. The reaction mixture was quenched with 1.5 M hydrochloric acid and the resulting mixture was extracted with ethyl acetate (2X150 mL). The combined organic layers were washed with water (150 mL), brine (150 mL), dried over Na2S04, filtered through celite bed and concentrated to provide compound 2 as a pale brown liquid (3.0 g, 68percent). LC-MS (ESI+): m/z 195.9 (M+H)+ 1H-NMR (300 MHz, DMSO-d6): δ 7.48 (s, 1H), 5.43 (t, J = 5.7 Hz, 1H), 4.52 (d, J = 5.7 Hz, 2H). |
67% | Stage #1: With lithium borohydride In tetrahydrofuran for 1 h; Cooling with an ice bath Stage #2: With methanol In tetrahydrofuran for 3.5 h; | Step 3 : (2-bromothiazol-4-yl)methanolA solution of ethyl 2-bromothiazole-4-carboxylate (7.821 g, 33.13 mmol) in THF (100 mL) was cooled in an ice-bath and treated portionwise with lithium borohydride (1.083 g, 49.70 mmol). After 1 hour MeOH (1.614 g, 2.040 mL, 50.36 mmol) was added over a period of half an hour. The reaction was allowed to stir for 3 hours and then the solvent was concentrated in vacuo and the resultant residue was dissolved in EtOAc, washed with HCl (2x), saturated sodium bicarbonate, followed by brine, dried (Na2SO4), concentrated and purified by column chromatography (EtOAc/Petroleum ether 1: 1) to give the required product as a colorless oil (4.3Og, 67percent Yield). 1H NMR (CDCl3, 400 MHz) δ 2.51 (IH, m), 4.75 (2H, m), 7.19 (IH, s); MS (ES+) 195.96 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 80℃; for 3h; | Step 1 - Synthesis of Intermediate Compound AATo a solution of 2-bromo-thiazole-4-carboxylic acid (2.0 mmol, 0.42 g), N1N- diisopropylethylamine (3.0 mmol, 0.52 ml_) and HATU (2.0 mmol, 0.76 g) in DMF (10 ml_) was added 4-(2-aminophenyl)-piperazine-1 -carboxylic acid te/t-butyl ester (2.0 mmol, 0.56 g). The reaction mixture was stirred at 80 0C for 3 h, and then concentrated in vacuo. Column chromatography on silica gel using Hexane/EtOAc (4.5/1) provided Compound A as a yellow solid (0.67 g, 72%). 1H NMR (400 MHz, CDCI3) D 10.38 (s, 1 H), 8.49 (dd, J= 8.0, 1.2 Hz, 1 H), 8.14 (s, 1 H), 7.23-7.10 (m, 3 H), 3.72 (br s, 4H), 2.89-2.87 (m, 4H), 1.50 (s, 9H). HPLC-MS RT= 2.39 minutes, mass calculated for formula Ci9H2SBrN4O3S 466.07, observed LCMS m/z 467.05 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 105℃; for 12h; | Example 39; Preparation of Intermediate Compound 39A; To a pressure tube charged with 2-bromo-4-carboethoxythiazole (2.5 g, 10.6 mmol) and a stir bar was added 6-methoxyisoindolin-1 -one (2.1 g, 12.7 mmol), K3PO4 (4.9 g, 23.3 mmol), Pd2(dba)3 (0.58 g, 0.64 mmol), Xant-Phos (0.62g, 1.1 mmol). Dioxane (20 mL) was added and N2 was bubbled thru the solution for 10 EPO <DP n="152"/>min before the vessel was capped. The mixture stirred at 105 C for 12h and was cooled to rt. The mixture was filtered thru a pad of Celite and was washed with CH2CI2/Me0H (20:1 ; 2 x 10 mL). The resulting filtrate was concentrated under reduced pressure and place under high vacuum. The crude product was purified using flash chromatography using a gradient from CH2Cb to 97:3 CH2CI2/acetone to provide 3.1 g (91% yield) of compound 39A as a brown solid. LC-MS [M+H] = 400.2; 98% purity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; In 1,4-dioxane; water; at 60℃; for 18.0h;Schlenk technique; Inert atmosphere; | General procedure: A 15-50 ml Schlenk-tube with magnetic stirring bar was evacuated and purged with Ar (repeated three times). The Schlenk-tube was subsequently charged with 5 mol-% Pd(OAc)2, 10 mol-% SPhos, 1.2 eq boronic acid, 1.0 eq aryl halide (if solid) and 5.0 mL 1 ,4-dioxane. At this point 1.0 eq aryl halide (if liquid) and 1.0 mL of a 3.4 M K3PO4 solution (degassed) was added via Eppendorf pipette in an Ar counterstream. The reaction mixture was degassed by evacuation and purging with Ar (repeated three times) and placed in an oil bath at 60 C. After stirring for 18-22 h (reaction control via TLC and GC/MS) the reaction mixture was cooled to RT, the phases separated and the organic phase filtered through a pad of Celite. The filter cake was washed with an appropriate amount of EtOAc, the volatiles were removed under reduced pressure and the crude residue was died in oil-pump vacuum. Pure product was obtained via flash column chromatography (S1O2, cyclohexane/EtOAc).Example 98: Ethyl 2-(4-(ethylthio)phenyl)thiazole-4-carboxylate (CLF-3-205) 4-(Ethylthio)benzeneboronic acid (92.5 mg, 0.508 mmol, 1.2 eq), ethyl 2-bromothiazole-4- carboxylate (100.0 mg, 0.424 mmol, 1.0 eq) and potassium phosphate (726.5 mg, 3.423 mmol, 8.1 eq) in 6.0 ml_ 1 ,4-dioxane/H20 5:1 (v/v) were reacted in presence of Pd(OAc)2 (4.8 mg, 0.021 mmol, 5 mol-%) and SPhos (17.4 mg, 0.042 mmol, 10 mol-%) for 18 h at 60 C according to general procedure C. The crude product was purified via flash column chromatography (16 g S1O2, cyclohexane/EtOAc 10:1 (v/v), column size 13 x 2 cm) to obtain the pure product as pale yellow solid.Yield: 69.9 mg (0.238 mmol, 56 %), pale yellow solid.C14H15NO2S2 [293.40 g/mol].Rf - 0.38 (cyclohexane/EtOAc = 5:1 (v/v); staining: KMnCb).1H NMR (300 MHz, CDC ): d = 8.12 (s, 1 H, Ar-H), 7.91 (d, J = 8.4 Hz, 2H, Ar-H), 7.33 (d, J = 8.3 Hz, 2H, Ar-H), 4.44 (q, J = 7.1 Hz, 2H, CH2), 3.01 (q, J = 7.3 Hz, 2H, CH2’), 1.52-1.26 (m, 6H, 2 x CH3).13C NMR (75 MHz, CDC ): d = 168.5, 161.6, 148.2, 141.0, 130.0, 127.9, 127.4, 126.8, 61.6, 26.9, 14.5, 14.2.HRMS (DI-EI): Calcd. for C14H15NO2S2: 293.0544; found: 293.0546. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride; In 1,2-dimethoxyethane; for 43h;Schlenk technique; Inert atmosphere; | General procedure: A predried 20 ml Schlenk tube with magnetic stirring bar was charged with 5 mol-% PdC Cdppf), 1.0 eq aryl halide, 1 .0-1.3 eq boronic acid and 2.1 eq cesium fluoride in anhydrous DME. The reaction mixture was degassed by evacuation and purging with Ar (repeated three times) and placed in an oil bath at 80 C. After stirring for 21 -96 h (reaction control via TLC and GC/MS) the reaction mixture was cooled to RT and filtered through a pad of Celite. The filter cake was washed with an appropriate amount of EtOAc, the volatiles were removed under reduced pressure and the crude residue was died in oil-pump vacuum. Pure product was obtained via flash column chromatography (S1O2, cycl o h exa ne/EtO Ac or toluene/EtOAc), unless otherwise stated. |
Tags: 100367-77-9 synthesis path| 100367-77-9 SDS| 100367-77-9 COA| 100367-77-9 purity| 100367-77-9 application| 100367-77-9 NMR| 100367-77-9 COA| 100367-77-9 structure
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P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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