Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 18698-96-9 | MDL No. : | MFCD00046546 |
Formula : | C8H7IO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | IUHXGZHKSYYDIL-UHFFFAOYSA-N |
M.W : | 262.04 | Pubchem ID : | 2780090 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.12 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 50.7 |
TPSA : | 37.3 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.24 cm/s |
Log Po/w (iLOGP) : | 1.56 |
Log Po/w (XLOGP3) : | 2.33 |
Log Po/w (WLOGP) : | 1.92 |
Log Po/w (MLOGP) : | 2.55 |
Log Po/w (SILICOS-IT) : | 2.5 |
Consensus Log Po/w : | 2.17 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.56 |
Log S (ESOL) : | -3.2 |
Solubility : | 0.164 mg/ml ; 0.000625 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.75 |
Solubility : | 0.463 mg/ml ; 0.00177 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.13 |
Solubility : | 0.195 mg/ml ; 0.000745 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 0.0 |
Synthetic accessibility : | 1.62 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | 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 |
---|---|---|
With thionyl chloride; at 50℃; | General procedure: A solution of 3 g (13.8 mmol) of 2-(2-bromophenyl)-acetic in 10 mL ethanol was cooled to 0 ,and 1.6 ml (22 mmol) thionylchloride was added drop wise. The reaction mixture was heated to 50 . Over night.After cooling to room temperature the solvent was removed under reduced pressure. The residue was mixed withethyl acetate and filtered over 6 g basic aluminium oxide. The filtrate was evaporated under reduced pressure. 3.5g (89%) of the ethyl 2-(2-bromophenyl)acetate (1d) were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With borane; sodium hydrogencarbonate; acetic acid; In tetrahydrofuran; methanol; ethyl acetate; | STR164 Step 1--Preparation of 2-(2-Iodophenyl)ethanol. A solution of o-iodophenylacetic acid (19.87 g, 75.83 mmol) in dry tetrahydrofuran (110 mL) was added dropwise over 41 min to a solution of borane in tetrahydrofuran (151 mL of 1 M solution, ca. 151.0 mmol) which was cooled with an ice-water bath. The reaction was stirred at 0 to 10 C. for 2 hr 15 min. After the reaction mixture was cooled to 0 C., it was quenched by cautious addition (frothing|) of 10 (vol.) % acetic acid in methanol over 20 min. Stirring was continued for 25 min before the reaction was concentrated on a rotary evaporator. The residue was dissolved in ethyl acetate and washed with saturated ammonium chloride followed by saturated sodium bicarbonate. The organics were dried (Na2 SO4) and concentrated to a yellow oil (18.07 g) which was used in the next step without purification. TLC (hexane-ethyl acetate, 1:1): Rf =0.71; 1 H-NMR (DMSO-d6): delta 2.81 (t, J=7.2 Hz, 2H), 3.53 (dt, J=5.1 Hz, 7.5 Hz, 2H), 4.73 (t, J=5.4 Hz, 1H), 6.90-6.95 (m, 1H), 7.29 (dd, J=4.9 Hz, 0.8 Hz, 2H), 7.79 (d, J=7.7 Hz, 1H); MS (EI) 248 [M]+ (C8 H9 IO, FW=248.07). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With triethylamine In acetic anhydride at 100℃; for 9h; | |
90% | With acetic anhydride; triethylamine at 100℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | Stage #1: 4-methylsulfanyl-thiophenol; o-iodophenylacetic acid With copper; potassium hydroxide In water for 48h; Reflux; Inert atmosphere; Stage #2: With hydrogenchloride In water at 20℃; Inert atmosphere; | |
With potassium hydroxide In water for 18h; Heating; Yield given; | ||
With copper; potassium hydroxide In water at 50℃; for 24h; Reflux; | 4.2.28 Dibenzo[b,f]thiepin-10(11H)-one (38a) General procedure: KOH (722mg, 12.9mmol, 3.3equiv.) was dissolved in 7.8mL of water, benzenethiol (35a) (0.40mL, 3.90mmol, 1.0equiv.) was added and the mixture was heated to 50°C. Copper powder (74mg, 1.17mmol, 0.3equiv.) and 2-(2-iodophenyl)acetic acid (36) (980mg, 3.74mmol, 0.96equiv.) was added. The reaction mixture was stirred at reflux for 24h, then cooled to room temperature. The yellow precipitate was filtered off, and the filtrate was acidified with HClaq. (1M). The aqueous phase was extracted with EtOAc (5×). The organic phases were united, washed with brine, dried over Na2SO4, filtered and the solvent was removed under reduced pressure. Thus were obtained 1.20g (100% plus impurities) of 2-(2-(phenylthio)phenyl)acetic acid (37a) as a yellow solid; the crude was used in the next step without further purification. (0098) 4g of oily P2O5 was heated to 150°C under stirring. The crude 2-(2-(phenylthio)phenyl)acetic acid (37a) was added in little portions and the mixture was stirred at 150°C for 4h, then cooled to room temperature. Ice and water were carefully added, and the resulting aqueous solution was extracted with EtOAc (5×). The organic phases were united, washed with brine, dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The crude residue was purified by flash chromatography (eluent Hexane/EtOAc=97/3 to 9/1), yielding 403mg (46%) of dibenzo[b,f]thiepin-10(11H)-one (38a) as a green-yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With potassium hydroxide; copper atom In water monomer Heating; | |
With potassium hydroxide; copper atom Heating; | ||
Stage #1: 3-Methoxybenzenethiol With potassium hydroxide In water monomer at 50℃; for 0.166667h; Stage #2: 2-(2-iodophenyl)acetic acid With copper atom In water monomer Reflux; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 3h; Inert atmosphere; | xxxv.a a) 2-(2-Iodophenyl)acetyl chloride I103 To a solution of 2-(2-iodophenyl)acetic acid (15.7 g, 60 mmol) and DMF (3 drops) in DCM (100 mL) at 0 °C under N2 was added oxalyl chloride (23 g, 180 mmol) dropwise and the mixture was stirred for 3 h. The mixture was concentrated under reduced pressure to give the title compound (16.8 g, 100%) as a brown oil. LCMS-D: Rt 2.14 min, m/z 276.9 [M- CI+MeO+H]+. |
90% | With thionyl chloride In benzene | 3 Preparation of N,N-dimethyl-o-iodophenylacetamide EXAMPLE 3 Preparation of N,N-dimethyl-o-iodophenylacetamide To 10 g (0.038 mole) of o-iodophenylacetic acid was added 50 ml of a solution of 5.7 g (0.048 mole) of thionyl chloride in anhydrous benzene, and the mixture was refluxed for 2 hours under agitation. Then, the solvent and unreacted thionyl chloride were removed by distillation under reduced pressure below 40° C. and the residue was subjected to distillation under reduced pressure to obtain 9.6 g of o-iodophenylacetyl chloride as a light yellow oily product having a boiling point of 153° to 156° C. under 8 mmHg in a yield of 90%. |
With thionyl chloride |
With thionyl chloride In benzene Heating; | ||
With thionyl chloride for 2h; Heating; | ||
With thionyl chloride In dichloromethane for 4h; Heating; | ||
2.60 g | With thionyl chloride for 12h; Ambient temperature; | |
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h; | ||
With thionyl chloride for 2h; Heating; | ||
With phosgene; N,N-dimethyl-formamide In dichloromethane at 25℃; | ||
With oxalyl dichloride In dichloromethane at 20℃; for 0.5h; | ||
With thionyl chloride at 100℃; for 3h; | ||
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 0.5h; | ||
With thionyl chloride at 45 - 50℃; for 2h; Inert atmosphere; | ||
With thionyl chloride at 100℃; for 3h; | ||
With thionyl chloride for 2h; Reflux; | ||
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; Inert atmosphere; | ||
With oxalyl dichloride In dichloromethane at 20℃; for 2h; | I1.1 Step 1 : (N,N)-Diisopropyl 2-iodophenylacetamide; To a solution of 2-iodophenylacetic acid (1 1.0 g, 42.0 mmol, commercially available) in dichloromethane (85 mL) was added oxalyl chloride (7.11 mL, 84 mmol) followed by 2 drops of dimethyl formamide. The solution as stirred at room temperature for 2 h and the solvents were removed in vacuo. The residue was taken up in dichloromethane (100 mL) and cooled at 0 °C. Diisopropylamine (17.6 mL, 126 mmol) was then added and the solution as warmed to room temperature. The solvents were removed in vacuum. The residue was partitioned between ethyl acetate and water and extracted with ethyl acetate. The combined organic layers were washed with hydrogen chloride (IN), brine, dried and concentrated to give 14.3 g of (N,N)-Diisopropyl 2-iodophenylacetamide (White solid, 99%). Ci4H20INO, MW: 345.23; LCMS (method A) RT 1.90 min; Mass 346 (100%, MH+), 268 (10 %, MNa+); IR: 2965, 1634, 1438, 1369, 1337 cm"1; 1H NMR (400 MHz, CDC13) δ 7.84 (d, 1 H), 7.22 - 7.35 (m, 3 H), 6.84 - 6.97 (m, 1 H), 3.91 (m, 1 H), 3.76 (s, 2 H), 3.43 (m, 1 H), 1.46 (d, 3 H), 1.15 (d, 6 H) ppm. | |
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane | ||
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane | ||
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide | ||
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 2h; | ||
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h; | General procedure for acid chloride formation (step f) General procedure: Toan oven-dried round bottom flask charged with 2-(4-chlorophenyl)acetic acid,56(500 mg, 2.93 mmol, 1.0 equiv.),and CH2Cl2(10 mL) was added oxalyl chloride(0.30 mL, 3.52mmol, 1.2 equiv.) dropwise followed by DMF (0.02 mL).The resulting mixture was allowed to stir at room temperature for 2 h.The solvent was removed under reduced pressure to give a yellow oily residue which was dissolved in THF (10 mL). | |
With thionyl chloride for 3h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With copper; potassium carbonate In N,N-dimethyl-formamide at 150℃; for 7h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With copper; potassium hydroxide In water for 24h; Reflux; | |
With potassium hydroxide | ||
With copper; potassium hydroxide In water at 50℃; for 24h; Reflux; | 4.2.28 Dibenzo[b,f]thiepin-10(11H)-one (38a) General procedure: KOH (722mg, 12.9mmol, 3.3equiv.) was dissolved in 7.8mL of water, benzenethiol (35a) (0.40mL, 3.90mmol, 1.0equiv.) was added and the mixture was heated to 50°C. Copper powder (74mg, 1.17mmol, 0.3equiv.) and 2-(2-iodophenyl)acetic acid (36) (980mg, 3.74mmol, 0.96equiv.) was added. The reaction mixture was stirred at reflux for 24h, then cooled to room temperature. The yellow precipitate was filtered off, and the filtrate was acidified with HClaq. (1M). The aqueous phase was extracted with EtOAc (5×). The organic phases were united, washed with brine, dried over Na2SO4, filtered and the solvent was removed under reduced pressure. Thus were obtained 1.20g (100% plus impurities) of 2-(2-(phenylthio)phenyl)acetic acid (37a) as a yellow solid; the crude was used in the next step without further purification. (0098) 4g of oily P2O5 was heated to 150°C under stirring. The crude 2-(2-(phenylthio)phenyl)acetic acid (37a) was added in little portions and the mixture was stirred at 150°C for 4h, then cooled to room temperature. Ice and water were carefully added, and the resulting aqueous solution was extracted with EtOAc (5×). The organic phases were united, washed with brine, dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The crude residue was purified by flash chromatography (eluent Hexane/EtOAc=97/3 to 9/1), yielding 403mg (46%) of dibenzo[b,f]thiepin-10(11H)-one (38a) as a green-yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With [bis(acetoxy)iodo]benzene; iodine; palladium diacetate In N,N-dimethyl-formamide at 60℃; for 12h; Darkness; | |
With potassium iodide; thallium(III) trifluoroacetate | ||
With [bis(acetoxy)iodo]benzene; iodine; palladium diacetate In N,N-dimethyl-formamide at 60℃; for 24h; Inert atmosphere; |
With [bis(acetoxy)iodo]benzene; iodine; palladium diacetate In N,N-dimethyl-formamide at 60℃; for 12h; Inert atmosphere; Darkness; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide; copper atom | ||
With copper atom; potassium hydroxide In water monomer at 140℃; for 0.2h; Microwave irradiation; | ||
Stage #1: 4-Methoxybenzenethiol With potassium hydroxide In water monomer at 50℃; for 0.166667h; Stage #2: 2-(2-iodophenyl)acetic acid With copper atom In water monomer Reflux; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | ||
83% | With (2,2'-bipyridine)nickel(II) dibromide In ethylene glycol at 150℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With sodium borodeuteride; boron trifluoride diethyl etherate In tetrahydrofuran Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With 2,2'-azobis(isobutyronitrile); triphenylstannane; sodium hydrogencarbonate In water at 90℃; for 6h; | |
Stage #1: o-iodophenylacetic acid With potassium <i>tert</i>-butylate; 1-acetyladamantane In ammonia for 1h; Inert atmosphere; Cooling; Irradiation; liquid NH3; Stage #2: With nitric acid In water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In acetonitrile for 15h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With copper; potassium hydroxide In water at 140℃; for 0.2h; Microwave irradiation; | |
67% | With potassium hydroxide; copper In water for 12h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sulfuric acid at 65℃; for 2.5h; | |
100% | With thionyl chloride at 60℃; for 1h; | |
100% | With sulfuric acid at 0℃; for 2h; |
99% | With hydrogenchloride In water monomer at 20℃; for 4h; | |
99% | With sulfuric acid at 80℃; for 16h; Inert atmosphere; | a 2-(2-lodophenyl)acetic acid (5.00 g, 19.1 mmol) was placed into a reaction flask and dissolved in MeOH (150 mL). Sulfuric acid (250 pL) was added and reaction mixture was stirred and heated at 80 "C under nitrogen for 16 hours. The resulting mixture was cooled to room temperature and the volatiles removed by evaporation under reduced pressure. The residue was taken up in ethyl acetate (100 mL), washed with 10% NaHC03 (100 mL), dried (MgS04) and evaporated under reduced pressure to give the title compound (/9) (5.20g, 99%) as a clear liquid; 1H NMR (400 MHz, CDCI3) δ 7.85 (dd, J = 7.9, 1 .0 Hz, 1 H), 7.35 - 7.27 (m, 2H), 6.97 (ddd, J = 7.9, 7.0, 2. Hz, 1 H), 3.81 (s, 2H), 3.72 (s, 3H). |
99% | With sulfuric acid In water monomer at 80℃; for 16h; Inert atmosphere; | |
99% | With sulfuric acid at 80℃; for 16h; Inert atmosphere; | a Methyl 2-(2-iodophenyl)acetate (19) 2-(2-iodophenyi)acetic acid (5.00 g, 19.1 mrnoi) was placed into a reaction flask and dissolved in MeOH (150 mL). Sulfuric acid (250 L) was added and reaction mixture was stirred and heated at 80 °C under nitrogen for 16 hours. The resulting mixture was cooled to room temperature and the volatiles removed by evaporation under reduced pressure. The residue was taken up in ethyl acetate (100 mL), washed with 10% NaHC03 (100 mL), dried (MgS04) and evaporated under reduced pressure to give the title compound (19) (5,20g, 99%) as a dear liquid; 1 H NMR (400 MHz, CDCI3) δ 7.85 (dd, J = 7.9, 1.0 Hz, 1 H), 7.35 - 7.27 (m, 2H), 6.97 (ddd, J = 7.9, 7.0, 2.1 Hz, 1 H), 3.81 (s, 2H), 3.72 (s, 3H). |
98% | With boron trifluoride diethyl ether complex at 60℃; for 2h; | |
98% | With dmap; dicyclohexyl-carbodiimide at 20℃; Inert atmosphere; | |
96% | With sulfuric acid at 85℃; for 2h; | 12.1 Step 1: methyl 2-(2-iodophenyl)acetate [0221] To a solution of 2-(2-iodophenyl)acetic acid (3.67g, 14 mmol) in MeOH (35mL) was added 2 mL of concentrated H2SO4. The reaction was stirred at 85 °C for 2 hours, then concentrated in vacuo, adjusted to pH=7~8 with sat.NaHCO3 solution and extracted with EtOAc (2x 30mL). The combined organic phase was washed with brine, dried over Na2SO4 and concentrated to give the desired product methyl 2-(2-iodophenyl)acetate (3.7g) as an orange oil. Yield 96% (ESI 277 (M+H)+). |
95% | With sulfuric acid for 3h; Reflux; | |
95% | With thionyl chloride at 60℃; for 1h; | 1 2-Allyl- 1 -(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-((2-methyl-2,3-dihydro- 1 H-spiro[cyclopropane- 1,4-isoquinolin] -7-yl)amino)- 1 ,2-dihydro-3H-pyrazolo[3 ,4-d]pyrimidin-3-one 2-(2-Iodophenyl)acetic acid (100 g, 381.67 mmol) was dissolved in MeOH (400 mL). SOC12 (34 mL, 458.01 mmol) was added at RT with stifling, and the reaction mixture was heated at 60 °C for 1 h. The solvent was removed in vacuo. The resulting crude material was dissolved in ethyl acetate (250 mL), washed with saturated NaHCO3 (1 x 100 mL), brine (1 x 100 mL) and dried (Na2SO4). The solvent was removed to afford methyl 2-(2- iodophenyl)acetate (100 g, 95%) as a brown oil. MS (ESI) mlz 276.9 [M+H]. |
92.6% | With sulfuric acid at 65℃; for 2.5h; | |
91% | With toluene-4-sulfonic acid In dichloromethane at 20℃; | |
86% | Stage #1: 2-(2-iodophenyl)acetic acid With thionyl chloride; N,N-dimethyl-formamide In dichloromethane for 3h; Reflux; Stage #2: methanol for 4h; Reflux; | |
84% | With thionyl chloride at 60℃; for 1h; Inert atmosphere; Schlenk technique; | |
With sulfuric acid for 2.5h; Heating; | ||
With sulfuric acid for 3h; Inert atmosphere; Reflux; | ||
With thionyl chloride at 0 - 30℃; for 6h; | ||
With sulfuric acid at 0℃; for 3.16667h; Reflux; Inert atmosphere; | ||
With sulfuric acid for 6h; Reflux; | ||
With thionyl chloride at 0℃; for 4h; Reflux; | ||
With sulfuric acid at 90℃; for 6h; Inert atmosphere; | ||
With sulfuric acid for 18h; Cooling with ice; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | Stage #1: o-iodophenylacetic acid With thionyl chloride at 40℃; for 2h; Stage #2: aniline With water; potassium carbonate In ethyl acetate at 20℃; for 1h; | |
93% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In acetonitrile at 20℃; for 24h; | |
53% | Stage #1: o-iodophenylacetic acid With thionyl chloride In dichloromethane at 50℃; for 4h; Inert atmosphere; Stage #2: aniline In ethyl acetate for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Stage #1: o-iodophenylacetic acid With chloromethyl polystyrene; cross-linked with divinylbenzene; potassium carbonate In N,N-dimethyl-formamide at 85℃; for 24h; Stage #2: m-tolylboronic acid With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 144h; Stage #3: With sodium hydroxide In methanol; water for 48h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | Stage #1: o-iodophenylacetic acid With chloromethyl polystyrene; cross-linked with divinylbenzene; potassium carbonate In N,N-dimethyl-formamide at 85℃; for 24h; Stage #2: 2-Methoxyphenylboronic acid With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 144h; Stage #3: With sodium hydroxide In methanol; water for 48h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | Stage #1: o-iodophenylacetic acid With chloromethyl polystyrene; cross-linked with divinylbenzene; potassium carbonate In N,N-dimethyl-formamide at 85℃; for 24h; Stage #2: 3-acetylphenylboronic acid With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 144h; Stage #3: With sodium hydroxide In methanol; water for 48h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: o-iodophenylacetic acid With thionyl chloride at 40℃; for 2h; Stage #2: With ammonia; water; potassium carbonate In ethyl acetate at 20℃; for 1h; | |
89% | Stage #1: o-iodophenylacetic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1h; Stage #2: With ammonium hydroxide In tetrahydrofuran for 0.5h; | 40.a a) 2-(2-Iodophenyl)acetamide (A24) 2-Iodophenylacetic acid (2.62 g, 10.0 mmol), DCM (50 mL), oxalyl chloride (1.03 mL, 12.0 mmol) and DMF (0.05 mL) were stirred at room temperature. After one hour the mixture was concentrated in vacuo. The residue was dissolved in THF (50 mL) and a concentrated solution of aqueous ammonia (50 mL) added. The mixture was stirred for thirty min and concentrated in vacuo. The residue was slurried in water (100 mL), filtered, the collected solid washed with water (2 χ 50 mL) and air dried to give the product as a tan solid (2.33 g, 89% yield). 1H NMR (400 MHz, Chloroform-d) δ 7.90 - 7.86 (m, 1H), 7.40 - 7.33 (m, 2H), 7.03 - 6.96 (m, 1H), 5.42 (brs, 2H), 3.75 (s, 2H). LCMS-A RT 4.88 min; m/z 262.0 [M+H]+. |
88% | With ammonium carbonate; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 17h; Inert atmosphere; | 8.c 2-lodophenylacetic acid (2.00 g, 7.63 mmol) was dissolved in dry THF (70 mL) and dry DMF (10 mL) under an atmosphere of nitrogen. To the solution were added 1 - hydroxybenzotriazole (1.134 g, 8.396 mmol) and EDCI (1 .609 g, 8.396 mmol) and /V,/V-diisopropylethylamine (5.318 mL, 30.53 mmol) and the reaction mixture was stirred at room temperature for 10 minutes. Ammonium carbonate (2.933 g, 30.53 mmol) was added in one portion, and the reaction was stirred room temperature for 7 hours. The volatiles were removed in vacuo and the residual solution was diluted with EtOAc (150 mL) and sat. aq. NaHC03 (100 mL). The layers were separated and the organic layer were washed with water (100 mL), brine (100 mL), dried (MgSO„), filtered and concentrated in vacuo to give the title compound (138) (1.755 g, 88% yield) as a beige solid; 1H NMR (400 MHz, cfe-DMSO) δ 7.82 (dd, J = 7.9, 0.9 Hz, 1 H), 7.42 (s, 1 H), 7.36 - 7.28 (m, 2H), 7.02 - 6.94 (m, 2H), 3.55 (s, 2H). LCMS Method C: Π 4.77 min; m/z 262.0 [M+H]+. |
88% | Stage #1: o-iodophenylacetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 0.166667h; Inert atmosphere; Stage #2: With ammonium carbonate In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 17h; Inert atmosphere; | 8.c 2-(2-lodophenyl)acetamide (138) 2-iodophenyiacetic acid (2.00 g, 7.83 mrnoi) was dissolved in dry THF (70 mL) and dry D F (10 mL) under an atmosphere of nitrogen. To the solution were added 1- hydroxybenzotriazole (1 , 134 g, 8.396 mmol) and EDCI (1.609 g, 8.396 mmol) and W,A -diisopropylethylamine (5.318 mL, 30.53 mmol) and the reaction mixture was stirred at room temperature for 10 minutes. Ammonium carbonate (2.933 g, 30.53 mmol) was added in one portion, and the reaction was stirred room temperature for 17 hours. The volatiles were removed in vacuo and the residual solution was diluted with EtOAc (150 mL) and sat. aq. NaHC03 (100 mL). The layers were separated and the organic layer were washed with water (100 mL), brine (100 mL), dried (MgS04), filtered and concentrated in vacuo to give the title compound (138) (1.755 g, 88% yield) as a beige solid; H N R (400 MHz, e/g-DMSG) δ 7,82 (dd, J = 7.9, 0.9 Hz, 1 H), 7.42 (s, 1 H), 7.36 - 7.28 (m, 2H), 7.02 - 6.94 (m, 2H), 3.55 (s, 2H). LC S Method C: rt 4.77 min; m/z 262.0 [M+H]+. |
63% | Stage #1: o-iodophenylacetic acid With thionyl chloride at 75℃; for 3h; Stage #2: With ammonium carbonate In dichloromethane at 60℃; for 20h; | |
60% | Stage #1: o-iodophenylacetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 0.166667h; Inert atmosphere; Stage #2: With ammonium carbonate In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; | Intermediate A1 : 2-(2-iodophenyl)acetamide 1 -Hydroxybenzotriazole (2.58 g, 19.1 mmol), EDCI (2.96 g, 19.1 mmol) and diisopropylethylamine (12.1 mL, 69.3 mmol) were added sequentially to a solution of 2-(2- iodophenyl)acetic acid (4.54 g, 17.3 mmol) in DMF (22 mL) and THF (151 mL) under a N2 atmosphere. The reaction mixture was allowed to stir at rt for 10 min. Ammonium carbonate (6.66 g, 69.3 mmol) was then added in one portion to the reaction mixture, which was then left to stir at rt overnight. The mixture was cone, in vacuo and water was added. The mixture was extracted with EtOAc, washed with H20, sat. aq. NaHC03 sol. and brine before drying over MgS04 and cone, in vacuo. The solid was suspended in EtOAc before being collected by vacuum filtration to give the title compound as an off-white solid (2.73 g, 60 %). LCMS (Method 1 ) Rt 1.859 min. |
40.2% | With 4-methyl-morpholine; ammonia; HATU In 1,4-dioxane; N,N-dimethyl-formamide for 16h; | 107 2-(2-Iodophenyl)acetamide (107-2). HATU (50.8 g, 134 mmol) was added to a stirred solution of 107-1 (28 g, 107 mmol), NH3 (321 ml, 160 mmol, 0.5 M/dioxane), iV-methylmorpholine (23.5 ml, 214 mmol) in . DMF (300 ml). The mixture was stirred for 16 hours and then was diluted with EtOAc and washed with H2O, sat NaHCO3, brine, dried over anhydrous MgSO4, filtered and 2/3 solvent was removed in vacuo. The solid was collected, washed with diethyl ether and dried in vacuo to afford 29-2 11.2g, 40.2%) as a white solid.1H NMR (500 MHz, CDCl3) δ7.i (d, 1 H, J = 8 Hz), 7.36 (m, 2 H), 7.00 (m, 1 H), 5.38 (s, 2 H), 3.75 (s, 2H). |
Multi-step reaction with 2 steps 1: thionyl chloride / CH2Cl2 / 4 h / Heating 2: conc. ammonium hydroxide | ||
Multi-step reaction with 2 steps 1: thionyl chloride / 2 h / Heating 2: 54 percent / aq. NH3 / dioxane / Ambient temperature | ||
Multi-step reaction with 2 steps 1: thionyl chloride / 2 h / Reflux 2: ammonia / dichloromethane / 2 h | ||
Multi-step reaction with 2 steps 1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C 2: ammonia / tetrahydrofuran / 12 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With lithium perchlorate In acetonitrile at 26.85℃; Electrochemical reaction; | |
96% | With lithium perchlorate; silver; silver(l) oxide In water; acetonitrile at 26.85℃; Electrochemical reaction; | |
Multi-step reaction with 2 steps 1: Et3N, PhCO2Ag 2: aq. NaOH |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Stage #1: o-iodophenylacetic acid With thionyl chloride at 40℃; for 2h; Stage #2: methylamine With water; potassium carbonate In ethyl acetate at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With copper; potassium hydroxide In water for 24h; Reflux; | |
94% | With copper; potassium hydroxide In water at 100℃; Irradiation with microwave; | 22.1-bis A suspension of 2-iodophenyl acetic acid (1 g, 3.82 mmol), 4-bromobenzenethiol (0.722 g, 3.82 mmol), KOH (0.427 g, 7.63 mmol) and copper powder (24 mg, 0.38 mmol) in 2 mL of water, was allowed to react in microwave (conditions: 2×6 min, 180 W, T max=100° C., P max=100 psi). The suspension obtained was dissolved in 2N aqueous solution of KOH and then filtered. The filtrate was acidified with 1N aq. HCl; the white precipitate was filtered, dried in vacuo, purified by trituration with acetone to give the pure acid 1-bis as white solid (1.16 g, 94%).1H-NMR (CDCl3, 200 MHz): 7.44 (d, J=7 Hz, 1H); 7.36-7.26 (m, 5H); 7.01 (d, J=8.4 Hz, 2H); 3.86 (s, 2H).Anal. Calcd. for C14H11BrO2S (MW=323.2): C, 52.03; H, 3.43; Br, 24.72; O, 9.90; S, 9.92. |
88% | With potassium hydroxide; copper In water at 100℃; for 0.2h; Microwaves; | 22.1-bis (1-bis) A suspension of 2-iodophenyl acetic acid (Ig, 3.82 mmol), 4-bromobenzenethiol (0.722 g, 3.82 mmol), KOH (0.427 g, 7.63 mmol) and copper powder (24 mg, 0.38 mmol) in 2 mL of water, was allowed to react in microwave(conditions: 2x 6 min, 180 W, T max=100°C, P max=100 psi) .The suspension obtained was dissolved in 2N aqueous solution of KOH and then filtered. The filtrate was acidified with IN aq. HCl; the white precipitate was filtered, dried in vacuo, purified by trituration with acetone to give the pure acid 1-bis as white solid (l.lδg, 94%) .1H-NMR (CDCl3, 200MHz): 7.44 (d, J= 7Hz, IH); 7.36-7.26 (m, 5H); 7.01 (d, J= 8.4Hz, 2H); 3.86 (s, 2H). Anal. Calcd. for Ci4H11BrO2S (MW=323.2): C 52.03; H 3.43; Br 24.72; O 9.90; S 9.92.; Example 62- (2-biphenyl-4-ylthio) phenyl) acetic acid (19a), 2- (2- (4- methoxyphenylthio) phenyl) acetic acid (19b), 2- (2-biphenyl-4- ylthio) phenyl) -N-hydroxyacetamide (21a), N-hydroxy-2- (2- (4- methoxyphenylthio) phenyl) acetamide (21b) and 2- (2- (4- (but-2- iniloxy) phenylthio) phenyl) -N-hydroxyacetamide (21c); (16) Compound 16 was synthesized according to the procedure described for the preparation of 10, starting from o-iodophenylacetic acid (5 g, 19.08 mmol) and 4- bromobenzenethiol (2.4 g, 19.08 mmol) into 5 portions of 1 g each. The obtained suspension was collected and diluted in KOH 2N. The obtained suspension was filtered and acidified with HCl IN. The formed precipitate was brought to dryness under reduced pressure at 500C. There were recovered 4.37 g of 16 (88%, white solid) . 1H-NMR (de-DMSO, 200MHz ) : 3 . 74 ( s , 2H) , 7 . 07 (d, J=8Hz , 2H) , 7 . 30 -7 . 42 (m, 4H) 7 . 4 9 (d, J=8Hz , 2H) , 12 . 34 (br . s , IH) . |
77% | With copper; potassium hydroxide In water at 140℃; for 0.2h; Microwave irradiation; | |
With copper; potassium hydroxide In water at 140℃; for 0.2h; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 100 percent / sulfuric acid / 2.5 h / 65 °C 2: 90 percent / PPh3; triethylamine / CuI; PdCl2(PPh3)2 / tetrahydrofuran / 12 h / 20 °C 3: 88 percent / potasssium carbonate / methanol; ethanol | ||
Multi-step reaction with 3 steps 1: H2SO4 / 2.5 h / Heating 2: Et2NH; CuI / PdCl2(PPh3)2 / tetrahydrofuran / 1.5 h / 20 °C 3: TBAF / CH2Cl2 / 0.33 h / 20 °C | ||
Multi-step reaction with 3 steps 1: sulfuric acid / 16 h / 80 °C / Inert atmosphere 2: triethylamine / copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride / tetrahydrofuran / 16 h / 20 °C / Inert atmosphere 3: tetrabutyl ammonium fluoride / dichloromethane; tetrahydrofuran / 1 h / 0 - 20 °C |
Multi-step reaction with 3 steps 1: sulfuric acid / water / 16 h / 80 °C / Inert atmosphere 2: copper(l) iodide; triethylamine; bis-triphenylphosphine-palladium(II) chloride / tetrahydrofuran / 16 h / 20 °C 3: tetrabutyl ammonium fluoride / tetrahydrofuran; dichloromethane / 1 h / 0 - 20 °C | ||
Multi-step reaction with 3 steps 1: sulfuric acid / 16 h / 80 °C / Inert atmosphere 2: trans-bis(triphenylphosphine)palladium dichloride; copper(l) iodide; triethylamine / tetrahydrofuran / 16 h / 20 °C / Inert atmosphere 3: tetrabutyl ammonium fluoride / dichloromethane / 1 h / 0 - 20 °C | ||
Multi-step reaction with 3 steps 1: sulfuric acid / 6 h / 90 °C / Inert atmosphere 2: bis-triphenylphosphine-palladium(II) chloride; triethylamine; copper(l) iodide / 12 h / 20 °C / Inert atmosphere 3: potassium fluoride / methanol / 1 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 100 percent / sulfuric acid / 2.5 h / 65 °C 2: 90 percent / PPh3; triethylamine / CuI; PdCl2(PPh3)2 / tetrahydrofuran / 12 h / 20 °C | ||
Multi-step reaction with 2 steps 1: H2SO4 / 2.5 h / Heating 2: Et2NH; CuI / PdCl2(PPh3)2 / tetrahydrofuran / 1.5 h / 20 °C | ||
Multi-step reaction with 2 steps 1: sulfuric acid / 16 h / 80 °C / Inert atmosphere 2: triethylamine / copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride / tetrahydrofuran / 16 h / 20 °C / Inert atmosphere |
Multi-step reaction with 2 steps 1: sulfuric acid / water / 16 h / 80 °C / Inert atmosphere 2: copper(l) iodide; triethylamine; bis-triphenylphosphine-palladium(II) chloride / tetrahydrofuran / 16 h / 20 °C | ||
Multi-step reaction with 2 steps 1: sulfuric acid / 16 h / 80 °C / Inert atmosphere 2: trans-bis(triphenylphosphine)palladium dichloride; copper(l) iodide; triethylamine / tetrahydrofuran / 16 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: sulfuric acid / 6 h / 90 °C / Inert atmosphere 2: bis-triphenylphosphine-palladium(II) chloride; triethylamine; copper(l) iodide / 12 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With trimethylsilyl bromide; 1,1,3,3-Tetramethyldisiloxane; indium tribromide In chloroform at 60℃; for 1h; Sealed tube; Inert atmosphere; | |
Multi-step reaction with 2 steps 1: 60 percent / lithiumaluminiumhydride / tetrahydrofuran / 0 - 20 °C 2: 90 percent / phosphorus tribromide / 2 h / 80 °C | ||
Multi-step reaction with 2 steps 1: BH3 / tetrahydrofuran 2: P(Ph)3Br2 / CH2Cl2 |
With indium(III) bromide; 1,1,3,3-Tetramethyldisiloxane; trimethylsilyl cyanide In chloroform at 60℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: oxalyl chloride; DMF / CH2Cl2 / 2 h / 20 °C 2: 0.46 g / CH2Cl2; H2O / 1 h / 0 °C | ||
Multi-step reaction with 2 steps 1: thionyl chloride / 2 h / Reflux 2: dichloromethane / 2 h | ||
Multi-step reaction with 2 steps 1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane 2: dichloromethane / 0 °C |
Multi-step reaction with 2 steps 1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane 2: dichloromethane / 0 °C | ||
Multi-step reaction with 2 steps 1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide 2: dichloromethane / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With indium(III) bromide; 1,1,3,3-Tetramethyldisiloxane; iodine In chloroform at 20 - 60℃; for 1.08333h; Sealed tube; Inert atmosphere; | |
Multi-step reaction with 3 steps 1: BH3*SMe2 / tetrahydrofuran / 0 - 20 °C 2: Et3N / CH2Cl2 / 0 - 20 °C 3: NaI / acetone / Heating | ||
Multi-step reaction with 3 steps 1: 93 percent / borane-dimethyl sulfide complex / tetrahydrofuran / Ambient temperature 2: 96 percent / Et3N / CH2Cl2 / 2 h / Ambient temperature 3: 92 percent / NaI / acetone / 3 h / Heating |
Multi-step reaction with 2 steps 1: borane-dimethyl sulfide complex / tetrahydrofuran / 0 - 20 °C 2: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 0 - 20 °C | ||
With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 0 - 20℃; for 2h; | ||
With indium(III) bromide; 1,1,3,3-Tetramethyldisiloxane; iodine In chloroform at 60℃; Inert atmosphere; | ||
Multi-step reaction with 2 steps 1.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 0 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triphenylphosphine; iodine; 1H-imidazole / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere; Darkness |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With sodium tetrahydroborate; [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate; oxygen; caesium carbonate In dichloromethane at 40℃; for 40h; Irradiation; | |
Multi-step reaction with 3 steps 1: SOCl2 2: H2O2, aq. NaOH 3: acetone |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide In water for 18h; Heating / reflux; | 4.A Example 4; Step A; Synthesis of 2-{2-[4-(trifluoromethoxy)phenylthio]phenyl}acetic acid as an intermediate A mixture of 26.2 grams (0.47 mole) of potassium hydroxide and 1.1 grams (0.018 mole) of powdered copper (catalyst) in 200 mL of water was stirred, and 30.6 grams (0.117 mole) of 2-iodophenylacetic acid and 22.7 grams (0.117 mole) of 4-trifluoromethoxyphenol were added. Upon completion of addition the reaction mixture was warmed to reflux where it stirred for about 18 hours. After this time the reaction mixture was cooled to ambient temperature and filtered. The filtrate was poured into500 mL of aqueous 10% hydrochloric acid and the mixture was extracted with three 250 mL portions of ethyl acetate. The combined extracts washed with an aqueous solution saturated with sodium chloride, dried with sodium sulfate, filtered, and concentrated under reduced pressure, yielding 39.6 grams of the subject compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With potassium hydroxide;copper; In water;Heating / reflux; | [2-(2-Methoxy-phenylsulfanyl) -phenyl]-acetic Acid 2-Methoxythiophenol (2.8 g, 20 mmol) was added to a solution of potassium hydroxide (4.6 g, 80 mmol) in water (50 ml) and the mixture was degassed for 15 minutes. 2-Iodophenylacetic acid (5.24 g, 20 mmol) and copper bronze (64 mg, 1 mmol) were then added to the reaction mixture, which was refluxed overnight. The solution was cooled down, filtered and the precipitate washed with water (50 ml). The filtrate was acidified with conc HCl (pH 1), extracted with dichloromethane (3*100 ml). The organics were combined, extracted with saturated brine, dried over sodium sulphate and evaporated in vacuo to give the title compound as a pale brown oil which solidified overnight. The compound was used without any further purification (5.10 g, 93%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In methanol | 264.1 2-(2-Benzotriazol-1-yl-phenyl)-1-[4-(6-ethyl-thieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-ethanone Step 1: 2-Iodophenylacetic acid (1.45 g) was added to a mixture of methanol (100 mL) and acetyl chloride (5 mL). After stirring at room temperature for 3 hours, the solvent was removed and the residue was dried under vacuum giving the desired 2-iodophenylacetic acid methyl ester. Yield=100% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; acetic acid; diisopropylamine In tetrahydrofuran; ethyl acetate | 138.1 Step 1 Step 1 2-(2-iodophenyl)butanoic acid To a solution of diisopropylamine (5.6 mL, 40 mmol) in dry THF (60 mL) at -10° C. was added 1.6M BuLi (25 mL, 40 mmol). After 30 min, a solution of 2-iodophenylacetic acid (5.24 g, 20 mmol) in THF (20 mL) was slowly added. The solution was stirred for 1 h, at which point iodoethane (1.6 mL, 117 mmol) was added. After 2 h at r.t. the reaction was quenched with 0.5M NH4 OAc solution and 6M HCl (10mL) and the product was extracted with EtOAc. The organic layer was dried (MgSO4) and evaporated to give an oily residue which was purified by flash chromatography (15:85 EtOAc:hexane containing 5% AcOH) to give 4.37 g of the title compound as an off-white solid. | |
With n-butyllithium; acetic acid; diisopropylamine In tetrahydrofuran; ethyl acetate | 138.1 2-(2-iodophenyl)butanoic acid Step 1 2-(2-iodophenyl)butanoic acid To a solution of diisopropylamine (5.6 mL, 40 mmol) in dry THF (60 mL) at -10° C. was added 1.6M BuLi (25 mL, 40 mmol). After 30 min, a solution of 2-iodophenylacetic acid (5.24 g, 20 mmol) in THF (20 mL) was slowly added. The solution was stirred for 1 h, at which point iodoethane (1.6 mL, 117 mmol) was added. After 2 h at r.t. the reaction was quenched with 0.5M NH4 OAc solution and 6M HCl (10 mL) and the product was extracted with EtOAc. The organic layer was dried (MgSO4) and evaporated to give an oily residue which was purified by flash chromatography (15:85 EtOAc:hexane containing 5% AcOH) to give 4.37 g of the title compound as an off-white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide for 2h; | 102 To a stirred solution of 2-iodophenyl acetic acid (1 g, 3.81 mmol) in DMF (20 mL) was added K2CO3 (1.5 g) followed by MeI (475 μl). The resulting suspension was stirred for 2 h at which time the reaction was poured into water. This mixture was extracted with ether (20 mL×3) followed by washing of combined ether layers with sat. aq. NaHCO3, then sat. aq. NaCl. The organic phase was dried over Na2SO4, concentrated under reduced pressure to yield pure (2-iodo-phenyl)acetic acid methyl ester which was used for next reaction without any further purification |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydrogenchloride; sodium chloride; sodium carbonate In thionyl chloride; dichloromethane; water; benzene | 1 Preparation of N,N-dimethyl-o-iodophenylacetamide EXAMPLE 1 Preparation of N,N-dimethyl-o-iodophenylacetamide In 100 ml of thionyl chloride was dissolved 72.0 g (0.275 mole) of o-iodophenylacetic acid, the reaction was carried out at an inner temperature of 50° C. for 1 hour under agitation and the mixture was refluxed for 30 minutes under agitation. After completion of the reaction, the unreacted thionyl chloride was removed by distillation under reduced pressure. Then, 30 ml of anhydrous benzene was added to the residue, and the solvent was removed by distillation under reduced pressure at an inner temperature of 40° C. Then, the residue was dissolved in 200 ml of anhydrous dichloromethane and the solution was added dropwise to 54.5 ml of a 50% aqueous solution of dimethyl amine under agitation at an inner temperature of 5° to 10° C. over a period of 20 minutes. Then, the reaction mixture was agitated for 1 hour at room temperature to complete the reaction. Then, 400 ml of water was added to the liquid reaction mixture, and the mixture was violently agitated and allowed to stand still to cause phase separation. The organic layer was washed with 2 times with 100 ml each of a 10% aqueous solution of hydrochloric acid, a 10% aqueous solution of sodium carbonate and a saturated aqueous solution of sodium chloride, and then dried with anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was subjected to reduced pressure distillaton to obtain 75.5 g of a yellow oily product (solidified under cooling) having a boiling point of 140° to 142° C. under 0.6 mmHg. The yield was 95.0%. Elementary analysis values: Found: H=4.31%, C=41.42%, N=4.62%; Calculated: H=4.19%, C=41.54%, N=4.84%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22.8 g (90%) | With potassium hydroxide; copper In water | 15 7,8-Difluoro-10-(4 -methylpiperazino)-10,11-dihydrodibenzo(b,f)thiepine The above diol (13.2 g), followed by o-iodophenylacetic acid (23.7 g) and "molecular" copper (0.7 g), is added to a solution of potassium hydroxide (17.2 g) in water (180 ml). The resulting mixture is refluxed for 7 hours, filtered while hot and the filtrate cooled and acidified with dilute hydrochloric acid. Upon standing overnight at room temperature, the product which originally separated as an oil sets to crystals. It is filtered, washed with water and air-dried, yielding 22.8 g (90%) of 2-(3,4-difluorophenylthio)phenylacetic acid which is crystallized from hexane; m.p. 54°-57° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In methanol; diethyl ether; dichloromethane at 0℃; for 1h; | 23 Methyl(2-iodophenyl)acetate (23- 1). Trimethylsilyl diazomethane (15.3 ml, 30.6 mmol, 2.0 M in diethyl ether) was added dropwise to a stirred, cooled O0C solution of (2-iodophenyl)acetic acid (4.0 g, 15.3 mmol) and MeOH (10 ml) in CH2CI2 (50 ml) and the solution was stirred at 0 0C for 1 hour. The yellow solution was purged with nitrogen for 10 minutes. The solvent removed in vacuo and the residue was azeotroped with THF (3 x 25 ml) to afford 4.2 g, 100 % of 23-l as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With potassium hydroxide In water monomer Heating / reflux; | 93.1 Example 93: 2-Methyl-N-(2-phenylethyl)-10,11-dihydrodibenzo[b,f]thiepine-3- sulfonamide 5,5- dioxide.Step 1. {2-[(4-Methylphenyl)thio]phenyl}acetic acidCO2H[0338] A mixture of 4-methyl benzene thiol (12.85 g, 104 mmol), 2-iodo-phenyl acetic acid (24.7 g, 94.2 mmol), copper powder (1.01 g) and potassium hydroxide (26.1 g, 471 mmol) in water (600 ml_) was heated to reflux overnight. The reaction filtered to remove the copper salts and made acidic with concentrated HCI and diluted with water. The aqueous layer (1 L) was filtered to afford the desired product as a solid that was triturated with methanol to afford 13.36 g of white solid (55 %).[0339] MS (ESI) m/z 257;HRMS: calculated for Ci5Hi4O2S + H+, 259.07873; found (ESI, [M+Hf), 259.0786 |
With copper atom; potassium hydroxide In water monomer at 170℃; for 0.333333h; Microwave irradiation; | 1 Intermediate 1: 2-[2-(p-tolylsulfanyl)phenyl]acetic acid 500mg of 2-iodophenylacetic acid (1.9 mmol), 261 mg of p-thiocresol (2.10 mmol, 1.1 eq),18 mg of copper powder (0.29 mmol, 0.15 eq) and 535 mg of potassium hydroxide (9.54mmol, 5 eq) were mixed in 12 ml of water and heated in a microwave oven at 170°C for20 mn. The reaction mixture was acidified to pH = 2 with concentrated HCI and extractedthree times with 20 ml of dichloromethane. The organic phases were separated with anhydrophobic membrane, further washed with lOmI of iN HCI and concentrated todryness, yielding 473 mg of clear oil solidifying on standing and used as a crude in the next step.LCMS: mlz = 276 [M+NH4+], 534 [2M+NH4+] | |
Stage #1: para-thiocresol With potassium hydroxide In water monomer at 50℃; for 0.166667h; Stage #2: 2-(2-iodophenyl)acetic acid With copper atom In water monomer Reflux; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With toluene-4-sulfonic acid In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With toluene-4-sulfonic acid In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With dmap; diisopropyl-carbodiimide In dichloromethane at 0 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: o-iodophenylacetic acid With copper(l) iodide; potassium carbonate; sulfur In N,N-dimethyl-formamide at 90℃; for 12h; Inert atmosphere; Stage #2: With sodium tetrahydroborate In N,N-dimethyl-formamide at 40℃; Inert atmosphere; Cooling with ice; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With palladium diacetate; triethylamine; triphenylphosphine In acetonitrile at 90℃; for 18h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With copper atom; potassium hydroxide In water monomer for 19h; Reflux; | |
96% | Stage #1: thiophenol With potassium hydroxide In water monomer at 50℃; for 0.166667h; Stage #2: 2-(2-iodophenyl)acetic acid With copper atom In water monomer Reflux; Inert atmosphere; | |
Stage #1: 2-(2-iodophenyl)acetic acid; thiophenol With potassium hydroxide In water monomer for 5h; Heating / reflux; Stage #2: With hydrogenchloride In water monomer | Equimolar amounts of 2-iodophenylacetic acid (200 mg, 0.763 mmol, Aldrich) and Thiophenol (78 μl_, 0.763 mmol, Aldrich) in a solution of KOH (475 mg) in water (5 ml.) and copper bronze (5 mg, 0.0763 mmol, Aldrich) were refluxed for 5 hours. The reaction mixture was taken-up with EtOAc and it was washed with water, diluted HCI solution and brine. The aqueous phase was concentrated and filtered. 1 N HCI was added to the filtered solution and a precipitate was formed. The title compound was collected after filtration as a white solid (180 mg);MS (ESI) m/z: 267 [M+Na]+; 1H NMR (200 MHz, CDCI3): δ 3.88 (s, 2 H), 7.16 - 7.33 (m, 7 H), 7.41 - 7.45 (d, 2 H), 10.77 (s, 1 H). |
With copper atom; potassium hydroxide In water monomer at 50℃; for 24h; Reflux; | 4.2.28 Dibenzo[b,f]thiepin-10(11H)-one (38a) KOH (722mg, 12.9mmol, 3.3equiv.) was dissolved in 7.8mL of water, benzenethiol (35a) (0.40mL, 3.90mmol, 1.0equiv.) was added and the mixture was heated to 50°C. Copper powder (74mg, 1.17mmol, 0.3equiv.) and 2-(2-iodophenyl)acetic acid (36) (980mg, 3.74mmol, 0.96equiv.) was added. The reaction mixture was stirred at reflux for 24h, then cooled to room temperature. The yellow precipitate was filtered off, and the filtrate was acidified with HClaq. (1M). The aqueous phase was extracted with EtOAc (5×). The organic phases were united, washed with brine, dried over Na2SO4, filtered and the solvent was removed under reduced pressure. Thus were obtained 1.20g (100% plus impurities) of 2-(2-(phenylthio)phenyl)acetic acid (37a) as a yellow solid; the crude was used in the next step without further purification. (0098) 4g of oily P2O5 was heated to 150°C under stirring. The crude 2-(2-(phenylthio)phenyl)acetic acid (37a) was added in little portions and the mixture was stirred at 150°C for 4h, then cooled to room temperature. Ice and water were carefully added, and the resulting aqueous solution was extracted with EtOAc (5×). The organic phases were united, washed with brine, dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The crude residue was purified by flash chromatography (eluent Hexane/EtOAc=97/3 to 9/1), yielding 403mg (46%) of dibenzo[b,f]thiepin-10(11H)-one (38a) as a green-yellow solid. (0099) Rf (Hexane/EtOAc=8/2)=0.15; 1H NMR (400MHz, CDCl3) δ (ppm)=8.20 (1H, dd, H-13, J=8.0Hz, J=1.7Hz), 7.65 (1H, dd, H-7, J=7.7Hz, J=1.2Hz), 7.61 (1H, dd, H-11, J=7.8Hz, J=1.1Hz), 7.28-7.49 (4H, m, H-10, H-6, H-12 and H-4), 7.20 (1H, dt, H-5, J=7.6Hz, J=1.4Hz), 4.38 (2H, s, H-2); 13C NMR (101MHz, CDCl3) δ (ppm)=191.5 (C-1), 140.4 (C-3), 137.8 (C-8), 136.3 (C-9), 134.7 (C-14), 132.6 (C-11), 131.7 (C-6), 131.4 (C-4), 131.0 (C-13), 130.1 (C-5), 129.6 (C-7), 127.3 (C-12), 127.3 (C-10), 51.2 (C-2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 4-Fluorothiophenol; 2-(2-iodophenyl)acetic acid With potassium hydroxide In water monomer Heating / reflux; Stage #2: With hydrogenchloride In water monomer | A solution of KOH (86 mg, 1.53 mmol) in water (7 mL) was reacted under N2 atmosphere with 4-Fluorothiophenol (41 μl_, 0.382 mmol, Aldrich) and the reaction mixture was stirred at 500C for 15 min. Then 2-iodophenylacetic acid (100 mg, 0.382 mmol, Fluka) and copper bronze (0.24 mg, 0.004 mmol, Aldrich) were added and the reaction mixture was heated at reflux overnight. The hot mixture was filtered through a fritted filter funnel and the filtrate was quenched with 1 N HCI and extracted with diethyl ether. Evaporation of the solvent gave the title compound (50 mg);MS (ESI) m/z: 285 [IvHNa]+; IR (CHCI3): 3066, 1713 cm"1; 1H NMR (200 MHz, CDCI3): δ 3.87 (s, 2 H), 6.91 - 7.00 (m, 2 H), 7.18 - 7.36 (m, 5 H), 7.85 (d, 1 H), 10.22 (s, 1 H). | |
Stage #1: 4-Fluorothiophenol With potassium hydroxide In water monomer at 50℃; for 0.166667h; Stage #2: 2-(2-iodophenyl)acetic acid With copper atom In water monomer Reflux; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With copper(l) iodide; 8-quinolinol; potassium hydroxide In water; dimethyl sulfoxide; <i>tert</i>-butyl alcohol at 100℃; for 48h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | In methanol at 20 - 50℃; Inert atmosphere; Microwave irradiation; Combinatorial reaction / High throughput screening (HTS); | 16 General procedure for the Ugi four-component reaction. General procedure: In a 100 mL round bottom flask the corresponding amine (1 mol) (only when amine hydrochloride was used, 1 mmol of Et3Nwas added), the 2-benzoylacetaldehyde (1 mol), the corresponding carboxylic acid (1 mol) and the tert-butyl isocyanide (1 mol) were dissolved in 3 ml of MeOH and stirred at room temperature. Then the flask was connected to a condenser and placed into the microwave cavity under an argon atmosphere and the reaction mixture was irradiated with 50 W for 10 min at 50 °C and then allowed to cool to room temperature. The reaction solvent was evaporated and the crude product was purified by silica gel flash column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 18h; | General procedure: A mixture 2-amino-4,5-dimethylthiophene-3-carboxamide (340 mg, 2 mmol), 2-(1-naphthalen-1-yl)acetic acid (372 mg, 2 mol), EDC (458 mg, 2.4 mmol), HOBt (324 mg, 2.4 mmol), DIEA ( 1.1 mL, 6 mmol) in DMF (10 mL) was stirred at room temperature for 18 h. The reaction mixture was poured into 100 mL of water then extracted with ethyl acetate (150 mL). The organic layer was washed with saturated NaHCO3 solution (3 x 50 mL), brine (3 x 50 mL), water (3 x 50 mL) respectively. The ethyl acetate layer was dried over MgSO4 and concentrated. The residue was chromatographed over silica gel (30 to 40% ethyl acetate in haxane) to afford compound 1 (277 mg, 41%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With triethylamine In 1,4-dioxane at 60℃; for 2h; Inert atmosphere; Sealed tube; | 34 [2-(1H-Pyrrolo[2,3-b]pyridin-4-ylethynyl)-phenyl]-acetic acid Example 34 [2-(1H-Pyrrolo[2,3-b]pyridin-4-ylethynyl)-phenyl]-acetic acid Dichloro bis(triphenylphosphine) palladium (II) (17 mg, 0.024 mmol), and triethylamine (335 μL, 241 mg, 2.39 mmol) were added to a solution of intermediate 10.2 (102 mg, 1.06 mmol) and (2-iodophenyl)acetic acid (125 mg, 0.48 mmol) in 1,4-dioxane (2 mL), and placed in a sealable tube. Nitrogen gas was bubbled in the reaction mixture for 5 min, before the tube was sealed and the reaction mixture was heated at 60° C. for 2 h. After cooling to room temperature, the brown solution was filtered through Celite and concentrated under vacuo. The residue was then dissolved in a solution 5 N of sodium hydroxide, washed with ethyl acetate (3*20 mL), neutralized with a solution 5 N of hydrochloric acid, and filtered to afford the title compound (60 mg, 45%) as a beige solid (HPLC: 99%, RT: 6.19 min) 1H NMR (DMSO-d6) δ=8.25 (d, J=4.8 Hz, 1H), 7.66 (d, J=7.3 Hz, 1H), 7.62 (dd, J=3.3, 2.6 Hz, 1H), 7.45-735 (m, 3H), 7.21 (d, J=5.1 Hz, 1H), 6.66 (dd, J=3.5, 1.8 Hz, 1H), 3.90 (s, 2H); MS (m/z) 277 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃; for 15h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
235 mg | With copper(l) iodide; caesium carbonate In N,N-dimethyl-formamide at 20 - 110℃; | 186.1 (2-[1,2,3]Triazol-2-ylphenyl)acetic acid To a solution of 2-iodophenylacetic acid (500mg) in DMF (5ml) was added 1H-1,2,3-triazole (0.214 mL), followed by Cs2CO3(1.21 g) upon which the temperature increased. The reaction mixture was cooled to RT and copper iodide (17.6mg) was added. The mixture was stirred at RT overnight and at 110°C for 1h 30. After cooling down, H2O/EA was added and the phases were separated. The aq. phase was acidified to pH=1 with 1 M HCl and extracted with EA. The combined org. phases were dried (Na2S04) and evaporated in vacuo. The residue was purified by CC (Biotage, SNAP 25g cartridge, solvent A: Hept; solvent B: EA/AcOH 100/1 ; gradient in %B: 18 for 4CV, 18 to 100 over 10CV, 100 for 2CV) to afford 235 mg of white solid. LC-MS (B): tR = 0.60min; [M+H]+: 204.42. |
235 mg | With copper(l) iodide; caesium carbonate In N,N-dimethyl-formamide at 20 - 110℃; | 186.1 186.1. (2-[1,2,3]Triazol-2-yl-phenyl)-acetic acid To a solution of 2-iodophenylacetic acid (500 mg) in DMF (5 mL) was added 1H-1,2,3-triazole (0.214 mL), followed by Cs2CO3 (1.21 g) upon which the temperature increased. The reaction mixture was cooled to RT and copper iodide (17.6 mg) was added. The mixture was stirred at RT overnight and at 110° C. for 1 h30. After cooling down, H2O/EA was added and the phases were separated. The aq. phase was acidified to pH=1 with 1M HCl and extracted with EA. The combined org. phases were dried (Na2SO4) and evaporated in vacuo. The residue was purified by CC (Biotage, SNAP 25 g cartridge, solvent A: Hept; solvent B: EA/AcOH 100/1; gradient in % B: 18 for 4CV, 18 to 100 over 10CV, 100 for 2CV) to afford 235 mg of white solid. LC-MS (B): tR=0.60 min; [M+H]+: 204.42. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | Stage #1: o-iodophenylacetic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h; Stage #2: diisopropylamine In dichloromethane at 0 - 20℃; | I1.1 Step 1: (N,N)-Diisopropyl 2-iodophenylacetamide Step 1: (N,N)-Diisopropyl 2-iodophenylacetamide To a solution of 2-iodophenylacetic acid (11.0 g, 42.0 mmol, commercially available) in dichloromethane (85 mL) was added oxalyl chloride (7.11 mL, 84 mmol) followed by 2 drops of dimethyl formamide. The solution as stirred at room temperature for 2 h and the solvents were removed in vacuo. The residue was taken up in dichloromethane (100 mL) and cooled at 0° C. Diisopropylamine (17.6 mL, 126 mmol) was then added and the solution as warmed to room temperature. The solvents were removed in vacuum. The residue was partitioned between ethyl acetate and water and extracted with ethyl acetate. The combined organic layers were washed with hydrogen chloride (1N), brine, dried and concentrated to give 14.3 g of (N,N)-Diisopropyl 2-iodophenylacetamide (White solid, 99%). C14H20INO, MW: 345.23; LCMS (method A) RT 1.90 min; Mass 346 (100%, MH+), 268 (10%, MNa+); IR: 2965, 1634, 1438, 1369, 1337 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.84 (d, 1H), 7.22-7.35 (m, 3H), 6.84-6.97 (m, 1H), 3.91 (m, 1H), 3.76 (s, 2H), 3.43 (m, 1H), 1.46 (d, 3H), 1.15 (d, 6H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With dmap; triethylamine; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 4h; Inert atmosphere; Reflux; | |
With triethylamine; 1,1'-carbonyldiimidazole In dichloromethane at 0 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: o-iodophenylacetic acid With lithium diisopropyl amide In tetrahydrofuran; n-heptane; ethylbenzene at 0℃; for 0.666667h; Inert atmosphere; Stage #2: ethyl iodide In tetrahydrofuran; n-heptane; ethylbenzene at 20℃; for 4h; | 1.a Key Intermediate 1: 2-(2-Ethynylphenyl)butanamide (KI) Key Intermediate 1: 2-(2-Ethynylphenyl)butanamide (KI)(a) 2-(2-Iodophenyl)butanoic acid (Ii)Lithium diisopropylamide solution (2.0 M in THF/heptane/ethylbenzene, 3.82 mL, 7.63 mmol) was added to dry THF (10 mL) under an atmosphere of nitrogen and cooled to 0 00. A solution of 2-(2-iodophenyl)acetic acid (500 mg, 1.91 mmol) in dryTHF (15 mL) was then added dropwise. This solution was stirred for 40 minutes at 000 before the addition of iodoethane (0.92 mL, 11 mmol). The solution was returnedto room temperature and stirred for 4 hours. The resulting mixture was quenched with the addition of H20 (10 mL) and then 2 M HCI (20 mL). The aqueous layer was extracted with EtOAc (3 x 30 mL), the organic layers were combined and washedwith brine, dried over Mg504 and the solvent was evaporated under reducedpressure. The residue was adsorbed onto silica gel and purified using columnchromatography (Biotage Isolera, 5i02 cartridge, 0-40% EtOAc in petroleum benzine40-60 00) to give the title compound Ii as a pale yellow oil (479 mg, 87%); 1H NMR(400 MHz, d6-DMSO) O 12.49 (5, 1H), 7.88 (dd, J= 7.9, 1.2 Hz, 1H), 7.39 (td, J= 7.6,1.2 Hz, 1H), 7.32 (dd, J= 7.8, 1.7 Hz, 1H), 7.01 (Jm, 1H), 3.77 (t, J= 7.5 Hz, 1H),1.98-1.86 (m, 1H), 1.73-1.60 (m, 1H), 0.85 (t, J= 7.3 Hz, 3H).JH2Ii 12 13 Ki |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With Davy's reagent methyl In chlorobenzene at 140℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: o-iodophenylacetic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0℃; for 0.0333333h; Inert atmosphere; Stage #2: 2-mercaptophenylethane In dichloromethane at 0 - 25℃; for 3.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bromine; phosphorus trichloride at 70 - 90℃; for 19.5h; | General procedure for the synthesis of α-bromoamides General procedure: In air, a two neck oven dried round bottom flask equipped with a reflux condenser capped with a calcium chloride drying tube was charged with the substituted phenyl acetic acid (1.0equiv) and phosphorous trichloride (1.0equiv). Bromine (2.0equiv) was added via syringe and the reaction mixture was heated for 1.5h at 70-90°C. After 1.5h, excess bromine (0.4-0.6equiv) was added and reaction was stirred for another 18h at 70-90°C. The mixture was cooled to room temperature and poured into 150mL of ice water. The mixture was extracted using toluene (2×150mL), dried over anhydrous Na2SO4, and the residual bromine and toluene were removed under reduced pressure. The crude bromo(phenyl)acetyl chloride was used directly for the next step |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With silver(I) acetate; palladium diacetate; toluene-4-sulfonic acid; acetic acid In water at 70℃; for 48h; Sealed tube; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With iron(III) chloride; oxygen In N,N-dimethyl-formamide at 100℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With norborn-2-ene; palladium diacetate; caesium carbonate; triphenylphosphine In methanol at 90℃; Inert atmosphere; Sealed tube; | General Procedure General procedure: Pd(OAc)2 (22.4 mg, 0.10 mmol, 0.1 equiv), Ph3P (57.6 mg, 0.22, 0.22 equiv), and Cs2CO3 (1.63 g, 5 mmol, 5 equiv) were added to a flamedried, sealable vial under argon. Dry, degassed MeCN or DMF (3 mL) was added and the yellow mixture was stirred under argon for approximately 5 min. Aryl iodide (1.00 mmol, 1 equiv), alkyl iodide (10.00 mmol, 10 equiv), and olefin (5.00 mmol, 5 equiv) were added successively to the reaction mixture under argon. The mixture was stirred for 5 min, then solid norbornene (470 mg, 5.00 mmol, 5 equiv) was added. After a final argon purge, the vial was capped and placed in an oil bath that had been preheated to 90 °C. After 4-10 h, the mixture was cooled to r.t. Reactions performed in MeCN were filtered over a short pad of Celite (eluting with CH2Cl2) and concentrated in vacuo. Reactions performed in DMF were diluted with EtOAc- hexanes (1:1) and washed with brine twice. After drying with MgSO4, the organic layer was filtered and concentrated. The crude products were purified by flash column chromatography (CH2Cl2-hexanes, 1:5, then Et2O-hexanes, 1:100→1:25). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: o-iodophenylacetic acid; 3,5-dimethoxyphenylboronic acid With lithium hydroxide In tetrahydrofuran; water at 20℃; for 0.116667h; Inert atmosphere; Stage #2: With tris-(dibenzylideneacetone)dipalladium(0) In tetrahydrofuran; water at 80℃; for 14h; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide In acetic acid butyl ester at 20℃; for 2h; Reflux; | 3 17.3 Ethyl [3-(2-iodobenzyl)imidazo[1,5-a]pyridin-1-yl]acetate (77) Aminoester 76 (0.92 g, 4.50 mmol) and 2-(2-iodophenyl)acetic acid (1.36 g, 5.2 mmol) were dissolved in 23 ml butyl acetate. 1-Propanephosphonic anhydride solution (T3P, 7 ml, 11.7 mmol) was added and the mixture was stirred for 1 h at room termpature and then 1 h at reflux. The mixture was allowed to cool to room temperature and was washed twice with 4% sodium bicarbonate solution. The organics were dried over anhydrous sodium sulphate, filtrered and evaporated under reduced pressure. The residue was purified using the SP-1 purification system (ethyl acetate-hexane gradient, 0:100 rising to 30:70) to give 77 (1.1 g, 2.62 mmol, 58% yield) as a pale yellow solid. Purity 100%. 1H NMR spectrum not recorded. UPLC/MS (3 min) retention time 1.76 min. LRMS: m/z 421 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: o-iodophenylacetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.25h; Stage #2: 2-methyl-8-morpholinoimidazo[1,2-a]pyrazin-3-amine With triethylamine In dichloromethane at 25℃; for 8h; | General procedure A for the the reactions in Table 1 leading to products 1 and 14a-14k General procedure: A 50 mL, round-bottom flask equipped with a magnetic stir bar was charged with carboxylic acid (2 equiv), HOBT (2 equiv) and EDCI (2 equiv). The reagents were dissolved in DCM and the solution was allowed to stir for 15 min. Subsequently, different amino compounds (11-13) (1 equiv) and TEA (5 equiv) were added to the reaction vessel and the solution was allowed to react at 25 °C for 8 h. Upon completion, the solvent was removed under reduced pressure and the residue was purified by flash chromatography (SiO2, DCM: MeOH = 20:1) to afford corresponding compounds 14a-14k. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With gallium(III) trichloride; Hexamethyldisiloxane; copper dichloride In 1,2-dichloro-ethane at 40℃; for 3h; Sealed tube; Inert atmosphere; | |
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 1 h / 10 °C / Inert atmosphere 2: triphenylphosphine; tetrachloromethane / dichloromethane / 5 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 5 h / 0 °C 2: triphenylphosphine; tetrachloromethane / dichloromethane / 5 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With silver triflate-bis(1,10-phenanthroline) complex; dibromoisocyanuric acid In 1,2-dichloro-ethane at 20℃; for 12h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With dmap; dicyclohexyl-carbodiimide In dichloromethane | 65.4 Step 4: 2-((2-(allyloxy)phenyl)amino)-2-oxoethyl 2-(2-iodophenyl)acetate 2(2-iodophenyl-)acetic acid (35.8 mg, 0.137 mmol) was dissolved in DCM (4 mL), and added DCC (29.1 mg, 0.141 mmol) and a catalytic amount of DMAP followed by the alcohol from step 3 (30.1 mg, 0.145 mmol). The mixture was left stirring overnight. The suspension was filtered over cotton to remove the bulk of DCU and purified by column chromatography (40% to 75% EtOAc in PE) to yield 60.3 mg of the title compound (98%). TLC: Rf (5% MeOH in DCM): 0.70 1H NMR (400 MHz, DMSO-d6) δ: 9.22 (bs, 1 H), 7.94 (bd, J = 7.9 Hz, 1 H), 7.87 (ddd, J = 7.9, 1.2, 0.4 Hz, 1H), 7.44 (ddd, J = 7.5, 1.9, 0.4 Hz, 1H), 7.39 (dt, J = 7.3, 1.3 Hz, 1H), 7.01-7.12 (m, 3H), 6.92 (ddd, J = 7.9, 6.4, 2.4 Hz, 1 H), 6.08 (ddt, J = 17.3, 10.6, 5.2 Hz, 1 H), 5.44 (dq, J = 17.4, 1.8 Hz, 1 H), 5.28 (dq, J = 10.6, 1.6 Hz, 1H), 4.78 (s, 2H), 4.65 (dt, J = 5.1, 1.6 Hz, 2H), 3.95 (s, 2H) ppm 13C NMR (101 MHz, DMSO-d6) δ: 169.6, 166.2, 148.4, 138.9, 137.5, 133.5, 131.2, 129.2, 128.4, 126.7, 124.7, 121.8, 120.5, 117.6, 112.7, 101.6, 68.9, 63.1, 45.0 ppm HRMS (ESI) m/z: (M+Na)+ calcd for C19H18INNaO4: 474.0173; found: 474.0176 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With 1,1'-bis-(diphenylphosphino)ferrocene; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; caesium carbonate; cesium fluoride In N,N-dimethyl-formamide at 80℃; for 24h; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; potassium hydroxide In water at 100℃; for 24h; Sealed tube; | 1 Intermediate 9: 2-[2-(4-isopropylphenyl)sulfanylphenyl]acetic acid 500 mg of 2-iodophenylacetic acid (1.91 mmol), 320 mg of 4-isopropylbenzenethiol (2.10 mmol, 1.1 eq), 109 mg of copper iodide (0.57 mmol, 0.30 eq) and 535 mg of potassium hydroxide (9.54 mmol, 5 eq) were mixed in 3 ml of water and stirred for 24h at 100CC in asealed vial. 12.1 mg of copper powder (0.19 mmol, 0.1 eq) was added and the reaction mixture was stirred at 100°C for 3h in a sealed vial. The reaction mixture was filtered. The mother liquors were acidified to pH = 2 with concentrated HCI and extracted three times with 20 ml of dichloromethane. The organic phases were separated with an hydrophobic membrane, further washed with 20m1 of 1 N HCI and concentrated to dryness, yielding 453mg of orange solid and used as a crude in the next step.LCMS: m/z = 304 [M+NH4+], 590 [2M+NH4+] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper; potassium hydroxide In water at 100℃; for 3h; Sealed tube; | 1 Intermediate 22: 2-[2-(4-ethylphenyl)sulfanylphenyl]acetic acid 500 mg of 2-iodophenylacetic acid (1.91 mmol), 290 mg of 4-ethylthiophenol (2.10 mmol,1.1 eq), 36 mg of copper powder (0.57 mmol, 0.30 eq) and 535 mg of potassium hydroxide (9.54 mmol, 5 eq) were mixed in 3 ml of water and stirred for 3h at 10000 insealed vial. 36 mg of copper iodide (0.19 mmol, 0.1 eq) was added and the reaction mixture was stirred at 100°C for 16h in a sealed vial. 36 mg of copper iodide (0.19 mmol, 0.1 eq) was added again and the reaction mixture was stirred at 100°C for 7h in a sealedvial. The reaction mixture was filtered. The mother liquors were acidified to pH = 2 with concentrated HCI and extracted three times with 20 ml of dichloromethane. The organic phases were separated with an hydrophobic membrane, further washed with 20m1 of 1HCI and concentrated to dryness, yielding 430 mg of yellow solid and used as a crudethe next step.LCMS: m/z = 290 [M+NH4+], 567 [2M+Na+] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With silver hexafluoroantimonate; chloro[di(1-adamantyl)-2-dimethylaminophenylphosphine]gold(I) In methanol at 0 - 80℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With silver hexafluoroantimonate; chloro[di(1-adamantyl)-2-dimethylaminophenylphosphine]gold(I) In methanol at 0 - 80℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With deuterium sodium hypophosphite monohydrate; α,α'-azodiizobutyramidine-dihydrochloride; sodium hydrogencarbonate In water at 80℃; for 12h; | 19 Example 5: Synthesis of Compound 2e General procedure: The iodo compound 1e (124mg),Sodium bicarbonate (NaHCO3, 105.0mg, 2.5equiv),Weigh in a 10mL reaction flask,Then add solvent water (H2O, 2.0ml),After dissolution, add deuterated sodium hypophosphite monohydrate (NaD2PO2·H2O, 216.0mg, 4.0equiv),The initiator azobisisobutylamidine dihydrochloride (AIBA, 40.6mg, 0.3equiv) reacts at 80 degrees Celsius,After the iodine compound 1e is consumed, the reaction is terminated (5h),Acidify the reaction system with dilute hydrochloric acid to pH 2-3, extract 3 times with ethyl acetate, combine the organic phases, wash with saturated brine, wash with saturated sodium thiosulfate solution, dry with anhydrous sodium sulfate, concentrate to obtain the crude product, and separate by column chromatography. The compound 2e (57.8 mg) was purified with a yield of 94% and a deuteration rate of 97%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dimethylsulfoxide-d6 at 20℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With copper (I) iodide; copper atom; potassium carbonate In N,N-dimethyl-formamide at 130℃; for 12h; Inert atmosphere; |
Tags: 18698-96-9 synthesis path| 18698-96-9 SDS| 18698-96-9 COA| 18698-96-9 purity| 18698-96-9 application| 18698-96-9 NMR| 18698-96-9 COA| 18698-96-9 structure
[ 1643-29-4 ]
3-(4-Iodophenyl)propanoic acid
Similarity: 0.88
[ 96606-95-0 ]
3-(2-Iodophenyl)propanoic acid
Similarity: 0.80
[ 1643-29-4 ]
3-(4-Iodophenyl)propanoic acid
Similarity: 0.88
[ 96606-95-0 ]
3-(2-Iodophenyl)propanoic acid
Similarity: 0.80
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
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.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :