Structure of 16694-18-1
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CAS No. : | 16694-18-1 |
Formula : | C5H3BrO2S |
M.W : | 207.05 |
SMILES Code : | O=C(C1=CC(Br)=CS1)O |
MDL No. : | MFCD03422294 |
InChI Key : | HJZFPRVFLBBAMU-UHFFFAOYSA-N |
Pubchem ID : | 610409 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 38.98 |
TPSA ? Topological Polar Surface Area: Calculated from |
65.54 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.48 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.15 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.21 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.35 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.62 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.96 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.82 |
Solubility | 0.311 mg/ml ; 0.0015 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.16 |
Solubility | 0.144 mg/ml ; 0.000694 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.9 |
Solubility | 2.61 mg/ml ; 0.0126 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 |
-6.04 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 |
0.56 |
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 |
---|---|---|
78% | Stage #1: With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 2 h; Stage #2: With ammonia In water; N,N-dimethyl-formamide at 0 - 20℃; for 5 h; |
A solution of 4 bromo-thiophene-2-carbo xylic acid (2.Og, 9.66mmol), l-ethyl-3-(3'- dimethylaminopropyl)carbodiimide hydrochloride (2.04g, 10.63mmol) and 1 -hydroxybenzotriazole hydrate (1.44g, 10.63mmol) in DMF (2OmL) is stirred at room temperature for 2 hours. The reaction mixture is then cooled to O0C and aq. NH3 (ImL, 17.3mmol) is added. The mixture is stirred at room temperature for an additional 5 hours, then water is added to the reaction mixture and the resultant precipitate is collected by filtration and washed with IM NaOH, H2O and petroleum ether. The title compound is isolated as a white solid (1.56g, 78percent). |
8 g | With N-hydroxybenzotriazole ammonium salt; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In acetonitrile | A) 4-bromothiophene-2-carboxamide [0504] To a solution of 4-bromothiophene-2-carboxylic acid (15 g), HOBt ammonium salt (16.5 g) and triethylamine (20.08 mL) in acetonitrile (250 mL) was added EDCI hydrochloride (16.87 g), and the mixture was stirred overnight. The reaction mixture was washed with saturated aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (8.0 g). 1H NMR (300 MHz, CDCl3) δ 5.87 (2H, brs), 7.43 (2H, q, J = 1.4 Hz) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sulfuric acid; at 25 - 50℃; for 12h; | To a solution of 4-bromo-2-thiophenecarboxylic acid (4g, 19 mmol) in MeOH (100 ml.) was added H2SO4 (5 ml.) dropwise at 25 0C. The solution was stirred for 12 h at 50 0C and was poured into ice-H2O and the pH was adjusted to ~1 1 with aqueous NaOH. The aqueous phase was extracted several times with DCM and the combined organic fractions were dried over Na2SO4, concentrated and used directly (4.27g, quant.): LCMS (ES) m/z 222 (M+H)+. |
100% | sulfuric acid; at 50℃; | Example 1; Preparation of Lambda/-{(1 S)-2-amino-1-[(3,4-difluorophenyl)methyl1ethyl}-4-(1 /-/-pyrazol-4-yl)-2- thiophenecarboxamide; a) methyl 4-bromo-2-thiophenecarboxylate; To a solution of 4-bromo-2-thiophenecarboxylic acid (7 g, 34 mmol) in MeOH (170 ml.) was added cone. H2SO4 (17 ml_). After heating to 50 0C for 12 h, the reaction solution was cooled to room temperature and diluted with CHCI3 (100 ml_). The CHCI3 solution was washed with cold aqueous NaHCO3, then 5N NaOH and dried over Na2SO4. Concentration under vacuum gave the title compound as a yellow oil (7.2 g, quant.): LCMS (ES) m/z 222 (M+H)+. |
95% | To a dry flask under N2 with a stirbar was added 6 g (29.1 mmol) of 4- bromothiophene-2-carboxylic acid (as prepared in the previous step) and dry methanol (100 mL). The solution was cooled in an ice-salt bath for 15 min and 2.55 mL (34.9 mmol) of thionyl chloride was added over 15 min, keeping the temperature <-5o C. The reaction mixture was stirred on the ice-salt bath for an additional 15 min, then for 1 h at rt, and finally refluxed for 8 h under N2. The resulting solution was cooled and concentrated to 6.7 g of pale amber oil. This oil was passed through 150 g of silica WITH ~600 mL CH2C12 (discarded the first 120 mL which contained minor impurities and no ester). The solvent was removed in vacuo to afford 6.11 g (95% yield) of the title compound as a colorless solid, which was used in the next step without further purification. |
91.4% | With thionyl chloride; for 6h;Reflux; | In 100ml single neck flask was added 4-bromo-2-thiophenecarboxylic acid 2.07g (10mmol), thionyl chloride 1.19g (10mmol) and absolute ethanol 25ml, refluxed, 6h After TLC showed the starting material is no longer remaining. The solvent was distilled off under reduced pressure, ice water was added, adjusting the pH with saturated sodium carbonate solution to 9 to 10, and extracted with ethyl acetate (40ml × 3), the combined organic phase was washed twice with saturated brine, dried over anhydrous MgSO 4, pale yellow oily liquid 2.02g, yield 91.4%. |
90% | With sulfuric acid; for 10h;Heating / reflux; | Example 1 : Methyl 4-{6-[4-(2-piperidin-l-ylethoxy)phenyllpyrazolo[l,5-alpyrimdin-3-vUthiophene- 2-carboxylate; Step 1 : methyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)thiophene-2-carboxylate; 4-Bromothiophene-2-carboxylic acid (0.418 g, 2 mmol) was dissolved in methanol (1 mL), and concentrated sulfuric acid (0.039 g, 0.4 mmol) was added. The mixture was refluxed for 1O h, poured into water, and subjected to 3-fold extraction with ethyl acetate. The organic layer was washed with K2CO3- solution, concentrated, dried over MgSO4, filtered and evaporated to give methyl 4-bromothiophene-2- carboxylate, weight 0.4 g (90% yield).A flask containing PdCl2(dppf) (0.32 g, 0.43 mmol), dppf (0.24 g, 0.43 mmol), KOAc (4.23 g, 0.043 mol), and pinacolediborone (5.5 g, 0.021 mol) was flushed with argon, then a solution of the ester from the foregoing step (3.2 g, 0.014 mol) in dioxane (60 mL) was added. The mixture was stirred at 850C under argon atmosphere for 40 h. Water (5-fold excess) was added, and the mixture was subjected to 3-fold extraction with ethyl acetate. The organic layer was washed with brine, concentrated, dried over MgSO4, filtered, and evaporated to give the crude methyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)thiophene- 2-carboxylate (5.1 g, purity 85% according to 1H NMR data). This crude boronate was used without further purification. |
With sulfuric acid;Heating / reflux; | Step 2 4-Bromo-thiophene-2-carboxylic acid (12.85g), CH30H (360 mL) and H2SO4 (95-98%, 6mL) were refluxed overnight. The solution was basified and evaporated to remove the organic solvent. The residue was extracted with EtOAc. The organic layer was washed with water and brine, then dried over Na2SO4, evaporated to give the product the solvent gave the product 4-Bromo-thiophene-2-carboxylic acid methyl ester (13 g). | |
With thionyl chloride; at -20℃; for 2.08333h;Reflux; | 4-bromo-2-thiophenecarboxylic acid (3.0 g) was dissolved in anhydrous methanol (30 mL) and cooled to -20 C.Then, thionyl chloride (5.1 g) was slowly added dropwise to the above mixture.After stirring for 5 minutes, the temperature was raised to reflux and the reaction was carried out for 2 h.The reaction was quenched with water and extracted with EtOAc.The extract is washed with saturated brine.After drying, it was concentrated to give a crude material (yellow oil, 3.24 g). | |
With thionyl chloride; for 6h;Reflux; | To a stirring solution of 4-bromo-2-thiophenecarboxylic acid (3g, 14.5mmol) in methanol (25mL) was added thionyl chloride (1.74g, 14.5mmol). Reaction mixture was heated to reflux and stirred for 6h. Upon completion, the residue was taken up in ice water (60mL). The pH was adjusted to 9-10 with saturated sodium carbonate solution. The aqueous phase was extracted with ethyl acetate (40mL×3). The combined organic phase was washed twice with saturated brine (20mL×2) and dried over anhydrous MgSO4. After filtering out MgSO4, the solvent of filtrate was removed in vacuo to afford crude product of title compound as a pale-yellow oil which was used for next step directly. Yield: 98%; 1H NMR (300MHz, CDCl3) delta: 7.69 (s, 1H), 7.45 (s, 1H), 3.90 (s, 3H). MS (m/z): [M+H]+ 221.0, 223.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With sulfuric acid; In methanol; at 65℃; for 17h; | A few drops of concentrated sulphuric acid are added to a solution of 5.0 g of the compound obtained during Stage 1 of Preparation 1 in 25 ml of methanol. The reaction medium is stirred at 65 C. for 17 hours and is then concentrated under reduced pressure. The oily residue obtained is dissolved in ethyl acetate (200 ml), washed with water (3×100 ml), dried over sodium sulphate and then concentrated under reduced pressure in order to produce 5.24 g of the desired product. Yield: 98% 1H NMR (CDCl3) delta (ppm): 3.90 (s, 3H), 7.45 (s, 1H), 7.70 (s, 1H) |
95% | With thionyl chloride; In methanol; dichloromethane; | b) Methyl 4-bromothiophene-2-carboxylate To a cooled (-20 C.) solution of 6.02 g (29.1 mmol) of 4-bromothiophene-2-carboxylic acid (as prepared in the previous step) in 100 mL of anhyd MeOH under nitrogen was added 2.55 mL (34.9 mmol) of thionyl chloride dropwise at a rate to keep the temperature below -5 C. (ca. 8-10 min). After stirring for 1 h at room temperature, the mixture was refluxed for 8 h, cooled, and concentrated in vacuo. The resulting 6.7 g of pale amber oil was passed through a 150 g pad of silica gel with ca. 600 mL of CH2Cl2 (discarding the first 120 mL which contained a minor impurity) to afford, after concentration in vacuo, the title compound as a colorless oil (6.11 g, 95%). 1H-NMR (300 MHz, CDCl3) delta7.69 (d, 1 H, J=1.5 Hz), 7.45 (d, 1 H, J=1.5 Hz), and 3.90 (s, 3 H). |
95% | With thionyl chloride; In methanol; dichloromethane; | b) Methyl 4-bromothiophene-2-carboxylate To a cooled (-20 C.) solution of 6.02 g (29.1 mmol) of 4-bromothiophene-2-carboxylic acid (as prepared in the previous step) in 100 mL of anhyd MeOH under nitrogen was added 2.55 mL (34.9 mmol) of thionyl chloride dropwise at a rate to keep the temperature below -5 C. (ca. 8-10 min). After stirring for 1 h at room temperature, the mixture was refluxed for 8 h, cooled, and concentrated in vacuo. The resulting 6.7 g of pale amber oil was passed through a 150 g pad of silica gel with ca. 600 mL of CH2Cl2 (discarding the first 120 mL which contained a minor impurity) to afford, after concentration in vacuo the title compound as a colorless oil (6.11 g, 95%). 1H-NMR (300 MHz, CDCl3) delta 7.69 (d, 1H, J=1.5 Hz), 7.45 (d, 1H, J=1.5 Hz), and 3.90 (s, 3H). |
95% | With thionyl chloride; In methanol; dichloromethane; | b 4-Bromothiophene-2-carboxylic acid Methyl Ester To a dry flask under N2 with a stirbar was added 6 g (29.1 mmol) of 4-bromothiophene-2-carboxylic acid (as prepared in the previous step) and dry methanol (100 mL). The solution was cooled in an ice-salt bath for 15 min and 2.55 mL (34.9 mmol) of thionyl chloride was added over 15 min, keeping the temperature <-5 C. The reaction mixture was stirred on the ice-salt bath for an additional 15 min, then for 1 h at rt, and finally refluxed for 8 h under N2. The resulting solution was cooled and concentrated to 6.7 g of pale amber oil. This oil was passed through 150 g of silica with ~600 mL CH2Cl2 (discarded the first 120 mL which contained minor impurities and no ester). The solvent was removed in vacuo to afford 6.11 g (95% yield) of the title compound as a colorless solid, which was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With methanol; sulfuric acid; at 50℃; for 18h; | To a solution of <strong>[62224-16-2]methyl 4-bromothiophene-2-carboxylate</strong> (2.0 g, 9.7 mmol) in dry MeOH (8 mL) was added H2SO4 (1-1.2 mL). The reaction mixture was heated to 50 C. for 18 h and was then concentrated under vacuum. The residue was dissolved in DCM and washed several times with saturated NaHCO3 solution. The organic fraction was dried (Na2SO4), concentrated under vacuum to provide 4-bromothiophene-2-carboxylic acid, which was used directly without further purification 1.73 g (81%). 1H NMR (400 MHz, DMSO-d): delta 7.69 (d, 1H, J=4.0 Hz), 7.26 (d, 1H, J=4.4 Hz), 3.82 (s, 3H). |
Tags: 16694-18-1 synthesis path| 16694-18-1 SDS| 16694-18-1 COA| 16694-18-1 purity| 16694-18-1 application| 16694-18-1 NMR| 16694-18-1 COA| 16694-18-1 structure
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P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
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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