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CAS No. : | 2873-18-9 | MDL No. : | MFCD00014523 |
Formula : | C4H2BrClS | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ZFAJPWYXLYGUJU-UHFFFAOYSA-N |
M.W : | 197.48 | Pubchem ID : | 76133 |
Synonyms : |
|
Num. heavy atoms : | 7 |
Num. arom. heavy atoms : | 5 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 0.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 37.03 |
TPSA : | 28.24 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -4.96 cm/s |
Log Po/w (iLOGP) : | 2.17 |
Log Po/w (XLOGP3) : | 3.59 |
Log Po/w (WLOGP) : | 3.16 |
Log Po/w (MLOGP) : | 2.63 |
Log Po/w (SILICOS-IT) : | 3.98 |
Consensus Log Po/w : | 3.11 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 3.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.85 |
Solubility : | 0.0276 mg/ml ; 0.00014 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.87 |
Solubility : | 0.0267 mg/ml ; 0.000135 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.14 |
Solubility : | 0.143 mg/ml ; 0.000726 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 2.65 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H312-H315-H319-H332 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
96.7% | To a 2000 ml reaction flask was added 300 ml of tetrahydrofuran,Access to nitrogen protection,1.2g of iodine was added, dried over anhydrous magnesium turnings 6.8g,Controlled by the addition of 5 g of 2-bromo-5-chlorothiophene at a temperature of 22 C,After the success,Temperature control 28 ,A mixture of 800 ml of toluene and 45 g of 2-bromo-5-chlorothiophene was slowly added dropwise to the reaction flask,Drop finished,Cooling to 15 C stirring reaction for 50 minutes; (2) Then, 40 g of dry ice was added to the reaction solution,The reaction solution was cooled to -15 C or lower for 50 minutes,To the reaction solution was added 75 g of a 15% hydrochloric acid solution,Stirring reaction for 30 minutes;After completion of the reaction, the water bath temperature was controlled at 50 C to concentrate the reaction solution to the remaining small amount of the liquid under reduced pressure,Stop the distillation,To the residue was added 125 g of a 10% sodium hydroxide solution,Stir until the solid is dissolved,Static separation of organic layer,The aqueous layer was then washed with 100 ml of ethyl acetate,After separating the ethyl acetate layer,And 85 g of a 15% hydrochloric acid solution was added to the aqueous layer with stirring,The pH of the reaction solution is 2 to 3,After stirring for 15 minutes,The precipitated solid was filtered,The filter cake was washed with 30 ml of purified water,The resulting solid was dried to give 39.8 g of a white crystalline solid,The yield was 96.7% and the purity was 99.90%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;Pd(PPh3)4; In 1,2-dimethoxyethane; water; | EXAMPLE 29A 4-(2-chloro-3-thienyl)-benzoic acid Solid Pd(PPh3)4 (11.0 mg, 0.01 mmol) was treated with a room temperature solution of 2-bromo-5-chlorothiophene (143 mg, 0.72 mmol) in DME (4 mL), stirred for 5 minutes, treated with a solution of 4-(dihydroxyboryl)benzoic acid (100 mg, 0.60 mmol) in DME (2 mL), and stirred for 5 minutes. The mixture was treated with 2M Na2CO3 (1.5 mL, 3.0 mmol), heated to 75 C., stirred for 18 hours, cooled to room temperature, filtered, triturated with water (3 mL), and concentrated. The concentrate was treated with boiling water (4 mL), filtered through celite, cooled to room temperature, adjusted to pH<7 with HCl, and filtered to provide the desired product. MS (APCI(+)) m/e 239 (M+H)+. | |
With sodium carbonate;Pd(PPh3)4; In 1,2-dimethoxyethane; water; | Example 29A 4-(2-chloro-3-thienyl)-benzoic acid Solid Pd(PPh3)4 (11.0 mg, 0.01 mmol) was treated with a room temperature solution of 2-bromo-5-chlorothiophene (143 mg, 0.72 mmol) in DME (4 mL), stirred for 5 minutes, treated with a solution of 4-(dihydroxyboryl)benzoic acid (100 mg, 0.60 mmol) in DME (2 mL), and stirred for 5 minutes. The mixture was treated with 2M Na2CO3 (1.5 mL, 3.0 mmol), heated to 75 C., stirred for 18 hours, cooled to room temperature, filtered, triturated with water (3 mL), and concentrated. The concentrate was treated with boiling water (4 mL), filtered through celite, cooled to room temperature, adjusted to pH<7 with HCl, and filtered to provide the desired product. MS (APCI(+)) m/e 239 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28.2% | With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; N,N-dimethyl-formamide; for 3h;Heating / reflux; | (1) A 2N aqueous sodium carbonate solution (5.5 ml) was added to a mixed solution of compound 1 (0.5 g, 3.6 mmol), 2-bromo-5-chlorothiophene (0.6 ml, 5.5 mmol) and PdCl2(PPh3)2 (250 mg, 0.36 mmol) dissolved in DMF (17 ml). After subjecting to reflux under heating for 3 hours, the mixture was subjected to filtration with Celite. The filtrate was extracted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=20/1) to give compound 2 (215 mg, 28.2%) as powder. MS·APCI (m/z): 227/229 ([M+H+ MeOH-H2O]+) |
28.2% | With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In DMF (N,N-dimethyl-formamide); water; for 3h;Heating / reflux; | A 2N aqueous sodium carbonate solution (5.5 ml) was added to a mixed solution of compound 1 (0.5 g, 3.6 mmol), 2-bromo-5-chlorothiophene (0.6 ml, 5.5 mmol) and [PDCL2] (PPh3) [2] (250 mg, 0.36 mmol) dissolved in DMF (17 ml). After subjecting to reflux under heating for 3 hours, the mixture was subjected to filtration with Celite. The filtrate was extracted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=20/1) to give compound 2 (215 mg, 28. [2%)] as powder. MS-APCI (m/z): 227/229 ( [+)] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;[1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); In 1,2-dimethoxyethane; water; at 80℃; for 12h; | A mixture of Quinoline 4 [(L.] Oeq. ), 2-bromo-3-chloro-thiophene (2. [0EQ.),] Na2CO3 (3. 0eq. ; 2M in H20) and [PDCL2] [(DPPF)] 2 [(0.] [05EQ.)] in DME (0.2M) was stirred at [80C] for 12h. The mixture was cooled to rt and concentrated. Flash chromatography (Hex: EtOAc; 9: 1 to 1: 9 over 20 min) afforded the title compound as a yellow [SOLID.'H] NMR (400 MHz, acetone-d6) : [No. ] 8.93 (dd, 1H), 8.47 (dd, 1H), 8.3 (d, [1H),] 8.19 (d, [1H),] 7.97 (t, [1H),] 7.69-7. 64 (m, 2H), 7.60-7. 52 (m, 2H), 7. 35 (d, [1H),] 7.07 (d, 1H), 2.72 (s, 3H), 2.00 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate; sodium iodide;palladium diacetate; In N,N,N,N,N,N-hexamethylphosphoric triamide; at 90℃; for 16h; | A. 3-(5-Chloro-thiophen-2-yl)-propionaldehyde. To a mixture of Pd(OAc)2 (0.12 g, 0.53 mmol), NaHCO3 (0.52 g, 6.19 mmol) and NaI (0.28 g, 1.87 mmol) in 5 ML of HMPA is added 5-bromo-2-chloro-thiophene (1.00 g, 5.06 mmol) and allyl alcohol (1.03 ML, 15.2 mmol).The mixture is heated to 90 C. and stirred for 16 hours.The reaction mixture is cooled to room temperature, diluted with Et2O and washed with water.The organic layer is dried over MgSO4, filtered and concentrated in vacuo.The crude residue is purified by flash column chromatography eluding with a gradient of 10% Et2O/hexanes to 20% Et2O/hexanes to provide the product (0.18 g, 1.03 mmol) as an oil. 1H NMR (CDCl3, 300 MHz) delta9.81 (s, 1H), 6.71 (d, 1H), 6.58 (d, 1H), 3.07 (t, 2H), 2.81 (t, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With piperidine;copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); at 80℃; for 1h; | A. 3-(5-Chloro-thiophen-2-yl)-prop-2-yn-1-ol. nitrogen (g) is bubbled through a solution of 5-bromo-2-chloro-thiophene (1.00 g, 5.06 mmol) in 8 ML of piperidine.After 5 min, propargyl alcohol (0.32 ML, 5.56 mmol), tetrakis(triphenylphosphine) palladium(0) (0.06 g) and CuI (catalytic amount) are added to the solution.The mixture is heated at 80 C. for 1 h in a sealed glass vessel.At this time, the mixture is cooled and diluted with EtOAc/Et2O. The organic layer is washed 3N HCl, water, saturated NaHCO3 solution and saturated NaCl solution.The organic layer is dried, filtered and concentrated.The crude residue is purified via flash column chromatography eluding with a gradient of 10% EtOAc/hexanes to 20% EtOAc/hexanes to give the title compound (0.8 g, 0.46 mmol) as an oil. 1H NMR (DMSO-d6, 300 MHz) delta6.99 (d, 1H), 6.80 (d, 1H), 4.49 (s, 2H), 1.90 (bs, 1H). EI MS, [M]+=172, 174 (Cl pattern). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine;palladium diacetate; at 90℃; for 49h;Heating / reflux; | Compound 6 A mixture of 3.5 grams of 1-dimethylsulfamoyl-4-tributylstannylpyrazole, 2.4 ML of <strong>[2873-18-9]2-bromo-5-chloro-thiophene</strong>, 1.1 grams of triphenylphosphine, and 0.24 gram of palladium (II) acetate was heated at reflux for 4 hours and at 90 C. for 16 hours.Then, 1.5 ML of 2-bromo-5-chlorothiophene was added and the mixture was heated at reflux for 6 hours.One ML of 2-bromo-5-chlorothiophene was added and the mixture was heated at 90 C. for 16 hours and then heated at reflux for 7 hours.The mixture was permitted to cool and was then filtered.The filtrate was concentrated and partitioned between hexane and acetonitrile.The acetonitrile phase was concentrated and purified by chromatography on silica, eluding with methylene chloride to give crude 2-dimethylsulfamoyl-4-(5-bromo-2-thienyl)pyrazole.This material was dissolved in 10 ML of dioxane and 10 ML of 6 M hydrochloric acid and heated on a steam bath for 1 hour.The mixture was basified with 3 M sodium hydroxide and extracted into ethyl acetate.The organic solution was concentrated and purified by chromatography on silica.The residue was stirred in 10 ML of dimethyl sulfoxide with 5 grams of potassium carbonate and 2 ML of 2-bromofluoroethane for 16 hours.The mixture was partitioned between water and ethyl acetate and the organic phase was concentrated.The crude product was purified by chromatography on silica, eluding with 50% ethyl acetate methylene chloride to give 1-(2-fluoroethyl)-4-(5-chloro-2-thienyl)pyrazole. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
tris-(dibenzylideneacetone)dipalladium(0); trifuran-2-yl-phosphane; In 1,4-dioxane; at 100℃; for 15h; | The 3-benzyloxy-4-(5-chlorothiophen-2-yl)-1-(toluene-4-sulfonyl)-1H-pyrazole can be prepared in the following way: 589 mg of 2-bromo-5-chlorothiophene, 32.5 mg of tris(trifuryl)phosphine and 34.7 mg of tris(dibenzylideneacetone)dipalladium are added, with stirring and under an inert atmosphere, to a solution of 1.8 g of 3-benzyloxy-1-(toluene-4-sulfonyl)-4-tributylstannanyl-1H-pyrazole in 20 cm3 of dioxane. The reaction medium is heated at a temperature in the region of 100 C. for 15 hours. The mixture is then cooled to a temperature in the region of 20 C., and filtered over supercel. The filtrate is concentrated to dryness under reduced pressure (2 kPa), and taken up with cyclohexane; the insoluble material is filtered off over sintered glass, and the filtrate is concentrated to dryness under reduced pressure (2 kPa); the residue obtained is purified on an FC50SI-HP silica cartridge, eluding with a mixture of cyclohexane and ethyl acetate (90/10 by volume). 200 mg of 3-benzyloxy-4-(5-chlorothiophen-2-yl)-1-(toluene-4-sulfonyl)-1H-pyrazole are obtained in the form of a yellow powder. Mass spectrum (EI): m/z 444 (M+.), m/z 289 and m/z 91 (base peak). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In DMF (N,N-dimethyl-formamide); at 100℃; for 16h; | Example 187; 4- [3- (5-Chloro-thiophen-2-yl)-indole-l-sulfony]-N- (4-fluoro-benzvl)-benzamide; Combine N- (4-Fluoro-benzyl)-4- [3- (4, 4,5, 5-tetramethyl- [1, 3,2]-dioxaboralan-2- yl)-indole-l-sulfonyl]-benzamide (0.534 g, 1.0 mmol), <strong>[2873-18-9]2-bromo-5-chloro-thiophene</strong> (0.012 mL, l. lmmol), PdCl2 (dppf), CH2Cl2 (. 051g,. 069 mmol) and KOAc (0.294g, 3.0 mmol) in dry DMF (22.0 mL) under N2 heat and stir at 100 C for 16 h. Cool to ambient temperature and pour into a mixture of EtOAc-H20. Separate and extract the EtOAc several times with H20, wash with brine and dry (MgS04). Filter and evaporate to an oily residue. Purify the product by chromatography using a hexane-EtOAc gradient 0-100% EtOAc to give 0.209 g (40%) of a viscous oil. TOF MS (M-1) 523.0332. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene; | Reaction of the product of step 2 from example 65 (0.100 g, 0.218 mmol) with 2-bromo-5-chlorothiophene in toluene according to the general coupling procedure of Example 65 afforded, after HPLC purification, 0.016 g (18%) of Example 68 as a solid. MP 120 C.; TLC (elution with 5% methanol-methylene chloride) Rf =0.24; 1 H NMR (CDCl3, 300 MHz) delta 7.93 (d, J=8.5 Hz, 2H), 7.56 (d, J=8.5 Hz, 2H), 7.14-7.28 (m, 6H), 6.92 (d, J=3.7 Hz, 1H), 3.42 (dd, J=8.1, 16.9 Hz, 1H), 3.00-3.13 (m, 2H), 2.64 (brt, J=7.0 Hz, 2H), and 1.680-1.78 (m, 4H); FAB-LCIMS: 413 [M+H]+. STR121 Preparation of 4-Ethoxybenzeneboronic Acid A one-necked, 25-mL, round-bottomed flask equipped with a reflux condenser fitted with an argon inlet adapter was charged with magnesium powder (0.255 g, 10.5 mmol, -50 mesh), 7 mL THF, and 4-bromophenetol (1.41 g, 1.00 mL, 7.00 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(l) 9-(5-Chlorothien-2-yl)-9H-fluoren-9-ol from 2-bromo-5-chlorothiophene and 9-fluorenone; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With nitrogen; sodium carbonate;tetrakis(triphenylphosphine)palladium (0); | A 100 ml flask equipped with condenser, magnetic stirrer and nitrogen inlet was charged with 1.65 g (0.010 mol) of 2-bromo-5-chlorothiophene, 0.3 mmol of tetrakis(triphenylphosphine)-palladium(0) and 50 ml 1,2-dimethoxyethane. After stirring for 10 min, 2.95 g (0.011 mole) of 2,4-di-tert.butoxy-5-pyrimidineboronic acid was added immediately followed by 20 ml of 1M sodium carbonate solution. The reaction mixture was refluxed for 4 hours with vigorous stirring under nitrogen. After cooling to room temperature the traces of the catalyst were filtered off, the organic solvent was evaporated under reduced pressure and the residue was diluted with water and extracted with three portions of ether. The combined etheral phases were washed with water, saturated sodium chloride solution and dried over magnesium sulphate. The solvent was evaporated and the residue purified by flash-chromatography on silica gel giving 2.6 g (76%) of 2,4ditert.butoxy-5-(5'-chloro-2'-thienyl)pyrimidine mp 82.0-83.5 C. Anal. Found C 56.4, H 6.24, N 8.16, S 9.52. Calc. for C16 H21 ClN2 O2 S (340.9): C 56.37, H 6.21, N 8.22, S 9.41. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; In tetrahydrofuran; | Step A Synthesis of (5-chlorothien-2-yl)tributyl tin as an intermediate A stirred solution of 5.1 mL (0.046 mole) of 2-bromo-5-chlorothiophene in 200 mL of tetrahydrofuran was cooled to -85 C., and 19.7 mL (0.049 mole) of n-butyllithium (0.049 mole--2.5M in hexanes) was added dropwise during a 15 minute period. The reaction mixture temperature was maintained at -85 C. to -80 C. throughout the addition. Upon completion of addition, the reaction mixture temperature was maintained at about -80 C. for one hour. After this time, a solution of 12.5 mL (0.046 mole) of tributyltin chloride in 50 mL of tetrahydrofuran was added to the cold reaction mixture during a 10 minute period. Upon completion of addition, the reaction mixture was stirred at -80 C. for one hour, then it was allowed to warm gradually to ambient temperature. The reaction was quenched with an aqueous solution saturated with ammonium chloride, and then the reaction mixture was extracted with three 150 mL portions of diethyl ether. The combined extracts were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 18.4 grams of (5-chlorothien-2-yl)tributyl tin. The NMR spectrum was consistent with the proposed structure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
125 mg (56%) | tetrakis(triphenylphosphine)palladium (0); In tetrahydrofuran; | EXAMPLE 218 (+)-(4aR)-(10bR)-4-methyl-8-(5-chloro-2-thienyl)-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one STR236 A 15 mL round bottom flask was charged with (+)-(4aR)-(10bR)-4-methyl-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one-8-boronic acid (178 mg, 0.65 mmol), tetrakis(triphenylphosphine)palladium(0) (23 mg, 0.02 mmol), 2-bromo-5-chlorothiophene (128 mg, 0.65 mmol), 0.65 mL of 2M aqueous sodium carbonate and 2 mL of THF, fitted with a reflux condenser, and the stirred mixture was heated at 80, under nitrogen, for 24 h. The mixture was cooled, diluted with ethyl acetate (75 mL) and washed with brine (2*25 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (ethyl acetate eluent) to give 125 mg (56%) of the title compound as an oil. FDMS: m/e=345. alpha[D]589 =+74.03 (c=0.51, chloroform). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10 mg (22%) | In ethyl acetate; | EXAMPLE 189 6-(5-Chloro-2-thienyl)-1,2-dihydro-2,2,4-trimethylquinoline (Compound 289, structure 4 of Scheme II, where R1 =5-chloro-2-thienyl) This compound was prepared by General Method 2 (EXAMPLE 9) from Compound 9 (50 mg, 0.158 mmol) and 2-bromo-5-chlorothiophene (63 mg, 0.315 mmol). Purification by flash chromatography on silica gel (20 g) using 5% EtOAc:hexanes afforded 10 mg (22%) of Compound 289 as a yellow oil. Data for Compound 289: 1 H NMR (400 MHz, acetone-d6) 7.21 (d, J=2.1, 1H), 7.1 (dd, J=8.1, 2.0, 1H), 7.02 (d, J=3.7, 1H), 6.93 (d, J=3.7, 1H), 6.51 (d, 8.3, 1H), 5.42 (br s, 1H), 5.40 (s, 1H), 2.01 (s, 3H), 1.27 (s, 6H). |
10 mg (22%) | In ethyl acetate; | EXAMPLE 189 6-(5-Chloro-2-thienyl)-1,2-dihydro-2,2,4-trimethylquinoline (Compound 289, Structure 4 of Scheme II, where R1 =5-chloro-2-thienyl) This compound was prepared by General Method 2 (EXAMPLE 9) from Compound 9 (50 mg, 0.158 mmol) and 2-bromo-5-chlorothiophene (63 mg, 0.315 mmol). Purification by flash chromatography on silica gel (20 g) using 5% EtOAc:hexanes afforded 10 mg (22%) of Compound 289 as a yellow oil. Data for Compound 289: 1 H NMR (400 MHz, acetone-d6) 7.21 (d, J=2.1, 1H), 7.1 (dd, J=8.1, 2.0, 1H), 7.02 (d, J=3.7, 1H), 6.93 (d, J=3.7, 1H), 6.51 (d, 8.3, 1H), 5.42 (br s, 1H), 5.40 (s, 1H), 2.01 (s, 3H), 1.27 (s, 6H). |
10 mg (22%) | In ethyl acetate; | EXAMPLE 189 6-(5-Chloro-2-thienyl)-1,2-dihydro-2,2,4-trimethylquinoline (Compound 289, structure 4 of Scheme II, where R1 =5-chloro-2-thienyl) This compound was prepared by General Method 2 (EXAMPLE 9) from Compound 9 (50 mg, 0.158 mmol) and 2-bromo-5-chlorothiophene (63 mg, 0.315 mmol). Purification by flash chromatography on silica gel (20 g) using 5% EtOAc:hexanes afforded 10 mg (22%) of Compound 289 as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37.1% | <strong>[2873-18-9]2-Bromo-5-chlorothiophene</strong> (12.0 g, 60.8 mmol) and magnesium granule (1.48 g, 60.9 mmol) were suspended in anhydrous THF (30 mL), and the mixture was stirred at room temperature followed by being stirred under ice-cooling. To the reaction solution was dropped 1-ethoxycarbonyl-4-piperidone (6.95 g, 40.6 mmol), and anhydrous THF (20 mL) was added thereto, then the mixture was further stirred. To the reaction solution was added saturated aqueous ammonium chloride (186 mL), and the mixture was filtrated through Celite. The filtrate was concentrated, and water was added thereto, then the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. To the resulting residue was added ethyl acetate, and the precipitated crystals were filtered. The resulting crystals were washed with ethyl acetate to give 4-(5-chlorothiophene-2-yl)-1-ethoxycarbonyl-4-hydroxypiperidine (6.54 g, 37.1%) as light yellow crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; In pentane; | Intermediate 331.1 -Bis-(5-chloro-2-thienyl)-2-((3-e/?c/o)-8-methyl-8-aza-bicvclor3.2.1 ioct-3-vD- ethanol :The title compound was synthesized according to US 2,800,482, from {{3-endo)8- methyl-8-aza-bicyclo[3.2.1]oct-3-yl))-acetic acid methyl ester (0.338 g, 1.72 mmol) and <strong>[2873-18-9]2-bromo-5-chloro thiophene</strong> (395 mul, 3.6 mmol) and butyl lithium (2M in pentane, 1.8 ml, 3.6 mmol), yielding 0.470 g. Further purification was not performed. LC/MS (M+H): 402. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6% | With hexamethyldistannane;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; for 48h;Heating / reflux; | To a solution of 5-br?mo-2-{3-fluoro-2-[(phenylmethyl)oxy]phenyl}-6-methyl-3-(2- phenylethyl)-4(3H)-pyrimidinone (0.5 g, 1.01 mmoles) 11 in deoxygenated dioxane was added <strong>[2873-18-9]2-chloro-5-bromothiophene</strong> (0.2 g, 1.01 mmoles), tetrakistriphenylphosphine (0.18 g, 0.1 mmoles) and hexamethylditin (0.21 ml_, 1.01 mmoles). The reaction was refluxed for 48 h and concentrated. The crude residue was purified by chromatography on silica gel (Biotage) using ethylacetate and hexane mixtures (0-60%) to obtain the desired product (0.031 g) in 6% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; | Place N-[l-isopropyl-3-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-indol-6-yl]- methanesulfonamide (266 mg, 0.70 mmol), potassium carbonate (242 mg, 1.75 mmol), 2-bromo-5-chloro- thiophene (207 mg, 1.05 mmol), dioxane (6 mL) and water (1 mL), followed by addition of tetrakis(trirhohenylphosphine) palladium (0) (20 mg, 0.018 mmol) in a sealed tube under nitrogen. Heat the reaction mixture at 1000C overnight, then cool to room temperature. Dilute the reaction mixture with ethyl acetate, and sequentially wash the resulting mixture with water and brine. Dry the organic layer over <n="23"/>MgSO4. Chromatograph the crade residue on silica gel column eluting with hexane and ethyl acetate (gradient) to give 89 mg (34%) of the title compound. 1HNMR (CDCl3) delta 7.79 (d, IH, J= 8.8 Hz), 7.42 (d, IH, J= 1.8 Hz), 7.35 (s, 1 H), 6.97 (dd, IH, J= 2.0, 8.6 Hz), 6.93 (d, IH, J= 4.0 Hz), 6.88 (d, IH, J= 4.0 Hz), 4.50-4.67 (m, IH), 2.97 (s, 3H), 1.52 (d, 6H, J= 6.6 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; acetonitrile; for 3h;Heating / reflux; | To a solution of 2-fluoro-5-acetylphenylboronic acid (5.00 g, 27.48 mmol) in ACN (80 ml_) and H2O (20 ml_) were added 2-bromo-5-chlorothiophene (5.43 g, 27.48 mmol), sodium carbonate (2.91 g, 27.48 mmol) and tetrakis(triphenylphosphine)palladium(0) (635 mg, 0.02 mmol). The reaction mixture was refluxed for 3 h. After cooling, ethyl acetate (150 ml) and water (150 ml) were added. The aqueous phase was extracted with ethyl acetate and the combined organic phases were dried over sodium sulfate. Evaporation and purification of the crude product by silica gel chromatography using ethyl acetate/heptane gave the desired product (2.95 g , 42%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;copper(l) iodide; ethyl 2-oxocyclohexane carboxylate; In dimethyl sulfoxide; at 20 - 95℃; for 19.5h; | Example 39(3R)-N-[(2Z)-3-(5-chlorothien-2-yl)-5-(hydroxymethyl)-1,3-thiazol-2(3H)-ylidene]-3-fluoropyrrolidine-1-carboxamide; Example 36B (74 mg, 0.30 mmol), copper (I) iodide (12 mg, 0.06 mmol), and cesium carbonate (147 mg, 0.45 mmol) were added to a reaction vial with a septum-containing cap, and flushed with nitrogen three times. Then 2-bromo-5-chlorothiophene (39.5 muL, 0.36 mmol), ethyl 2-oxocyclohexanecarboxylate (19.5 muL, 0.12 mmol) and anhydrous dimethyl sulfoxide (0.30 mL) were added through the septum, the mixture was stirred 30 minutes at room temperature, and then heated at 95 C. in the dark for 19 hours. Then the mixture was quenched with concentrated aqueous ammonium hydroxide (0.60 mL), passed through diatomaceous earth with an ethyl acetate rinse, concentrated, and purified by reverse phase HPLC using an acetonitrile/water 10 mM ammonium acetate method to give the title compound.1H NMR (300 MHz, d4-MeOH) delta ppm 2.0-2.4 (2H), 3.45-4.1 (4H), 4.61 (2H), 5.20-5.48 (1H), 6.92 (1H), 7.11 (1H), 7.65 (1H); MS (ESI) m/z 362 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium acetate; bis(pinacol)diborane;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; dimethyl sulfoxide; at 90℃; for 16h;Inert atmosphere; | In a sealed tube were added a degassed mixture of the compound in Part C of Example 41 (50.0 mg, 0.121 mmol), 5,5,5',5'-tetramethyl-2,2'-bi(l,3,2- dioxaborinane) (38.4 mg, 0.170 mmol), 2-bromo-5-chlorothiophene (22.17 muL, 0.121 mmol) and potassium acetate (29.8 mg, 0.303 mmol) in a mixture of 1,4-dioxane (303 muL) and DMSO (303 muL). 1 , Y Bis(diphenylphisphino)ferrocenedichloro palladium(II) dichloride (7.98 mg, 10.91 mumol) was added and the reaction was allowed to stir at 90 0C for 16 h. Upon cooling, the reaction mixture was diluted with EtOAc (10 mL) and subsequently washed with water and brine. The organic layer was dried over anhydrous Na2SO4, concentrated, and purified by Prep. HPLC. The desired fraction was concentrated and lyophilized to afford 6.8 mg of the title compound as a light yellow solid: 1H NMR (400 MHz, CD3OD) delta 7.54 (1 H, d, J = 2.64 Hz), 7.32 (1 H, s), 7.25 (1 H, d, J= 3.95 Hz), 7.11 (1 H, dd, J= 8.57, 2.42 Hz), 6.93 - 7.06 (2 H, m), 4.88 (2 H, s), 3.89 (3 H, s), 3.79 (2 H, s), 1.32 (6 H, s); HPLC retention time: 3.896 min; LCMS (ES): m/z 450 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In tetrahydrofuran; at 60℃; for 16h;Inert atmosphere; | A mixture of 2-bromo-5-chlorothiophene (Aldrich, 163 mg; 0.82 mmol), te/f-butyl (4- chloro-2-ethynylphenoxy)acetate (Intermediate 3, 200 mg; 0.75 mmol), dichlorobis(triphenylphosphine)palladium(ll) (33 mg; 0.04 mmol), copper(l) iodide (8.6 mg; 0.04 mmol) was degassed during two minutes under nitrogen then THF (3 mL) and triethylamine (208 muL; 1.50 mmol) were added and reaction mixture was stirred at 60 0C for 16 hours. The solvent was evaporated and the residue was treated with an HCI solution (4 N in dioxane, 3.7 mL). After stirring for 16 hours, the solvents were removed under vacuum and the crude product purified by preparative HPLC. The title compound was obtained as a brown sticky solid.1H NMR (300MHz, DMSOd6) delta [ppm] 13.2 (1 H, bs), 7.57 (1 H, d, J= 2.7 Hz), 7.43 (1 H, dd, J= 9.0, 2.7 Hz), 7.31 (1 H, d, J= 4.0 Hz), 7.19 (1 H, d, J= 4.0 Hz), 7.00 (1 H, d, J= 9.0 Hz), 4.82 (2 H, s). MS (ESI+): 325.0. HPLC (Condition A): Rt 5.35 min (HPLC purity 96.4%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 4h;Inert atmosphere; Reflux; | A solution of (S)-methyl-3-methyl-2-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)dibenzo[b,d]thiophene-3-sulfonamido)butanoate (191 mg, 0.38 mmol), 2-bromo-5-chlorothiophene (165 mg, 92 mul, 0.836 mmol) and K2CO3 (132 mg, 0.95 mmol) in a mixture of DME/water (20:1), and the solution was degassed by bubbling nitrogen through for 10 minutes. Following the addition of Pd(PPh3)4, the reaction mixture was heated at reflux for 4 hours, then was cooled to RT, diluted with ethyl acetate, and washed with brine. The organic phase was dried over Na2SO4, concentrated under reduced pressure, and the crude residue was purified by flash column chromatography (hexane/AcOEt 85:15 to 7:3) to provide the desired product (88 mg, 47% yield) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Intermediate 844-(5-Chloro-thiophen-2-yl)-4-hydroxy-piperidine-l-carboxylic acid tert-butyl esterTo a cooled (-78 C) solution of 2-bromo-5-chlorothiophene (5.05 g, 25.60 mmol) in THF (35 mL) was added dropwise n-butyllithium (2.5 M in hexanes; 10.23 mL, 25.60 mmol) and the solution was stirred for 30 min under Argon. A solution of 4-oxo-piperidine-l- carboxylic acid tert-butyl ester (5 g, 25.10 mmol) in THF (9 mL) was added dropwise over 25 min while the temperature was maintained <-40 C and the solution was then allowed to warm to -20 C for 1.5 h, then 0 C for 1 h. The reaction mixture was quenched by addition of brine (7 mL) and then partitioned between water and EtOAc and the organic extract was washed with water, dried (Na2S04), and concentrated in vacuo. The crude product was crystallised from hot heptane/EtOAc to afford the title compound (6 g, 74%).LCMS (Method 2) Rt 4.54 min, m/z 340 [M+Na+]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With Pd(pi-crotyl)(QPhos)Cl; sodium t-butanolate; In toluene; at 25℃; for 20h;Inert atmosphere; | General procedure: A Schlenk flask was charged with the catalyst, NaOt-Buand aryl halide, if solid, and the flask was evacuated and backfilled with nitrogen three times. Subsequently, a solution of the aryl halide, if liquid, and the amine in toluene was added. The resulting reaction mixture was stirred under nitrogen at the indicated temperature and time (see Tables incommunication). The crude mixture was absorbed onto silica gel (Merck Silica Gel 60 (0.040-0.063 mm)) and purified by flash column chromatography (MTBE/40-60 petroleum ether eluent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With bis(triphenylphosphine)nickel(II) chloride; In tetrahydrofuran; for 24h;Inert atmosphere; Reflux; | General procedure: Into a 25 mL round-bottomed flask were added Pd(PPh3)2Cl2(0.028 g, 2.0 mol%), 2-iodobenzonitrile (0.22 g, 1.0 mmol), and I(4.0 mL, 0.5 M in THF, 2.0 mmol) under an argon atmosphere atr.t. The resulting mixture was stirred at r.t. for 1.0 h, quenchedwith 3 M HCl solution, then extracted with Et2O (3 × 10 mL),washed with sat. NaHCO3, Na2S2O3 solution and brine, and thendried over anhydrous MgSO4. Purification by column chromatographyon silica gel (EtOAc-heptane, 10:90) afforded 0.14 g of4a in 72% isolated yield as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 90℃; for 16h; | [0001251] To a stirred solution of Compound 175B (1.29 g, 4.24 mmol) in DMF (20 mL) and water (20 mL) was added Na2C03 (1.12 g, 10.6 mmol), Pd(PPh3)4 (247 mg, 0.21 mmol), and 2-bromo-5-chlorothiophene (838 mg, 4.24 mmol). The mixture was stirred under nitrogen at 90 C for 16 h. The reaction mixture was cooled to room temperature and purified with reverse phase chromatography using eluent (methanol in water (include 0.05% of NH3.H20), from 0% to 40% v/v) to afford Compound 359A. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; at 20℃; for 1h;Inert atmosphere; | General procedure: Preparation of 3-bromo-5-(4-cyanophenyl)-2-methylthiophene (2a): Into a 25mL round-bottomed flask were added Pd(PPh3)2Cl2 (0.035 g, 2.0 mol%), 4-bromobenzonitrile (0.36 g, 2.0 mmol), and 5.0 mL of 3-bromo-2-methylthiophen-5-ylzinc bromide(II) (0.5M in THF, 2.5mmol) under an argon atmosphere at room temperature. The resulting mixture was stirred at room temperature for 1.0 h. Quenched with 3M HCl solution, then extracted with ethyl ether (10 mL × 3). Washed with saturated NaHCO3, Na2S2O3 solution, and brine, and then dried over anhydrous MgSO4. Purification by column chromatography on silica gel (10% ethyl acetate/90% heptane) afforded 0.41 g of 2a in 73% isolated yield as a yellow solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.2% | With potassium phosphate; copper(l) iodide; 2-(N,N-dimethylamino)athanol; copper; at 80℃; for 72h; | Synthesis Example 78 (1476) 1-(4-Chlorobenzyl)-4-[4-(5-chlorothiophen-2-yl)piperazin-1-yl]-1,3,5-triazin-2(1H)-one (1477) An N,N-dimethylaminoethanol suspension (1 mL) of 1-(4-chlorobenzyl)-4-(piperazin-1-yl)-1,3,5-triazin-2(1H)-one (30 mg, 0.10 mmol) synthesized in Reference Synthesis Example 9, 2-bromo-5-chlorothiophene (110 muL, 0.10 mmol), copper (3.0 mg, 0.05 mmol), copper (I) iodide (9 mg, 0.05 mmol), and potassium phosphate (43 mg, 0.20 mmol) was stirred at 80 C. for 3 days. After the completion of the reaction, water was added to the reaction solution and extraction with ether and ethyl acetate from the resultant reaction solution was performed. The organic layer was washed with brine, was dried over anhydrous sodium sulfate, and was concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (ethyl acetate/methanol) to obtain the title compound (0.5 mg, yield: 1.2%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With tetrabutyl ammonium fluoride; palladium dichloride; In acetonitrile; at 70℃; under 7500.75 Torr; for 24h; | Palladium chloride (4.4 mg, 0.025 mmol) was weighed accurately, Tetrabutylammonium fluoride (183.0 mg, 0.7 mmol), <strong>[2873-18-9]2-chloro-5-bromothiophene</strong> (105.8 mg, 0.5 mmol) was added successively to a 25 mL autoclave, acetonitrile (5.0 mL) was added, trimethylallylsilane (97.6 mg, 0.6 mmol). And then charged with carbon dioxide to 1.0 MPa. The reaction vessel was placed in an oil bath at 70 C for 24 h. After completion of the reaction, the reaction vessel was slowly cooled to room temperature, and the remaining carbon dioxide was released. Finally, the solvent was removed under reduced pressure and the residue was isolated on a silica gel column using petroleum ether / ethyl acetate as the eluent. The yield of E-2-butenoic acid- (5-bromothiophene) -1-methyl ester was 86%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 100℃; for 8.16667h;Inert atmosphere; | A mixture of N-Boc-2-aminobenzeneboronic acid (2.37 g, 10.0 mmol), 2-bromo-5-chlorothiophene (2.17 g, 11.0 mmol), sodium carbonate (2.12 g, 20.0 mmol) and tetrakistriphenylphosphine palladium (0.57 g, 0.5 mmol) in 10% aq dioxane (75 mL) were degassed with nitrogen for 10 mins and then heated at 100 00 for 8 hrs. The cooled mixture was filtered and the filtrate concentrated to under reduced pressure and the residue treated with water (75 mL) and extracted with DCM (3 x 40 mL). The combined extracts were dried (MgSO4) and concentrated to dryness in vacuo. The crude product was purified by column chromatography (Biotage SNAP 100 g column, 20- 100%DCMihexane) to give a mixture of the title compound and the N-BOO intermediate. The mixture was dissolved in diethyl ether (25 mL) and treated with a 4M soln. of HCI in dioxane (3 mL) and stirred at r.t. for 0.75 hrs. The precipitate was collected by filtration washed with diethyl ether and dried at 40 00 under vacuum to give the title compound as a colourless solid (1 .35 g, 55%).1H NMR(ppm) (400 MHz, DMSO): 7.18 (IH, dd, J=7.2, 7.2 Hz) 7.27 (IH, d, J=3.8 Hz), 7.34 (1 H, d, J=7.3 Hz), 7.36 - 7.45 (3H, m) (NH2 not visible) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 80℃;Inert atmosphere; | General procedure: In a fume hood, an oven-dried Schlenk flask equipped with magnetic stirring bar was filled with N2 and evacuated (three cycles). Under N2 atmosphere, Pd(OAc)2 (1.1 mg, 0.005 mmol, 1 mol% Pd), SPhos (4.1mg, 0.01 mmol, 2 mol%), K3PO4 (160 mg, 1.5 mmol, 1.5 equiv), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,6-bis(trifluoromethyl)pyridine (1, 171 mg, 0.5 mmol, 1 equiv), aryl bromide (0.75 mmol,1.5 equiv), and DME (2 mL) were added in order. The Schlenk flask was closed and the mixture was heated at 80 C in an oil bath for 24-48 h. The progress of reaction was monitored by GC-MS and TLC. Upon completion of reaction, the Schlenk flask was cooled to r.t. and exposed to air. The mixture was extracted into EtOAc, washed with water and brine, and dried (anhyd Na2SO4). The crude product was purified by column chromatography (silica gel). For chloro-substituted bromoarenes (2g, 2h, and 2m), Pd(PPh3)4 (23mg, 0.02 mmol, 4 mol% Pd) was used (for 1-mmol scale reaction) in place of Pd(OAc)2 and SPhos. Unless otherwise noted, reactions were performed on a 0.5-mmol 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,6-bis(trifluoromethyl)pyridine (1) scale. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of 2-bromo-5-chlorothiophene (198 mg, 1 mmol) in dry THF (10 mL) at -78 C was dropped a solution of n-BuLi in THF (2.5 M, 0.4 mL, 1 mmol) over 5 minutes. After stirred at -78 C for 0.5 hour, to the mixture at -20oC was dropped a solution of Compound 4D (118 mg, 0.25 mmol) in anhydrous THF (5 mL). The mixture was stirred at 0 C for 2 hours, quenched with water (20 mL), and extracted with ethyl acetate (20 mL x 3). The combined organic layers was washed with brine (40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to afford a crude product, which was purified with preparative HPLC to furnish Compound 5: LC-MS (ESI) m/z: 527 [M+1]+;1H-NMR (CDCl3, 400 MHz): delta (ppm) 4.06 (s, 2H), 4.68 (s, 1H), 6.70 (d, J = 4 Hz, 1H), 6.74 (d, J = 4 Hz, 1H), 7.18 (d, J = 8.8 Hz, 2H), 7.29-7.33 (m, 4H), 7.39 (d, J = 8.8 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 50℃; for 5h;Inert atmosphere; | General procedure: To an oven dried 5 mL microwave vessel was addedPd(dppf)Cl2·CH2Cl2 (4 mol%), halide/pseudohalide (1 equiv),boron coupling partner (1 equiv), and Cs2CO3 (3 equiv). Thevessel was then capped and purged with N2 before addition ofCyrene (1 mL, 0.25 M) and H2O (1.8 mL). The reaction mixturewas heated to 50 C and maintained at this temperature withstirring for 5 h before the vessel was vented and decapped. Thesolution was then diluted with Et2O (10 mL) and washed withwater (2 × 20 mL) and brine (2 × 20 mL). The organics were thenpassed through a hydrophobic frit and concentrated underreduced pressure to give a residue, which was purified by flashchromatography (silica gel) to afford the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8.5 g | With sodium sulfide; In N,N-dimethyl-formamide; at 90℃; for 2h; | 2-Chloro-5-bromothiophene (10.0 g, 50.64 mmol) and sodium sulfide (3.95 g, 50.64 mmol) were added to N,N-dimethylformamide (100 ml), heated to 90 , stirring reaction 2 hour. The mixture was cooled in an ice-water bath, water (50 ml) was added, and a 2M hydrochloric acid solution was added dropwise to pH 5-6 under vigorous stirring, and the organic phase was combined, dried over anhydrous sodium sulfate, and concentrated to give the object. :2-chlorothiophene-5-thiol 8.5 g |
Tags: 2873-18-9 synthesis path| 2873-18-9 SDS| 2873-18-9 COA| 2873-18-9 purity| 2873-18-9 application| 2873-18-9 NMR| 2873-18-9 COA| 2873-18-9 structure
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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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