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CAS No. : | 151169-74-3 |
Formula : | C6H5BCl2O2 |
M.W : | 190.82 |
SMILES Code : | OB(C1=CC=CC(Cl)=C1Cl)O |
MDL No. : | MFCD01075703 |
InChI Key : | TYIKXPOMOYDGCS-UHFFFAOYSA-N |
Pubchem ID : | 2734661 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
36% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 90℃; for 48h; | To a stirred solution of 4-BROMO-3-METHYL- pyridine N-oxide (0.985 G, 5.2 mmol) (prepared from 4-bromo-3-methyl-pyridine in the same manner as in Example 1B) and 2,3-dichloro PHENYLBORONIC acid (1-. 0 G, 5.2 mmol) in DME (5.8 mL) was added potassium carbonate (0.869 g, 6.3 mmol). The mixture was de- gassed by bubbling nitrogen with a syringe for 5 min through the mixture, followed by addition of Pd- (PPH3) 4 (0.606 g, 0.52 mmol). A reflux condenser was attached to the flask and the mixture heated to 90C for 48 h. The mixture was cooled to ambient temper- ature and partitioned between ethyl acetate and brine. The organic layer was washed with brine (3X20 ML) and dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting oil was purified by flash chromatography on silica gel elut- ing with 4% 7 N methanolic ammonia/DCM to provide the title compound (0.483 g, 5.24 mmol, 36% yield) as a white SOLID. 1H NMR (CDC13, 400 MHz) 5-8. 18 (s, 1H), 8. 14 (m, 1H), 7.57 (m, 1H), 7.33 (t, J=8 Hz, 1H), 7.15 (m, 1H), 7. 08 (d, J=6., 64 Hz, 1H, 2. 10 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30.5% | With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In toluene; at 85℃; for 18h; | To a stirred solution of 7A (0.800 g, 2.55 mmol) in 10 mL toluene was added 2, 3-dichlorophenyl boronic acid (0.975 g, 5.11 mmol) and cesium car- bonate (1. 33 g, 5.62 mmol). The mixture was de- gassed with nitrogen for 10 MIN, THEN E>D (PPh3) 4 (0. 148 g, 0. 128 mmol) was added. The mixture was heated to 85C for 18 h then cooled to ambient tem- perature. The crude product was partitioned between toluene and brine. The organic layer was washed (2 X 30 ML) with brine and concentrated in vacuo. The resulting oil was purified by flash chromatography on silica gel eluting with 2: 1 EtOAc/Hexane to pro- vide the title compound (0.295 g, 30. 5%) as a light oil which solidified upon standing to a white solid. 1H NMR (CDC13 400 MHz) 5 8.33 (d, J=2. 73 Hz, 1H), 8. 1 (d, J=1.56 Hz, 1H)., 7.51 (dd, J=1.95, 7.80 Hz, 1H), 7.27 (t, J=3.9 Hz, 1H), 7.23 (m, 2H), 4.2 (q, J=7. 02,14. 04 Hz, 2H), 3.71 (m, 2H), 2.91 (m, 2H), 2.49 (m, 1H), 2.05 (m, 2H), 1.9 (m, 2H), 1.28 (t, J=7.41 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 90℃; for 48h; | To a stirred solution of 2-bromo-5-methyl- pyridine (1.00 g, 5.81 mmol) and 2,3-dichloro phen- ylboronic acid (1.33 g, 6. 98 mmol) in DME (5.8 ML) was added potassium carbonate (1.21 g, 8.7 mmol). The mixture was degassed by bubbling nitrogen with a syringe for 5 min through the mixture, followed by addition of Pd (PPH3) 4 (0.672 g, 0.58 MMOL). A reflux condenser was attached to the flask and the mixture heated to 90C FOR 48 h. The mixture was cooled to ambient temperature and partitioned between. ethyl acetate and brine. The organic phase was washed with brine (3X20 mL) and dried over sodium sulfate, filtered, and concentrated IN VACUO. The resulting oil was purified by flash chromatography on silica gel ELUTING WITH 1 : 1 ethyl acetate: hexane to provide the title compound' (0. 380 g, 5. 81. MMOL, 27% yield) as A light yellow oil which ch solidified upon standing to an off with solid. 1H NMR (CDCl3, 400 MHz) 5 8. 54 (M, 1H), 7. 58 (m, 1H), 7.5 (s, 2H), 7.44 (DD, J=1.56, 7.42 Hz, 1H), 7.43 (m, 1H), 7. 27 (t, J=7.81 Hz, 1H), 2. 40 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In monoethylene glycol diethyl ether; water; at 80℃; for 17h; | Intermediate 2: 3-Bromo-6-(2,3-dichlorophenyl)pyridazine.To a suspension of 3,6-dibromopyridazine (5g, 21mmol) in ethylene glycol dimethyl ether (100ml) was added 2,3-dichlorophenyl boronic acid (4.03g, 21mmol), tetrakis(triphenylphosphine)palladium(0) (1.2g, 1.05mmol) and sodium carbonate (2N, aqueous) (50ml), the mixture was then heated to 800C for 17 hours whilst under argon. The dark crude reaction mixture was then evaporated to dryness. The residue was partitioned between water (200ml) and dichloromethane (300ml). The aqueous layer was separated and further extracted with dichloromethane (200ml). The combined dichloromethane layers were evaporated and the residue was purified by chromatography (90g of silica) eluting with 75% dichloromethane/ petroleum ether 40:60. The title compound was obtained as a pink coloured solid (680mg). 1H-NMR (CDCl3) ? 7.38 (IH, X, J= 8), 7.58-7.63 (2H, m), 7.70-7.76 (2H, m) LC/MS m/z [MH+] 305 consistent with molecular formula C10H581Br35Cl2N2 | |
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 17h; | To a suspension of 3,6-dibromopyridazine (5g, 21mmol) in ethylene glycol dimethyl ether (100ml) was added 2,3-dichlorophenyl boronic acid (4.03g, 21mmol), tetrakis(triphenylphosphine)palladium(0) (1.2g, 1.05mmol) and sodium carbonate (2N, aqueous) (50ml), the mixture was then heated to 800C for 17 hours whilst under argon. The dark crude <n="169"/>reaction mixture was then evaporated to dryness. The residue was partitioned between water (200ml) and dichloromethane (300ml). The aqueous layer was separated and further extracted with dichloromethane (200ml). The combined dichloromethane layers were evaporated and the residue was purified by chromatography (9Og of silica) eluting with 75% dichloromethane/ petroleum ether 40:60. The title compound was obtained as a pink coloured solid (680mg). 1H-NMR (CDCl3) δ 7.38 (IH, t, /= 8), 7.58-7.63 (2H, m), 7.70-7.76 (2H, m) LC/MS m/z [MH+] 305 consistent with molecular formula Ci0H581Br35Cl2N2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium fluoride; triphenylphosphonium tetrafluoroborate;tris(dibenzylideneacetone)dipalladium(0) chloroform complex; at 100℃; for 1h; | Intermediate 5: 3-Chloro-6-(2,3-dichlorophenyl)pyridazine.To a suspension of intermediate 4 (3.2g, 13.2mmol) in 1,4-dioxane (40ml) was added 2,3- dichlorophenyl boronic acid (2.5g, 13.2mmol), tris(dibenzylideneacetone)-di-palladium(0)- chloroform adduct (725mg, 0.79mmol), potassium fluoride (2.5g, 43.5mmol) and tri-tert- butylphosphine-tetra-fluoroborate (458mg, 1.58mmol), the mixture was then heated to 1000C for 1 hour whilst under argon. The dark crude reaction mixture was then evaporated to dryness. The solid was suspended in ethyl acetate (50ml) and poured through cellite and again evaporated to dryness. The sample was then purified by chromatography (9Og of silica) eluting with 10% ethyl acetate/ petroleum ether 40:60. The title compound was obtained as a white solid (2.2g). 1H-NMR (CDCl3) ? 7.38 (IH, t, J= 8), 7.59-7.63 (3H, m), 7.83 (IH, d, J= 9) LC/MS m/z [MH+] 259 consistent with molecular formula C10H535Cl3N2 | |
With potassium fluoride; tri-tert-butylphosphine-tetrafluoroborate;tris(dibenzylideneacetone)dipalladium(0) chloroform complex; In 1,4-dioxane; at 100℃; for 1h; | To a suspension of intermediate 4 (3.2g, 13.2mmol) in 1,4-dioxane (40ml) was added 2,3- dichlorophenyl boronic acid (2.5g, 13.2mmol), tris(dibenzyrideneacetone)-di-palladium(0)- chloroform adduct (725mg, 0.79mmol), potassium fluoride (2.5g, 43.5mmol) and tri-tert- butylphosphine-tetra-fluoroborate (458mg, 1.58mmol), the mixture was then heated to 1000C for 1 hour whilst under argon. The dark crude reaction mixture was then evaporated to dryness. The solid was suspended in ethyl acetate (50ml) and poured through cellite and again evaporated to dryness. The sample was then purified by chromatography (9Og of silica) eluting with 10% ethyl acetate/ petroleum ether 40:60. The title compound was obtained as a white solid (2.2g). 1H-NMR (CDCl3) δ 7.38 (IH, t, J= 8), 7.59-7.63 (3H, m), 7.83 (IH, d, J= 9) LC/MS m/z [MH+] 259 consistent with molecular formula Ci0H535Cl3N2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | With triethylamine;copper diacetate; In 1,2-dichloro-ethane; at 50℃; for 3h; | Step 1: N'-(2,3-Dichloro-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester A mixture of N-methyl-hydrazinecarboxylic acid tert-butyl ester (Intermediate 1; 1.00 g, 6.8 mmol), 2,3-dichlorophenylboronic acid (Lancaster; 1.29 g, 6.8 mmol), copper(II) acetate (1.24 g, 6.8 mmol) and triethylamine (960 μL, 6.8 mmol) in 1,2-dichloroethane (15 mL) was heated in an oil bath at 50 C. for 3 h. The mixture was allowed to cool, and it was then adsorbed onto silica gel and purified by chromatography using an ISCO 40 g column, eluding with 10% ethyl acetate/hexanes, to give N'-(2,3-dichloro-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (775 mg, 39%) as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In monoethylene glycol diethyl ether; water; at 80℃; for 16h; | Example 15: 4-[6-(2,3-Dichlorophenyl)-3-pyridazinyl]morpholine hydrochloride salt.To a suspension of intermediate 8 (500mg, 2.04mmol) in ethylene glycol dimethyl ether (10ml) was added 2,3-dichlorophenyl-boronic acid (428mg, 2.24mmol), tetrakis(triphenylphosphine)palladium(0) (120mg, 1 lOmu&;mol) and sodium carbonate (2N, aqueous) (5ml), the mixture was then heated to 800C for 16 hours whilst under argon. The dark crude reaction mixture was then evaporated to dryness. The residue was partitioned between water (200ml) and dichloromethane (300ml). The aqueous layer was separated and further extracted with dichloromethane (200ml). The combined dichloromethane layers were dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography (50g of silica) eluting with (30%) ethyl acetate/ petroleum ether 40:60 to give the free base of the title compound as an off white solid 1H- NMR (CDCl3.) ? 3.70-3.73 (4H, m), 3.87-3.89 (4H, m), 6.95 (IH, d, J= 9), 7.32 (IH, t, J= 8), 7.52- 7.54 (IH, m), 7.60-7.65 (2H, m). The sample was dissolved in 1,4-dioxane (5ml) and treated with hydrogen chloride (IM) solution in diethyl ether (ImI) which was then frozen and dried using freeze drying apparatus to obtain the title compound as an off white solid (160mg). LC retention time 2.47 mins, MS m/z 310 consistent with [MH+] for molecular formula C14H1335Cl2N3O | |
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 16h; | To a suspension of intermediate 47 (500mg, 2.04mmol) in ethylene glycol dimethyl ether (10ml) was added 2,3-dichlorophenyl-boronic acid (428mg, 2.24mmol), tetrakis(triphenylphosphine)palladium(0) (120mg, l lOμmol) and sodium carbonate (2N, aqueous) (5ml), the mixture was then heated to 800C for 16 hours whilst under argon. The dark crude reaction mixture was then evaporated to dryness. The residue was partitioned between water (200ml) and dichloromethane (300ml). The aqueous layer was separated and further extracted with dichloromethane (200ml). The combined dichloromethane layers were dried (Na2SC>4), filtered and evaporated. The residue was purified by chromatography (5Og of silica) eluting with (30%) ethyl acetate/ petroleum ether 40:60 to give the free base of the title compound as an off white solid 1H- NMR (CDCl3) δ 3.70-3.73 (4H, m), 3.87-3.89 (4H, m), 6.95 (IH, d, J = 9), 7.32 (IH, t, J = 8), 7.52- 7.54 (IH, m), 7.60-7.65 (2H, m). The sample was dissolved in 1,4-dioxane (5ml) and treated with hydrogen chloride (IM) solution in diethyl ether (ImI) which was then frozen and dried using freeze drying apparatus to obtain the title compound as an off white solid (160mg). LC retention time 2.47 mins, MS m/z 310 consistent with [MH+] for molecular formula C14H1335Cl2N3O |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 80℃; for 36h; | To a suspension of 3-bromopyridine-2,6-diamine (0.376 g, 2.00 mmol) in 1 ,4-dioxane (12 ml) and water (6 ml) was added 2,3-dichlorophenyl boronic acid (0.573 g, 3.00 mmol), potassium carbonate (0.552 g, 4.00 mmol) and palladium tetrakis(triphenylphosphine) (0.115 g, 0.01 mmol). The reaction was purged with nitrogen and heated at 809C for 18 hours. Further palladium tetrakis(triphenylphosphine) (0.115 g, 0.01 mmol) and 2,3-dichlorophenyl boronic acid (0.573 g, 3.00 mmol) were added and the reaction heated at 8O0C for a further 18 hours before concentrating in vacuo. The residue was taken up in ethyl acetate (20 ml) and washed with a saturated aqueous solution of K2CO3 before drying over MgSO4 and concentrating in vacuo. The residue was purified by silica gel column chromatography, eluting with 99:1 dichloromethane:methanol, then recrystallised from toluene to afford the title compound (0.180 g, 35% yield). <n="149"/>MP 170-1720C LCMS Rt=0.97 minMS m/z 254 [MH]+1HNMR (Cl6-DMSO): 5.00 (br s, 2H), 5.60 (br s, 2H), 5.75 (d, 1 H), 6.90 (d, 1 H), 7.23 (d, 1 H), 7.35 (t, 1 H), 7.55 (d, 1 H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | Example lb) (536mg, [2MMOL)] and Pd (PPh3) 4 (120mg, [0.] [LOMMOL)] in DME [(25ML)] were stirred at room temperature for [10MIN.] 2,3-Dichlorobenzene boronic acid [(L.] [OG,] 5.24mmol) was then added and the mixture heated to [80C] for 3h and for a further 18h at room temperature. The reaction was diluted with water [(50ML)] and ethyl acetate [(100ML),] the aqueous layer separated and washed with ethyl acetate [(50ML] x 2). The combined organics were washed with brine, dried [(MGS04)] and evaporated to give the title compound as a dark orange gum. The product was purified by flash chromatography (10% EtOAc/isohexane) to give a pale yellow solid (315mg, [62%).'H] NMR [(CDC13)] 8 2.56 (3H, s, CH3), 7.27- 7.33 (3H, [M,] ArH), 7.52 [(1H,] d, [ARH),] 7.90 [(1H,] d, ArH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | Tetrakis(triphenylphosphine)palladium(0) (14 mg, 0.012 mmol), was added to a solution of 2,3-dichlorophenylboronic acid (57 mg, 0.30 mmol) and 2-[(3-bromophenyl)-sulfonylamino]benzenesulfonamide (97 mg, 0.25 mmol) in DMF (1 mL). The reaction mixture was stirred at RT under argon for 15 minutes before addition of 2M Na2CO3 (0.5 mL). The reaction was stirred overnight at 90 C., filtered and purified by preparative HPLC (XTerra MS C8 column, acetonitrile/ammonium acetate buffer) to give the title compound (61 mg, 53%) as a white solid.1H NMR (400 MHz, Acetone-d6) δ ppm 7.97-8.01 (m, 2H), 7.80-7.89 (m, 1H), 7.60-7.74 (m, 4H), 7.47-7.52 (m, 2H), 7.42 (d, 1H), 7.15 (t, 1H). MS m/z M-H 455/457/459 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 100℃; for 0.666667h; | A mixture of 3-<;5-bromo-pyridin-3-yl)~propionic acid methyl ester (155mg). 2,3- dichlorobeϖzeneboronic acid {142 mg, 0.744 mmol), PdCI2(OpPf) CH2CI2 addυct (48.6 mg. 0.069 mmol) and Na2CO3 (2 M, 0.929 ml, 1.859 mmol) in DMF (5 ml) was heated at 1009C. After 40 min, solvent was removed in vacuo. The residue was purified via flash column (EtOAc/Heptane«0-20-25%, v/v) to give 3-[5-(2,3-Dichloro-phenyl)-pyridirv3-ylJ- propionic acid methyl ester (101 mg, 0.326 mmol, 43 % yield). ESl-MS mlr. 310[M+1f; 1H NMR (CDCI3, 400 MHz) δ 2.71 (t, J - 7.6 Hz, 2H), 3.05 (t, J * 7.6 Hz, 2H)1 3.70 (s, 3H), 7.23 (dd, J « 7.6, 1.8 Hz, 1H), 7.30 (t. J » 7.6 Hz, 1H)1 7.53 (dd, J * 7.6, 1.6 Hz, 1H), 7.63 (s, 1H). 8.52 (S. 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; N,N-dimethyl-formamide; at 100℃; for 1h;Inert atmosphere; | A mixture of 2,3-dichlorophenylboronic acid (279 mg, 1.464 mmol), methyl 2~(5- bromopyridin-3-yl)cyclopropanecarboxy»ate (357 mg, 1.394 mmol), PdCI2(dppf).CH?CI2 adduct (114 mg, 0.139 mmol) and Na2CO3 (2 M in water, 1.743 ml, 3.49 mmoi) in OMF (7 ml) was heated at 1OOCC under nitrogen atmosphere. After 1 h, the solvent was removed under vacuo. The residue was purified by flash column (EtOAc/Heptanes0- 25%, v/v) to give methyi 2-(5-(2,3-dichlorophenyl)pyridiϖ-3-yl)cyclopropanecarboxylate (335 mg, 1.040 mmol, 74 % yield). ESI-MS mlr. 322[M-H)*; 1H NMR (CDCI3, 400 MHz) 1.38-1.41 (m, 1H), 1.68-1.73 (m, 1H), 1.97-2.01 (m, 1H), 2.58-2.63 (m, 1H), 3.75 (s, 3H), 7.21 (dd, J = 7.6, 1.2 Hz, 1H), 7.30 (t, J * 7.6 Hz1 1H)1 7.43 (bs, 1H), 7.53 (, J * 7.6, 1.2 Hz, 1 H)1 848 (d, J = 1.6 Hz1 1 H), 8.50 (d, J * 1.6 Hz, 1 H), |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | With potassium carbonate;palladium bis[bis(diphenylphosphino)ferrocene] dichloride; In 1,4-dioxane; at 100℃; for 18h;Inert atmosphere; | To a solution of 2-Bromo-5-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yl)-1H-indole (80 mg, 0.28 mmol) and 2,3-Dichlorobenzeneboronic acid (53 mg, 0.28 mmol) in 1,4-dioxane (2 mL) was degassed and purged with nitrogen (10 min) and then aqueous K2CO3 (2 M, 0.2 mL) was added and purged with nitrogen again (20 min). Pd(dppf)2Cl2 (10 mol %, 21 mg) was added to the above reaction mixture and stirred at 100 C. After 18 h the reaction mixture was filtered through Celite and the filtrate extracted with EtOAc (3*20 mL). The organic phase (EtOAc layer) was washed with brine, dried over Na2SO4 and concentrated to a residue which was purified by column chromatography (10-30% EtOAc-Hexane) to obtain 2-(2,3-Dichloro-phenyl)-5-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yl)-1H-indole (25 mg, 26%), MS (M+H)=410. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 72℃;Inert atmosphere; | Synthesis of Compound 3155Ethyl 2-amino-7-(2,3-dichlorophenyl)-3H-l-benzazepine-4-carboxylate [000198] (2,3-Dichlorophenyl)boronic acid (764 mg, 4.00 mmol), ethyl 2-amino-7-bromo- 3H-l-benzazepine-4-carboxylate (399 mg, 1.29 mmol), toluene (15.0 mL), ethanol (1.5 mL), cesium carbonate (1.74 g, 5.34 mmol), and water (3.0 mL) were combined and the slurry was degassed with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (147 mg, 0.127 mmol) was added, the mixture degassed again, then heated in an oil bath at 72 C overnight. In the morning ethyl 2-amino-7-bromo-3H-l-benzazepine-4-carboxylate was consumed and the reaction was complete. The crude product was isolated using ethyl acetate and aq. NaHC03 washes. The crude product was dissolved in ethyl acetate and cooled to give a crop of crystals with sufficient purity. Final yield of desired product was 180 mg (37%). MS (ESI+) consistent forC19Hi6Cl2N202 (M+H)+: m/z 375.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With trans-bis(triphenylphosphine)palladium dichloride; sodium carbonate monohydrate; In 1,4-dioxane; water; at 60℃; for 1.5h; | General procedure: A mixture of 46-triflate (485mg, 1.22mmol), 2,4-dichlorophenylboronic acid (279mg, 1.46mmol), trans-dichlorobis(triphenyl-phosphine)palladium (ii) (85.0mg, 0.122mmol), and sodium carbonate monohydrate (453mg, 3.65mmol) in 1,4-dioxane/ H2O (1:1, 2.4ml) was stirred at 60C for 1.5h. The mixture was partitioned between H2O (10ml) and CH2Cl2 (15ml), the layers were separated, and the aqueous layer was extracted with CH2Cl2 (2×15ml). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The resulting brown oil was absorbed onto silica gel and purified by flash chromatography (silica gel, 20%-60% EtOAc/hexanes) to deliver ethyl 2-(2-aminopyrimidin-4-yl)-4-(2,4-dichlorophenyl)thiazole-5-carboxylate (259mg, 0.655mmol, 54% yield) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 90℃; for 16h;Sealed tube; | Pd2(dba)3 (3.3 mg, 3.6 imol) was added to a pre-degassed solution of 6-iodo-8-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-5(8H)-one (30.0mg, 0.O9Ommol), (2,3-dichlorophenyl)boronic acid (172 mg, 0.900 mmol), SPhos(3.0 mg, 7.2 imol) and potassium phosphate, tribasic (57.3 mg, 0.270 mmol) in toluene (1.0 mL) in a 4 mL vial. The vessel was sealed and the reaction mixture was heated to 90 C, with stirring. After 16 h, the reaction mixture was cooled and loaded directly onto a column andpurified by flash chromatography (0-100%, EtOAc incyclohexane) to give the title compound (20.8 mg, 66%) asa white solid. LCMS (Method A) : = 1.26 mi m/z = 352[M+H] . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 85℃; for 3h;Inert atmosphere; | 2-(4-(5-amino-6-chloro-l,2,4-triazin-3-yl)piperazin-l-yl)propan-l-ol (80 mg, 0.293 mmol), 2,3-dichlorophenyl)boronic acid (84 mg, 0.44 mmol), cesium carbonate (191 mg, 0.587 mmol) were dissolved in 2 mL degassed /?-dioxane/H,20 (v/v 3:1) and tetrakis(triphenylphosphine)palladium (85 mg, 0.073 mmol) was added under nitrogen atmosphere. The reaction mixture was stirred at 85C for 3 hours. Solids were filtered off and filtrate was concentrated under reduced pressure. The residue was subject to flash column chromatography to give a product as yellow solid (52 mg, 96.5% purity, 45.0% yield). LC- MS [ESI-MH+]: mlz 383; -NMR (500MHz, DMSO-d6) δ 0.945 (3H, d, J = 6.5 Hz), 2.550 (4H, m), 2.610 (1H, m), 3.702 (4H, br), 4.026 (IH, m), 4.340 (1H, dd, Ji = 4.5 Hz, J2 = 6.5 Hz). 6.450 - 7.100 (IH, br), 7.358 (IH, dd, Ji = 1.5 Hz, J2 = 8.0 Hz), 7.448 (IH, t, J = 2.5 Hz), 7.710 (lH, dd, Ji = 1.5 Hz, J2 = 8.0 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 85℃; for 3h;Inert atmosphere; | (5 -l-((5-Amino-6-chloro-l,2,4-triazin-3-yl)amino)-3- (2,2,2-trifluoroethoxy)propan-2-ol (67 mg, 0.222 mmol), (2,3-dichlorophenyl)boronic acid I (85 mg, 0.444 mmol), cesium carbonate (145 mg, 0.444 mmol) were dissolved in 2 mL degassed /^-dioxane/HsO (v/v 3:1) and tetrakis(triphenylphosphine)palladium (121 mg, 0.105 mmol) was added under nitrogen atmosphere. The reaction mixture was stirred at 85C for 3 hours. LC-MS analysis indicated the reaction was completed. Solids were filtered off and filtrate was concentrated under reduced pressure. The residue was subject to flash column chromatography to give a product as white solids (70 mg, 95.3%, 76% yield). LC-MS [ESI- MH+]: mlz 412; -NMR (500MHz, CDC13) δ 3.641 (IH, br), 3.709 (3H, m), 3.923 (2H, q, J = 8.0 Hz), 4.115 (1H, m), 5.3 - 6.2 (IH, br), 7.400 (2H, m), 7.650 (1H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 85℃; for 4.16667h;Inert atmosphere; | 5-Amino-6-chloro-3-(l-N-mPEG3-piperidin-4-yl)amino-l,2,4-triazine (189.9 mg, 0.51 mmol) was dissolved in dioxane (10 mL). (2,3-Dichlorophenyl)boronic acid (262.6 mg, 1.38 mmol) and cesium carbonate (699.6 mg, 2.13 mmol) were added. And then water (2.5 mL) was added. Tetrakis(triphenylphosphine)palladium (160.6 mg, 0.14 mmol) was added. The mixture was purged with nitrogen for a few minutes, and then heated to 85 C during 40 min, and kept at 85 C for 3.5 h. The mixture was concentrated under reduced pressure to dryness. The residue was mixed with water, extracted with dichloromethane (4 x 20 mL). The organic solution was concentrated. The residue was purified with column chromatography on silica gel using 1-10% methanol/dichloromethane to afford product (166.2 mg, Yield: 68%). NMR (500 MHz, Chloroform- /) δ 7.551 (dd, J= 2.0 Hz and 7.5 Hz, 1H), 7.362-7.308 (m, 1H), 4.735 (br, 2H), 3.920 (br, 1H), 3.648-3.609 (m, 10H), 3.545-3.526 (m, 2H), 3.362 (s, 3H), 2.914 (br, 2H), 2.604 (br, 2H), 2.245 (br, 2H), 2.058 (br, 2H), 1.61 1 (m, 3H). LC-MS: 485.0 (MHVz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 90℃; for 4h;Inert atmosphere; | (2,3-Dichlorophenyl)boronic acid (476.8 mg, 2.499 mmol) and 5-amino-6-chloro-3- (4-(N,N-methyl (111PEG3) amino)piperidin-l-yl)-l,2,4-triazine (349.7 mg, 0.899 mmol) was dissolved in water/dioxane (5/15 mL). Cesium carbonate (1.0573 g, 3.21 mmol) was added. The mixture was degassed with nitrogen, tetrakis(triphenylphosphine)palladium (99.7 mg, 0.086 mmol) was added. The mixture was purged with nitrogen for a few minutes, and then heated to 90 C during 15 min, and kept at 90 C for 4 h. The mixture was concentrated under reduced pressure to dryness. The residue was mixed with brine, extracted with dichloromethane (4 x 20 mL). The organic solution was concentrated. The residue was purified with column chromatography using 1-5% methanol in dichloromethane to afford product (244.6 mg) in 55% yield. NMR (500 MHz, Chloroform-;/) δ 7.54 (dd, J= 8.3, 1.8 Hz, 1H), 7.38 - 7.28 (m, 2H), 4.90 (d, J = 13.0 Hz, 2H), 4.67 (s, 2H), 3.62 (q, J = 3.4, 2.8 Hz, 8H), 3.53 (dd, J= 5.7, 3.7 Hz, 2H), 3.36 (s, 3H), 2.86 (t, J= 12.9 Hz, 2H), 2.71 (br, 3H), 2.33 (s, 3H), 1.87 (d, J= 12.5 Hz, 2H), 1.55 - 1.48 (m, 2H). MS for C22H32C12N603: 499.2 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 85℃; for 3.91667h;Inert atmosphere; | Tert-Butyl 4-((5-amino-6-chloro- 1 ,2,4-triazm-3-yl)amino)piperidine- 1 -carboxylate (250 mg, 0.76 mmol), (2,3-dichlorophenyl)boronic acid (392.9 mg, 2.06 mmol) and cesium carbonate (703.2 mg, 2.14 mmol) was dissolved in dioxane/water (10 mL/2.5 mL). Tetrakis(triphenyl phosphine)palladium (284.2 mg, 0.25 mmol) was added. The mixture was purged with nitrogen for a few minutes, and then heated to 85 C during 25 min, and kept at 85 C for 3.5 h. The mixture was concentrated under reduced pressure to dryness. The residue > was mixed with water, extracted with dichloromethane (4 x 20 mL). The organic solution was concentrated. The residue was purified with column chromatography on silica gel using 1- 10% methanol/dichloromethane to afford product (162.5 mg, Yield: 49%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 90℃; for 3.41667h;Inert atmosphere; | (2,3-Dichlorophenyl)boronic acid (515.2 mg, 2.70 mmol) and 3-amino-6-chloro-3- (l-Boc-piperidin-4-yl) piperazin-l-yl)-l,2,4-triazine (326.4 mg, 0.820 mmol) was dissolved Hn water/dioxane (5/15 mL). Cesium carbonate (1.0435 g, 3.17 mmol) was added. The mixture was degassed with nitrogen, tetrakis(triphenylphosphine)palladium (143.8 mg, 0.124 mmol) was added. The mixture was purged with nitrogen for a few minutes, and then heated to 90 C during 15 min, and kept at 90 <>C for 3 h. The mixture was concentrated under reduced pressure to dryness. The residue was mixed with brine, extracted with dichloromethane (2 x 20. mL). The organic solution was concentrated. The residue was purified with flash column chromatography on silica gel using 1-5% methanol/dichloromethane to afford 3-N-(l-Boc-(piperidin-4-yl)piperazin-l-yl) lamotrigine (320.8 mg) in 77% yield. NMR (500 MHz, Chloroforn /) δ 7.58 - 7.49 (m, 1H), 7.42 - 7.29 (m, 2H), 4.69 (s, 2H), 4.14 (br, 2H), 3.88 (s, 4H), 2.70 (s, 2H), 2.62 (t, J = 5.1 Hz, 4H), 2.42 (m, 1H), 1.81 (d, J = 1 1.0 Hz, 2H), 1.43 (s, 9H), 1.41 (m, 2H). MS for C23H31 CI2N7O2: 508.2 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 90℃; for 4h;Inert atmosphere; | (2,3-Dichlorophenyl)boronic acid (363. l mg, 1.903 mmol) and 5-amino-6-chloro-3- [4-Boc-3-(s)-(hydroxymethyl)piperazin-l -yl] 1 ,2,4-triazine (215.6 mg, 0.625 mmol) was dissolved in water/dioxane (5/15 mL). Cesium carbonate (733.6 mg, 2.229 mmol) were added. The mixture was degassed with nitrogen, tetrakis(triphenylphosphine)palladium (139.6 mg, 0.121 mmol) was added. The mixture was purged with nitrogen for a few minutes, and then heated to 90 C during 10 min, and kept at 90 OC for 4 h. The mixture was concentrated under reduced pressure to dryness. The residue dissolved in dichloromethane, washed with brine, dried over anhydrous sodium sulfate, concentrated. The residue was dissolved in methanol (5 mL), ammonium hydroxide (20 mL) was added to afford a white suspension. The mixture was stirred at r. t. for 4 h. The mixture was concentrated to remove all of solvents. The residue was separated with NH-column using 0-10% methanol in dichloromethane to afford 5-amino-3-[4-Boc-3-(s)-(hydroxymethyl)piperazin-l-yl] lamotrigine (205.5 mg) in 72% yield. MS for C 19H24CI2N6O3: 455.0 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 90℃; for 5h;Inert atmosphere; | (2,3-Dichlorophenyl)boronic acid (285.2mg, 1.495 mmol) and (R)-7-(5-amino-6- chloro-l,2,4-triazin-3-yl)tetrahydro-lH-oxazolo[3,4-a]pyrazin-3(5H)-one(179.6 mg, 0.664 mmol) was dissolved in water/dioxane (5/15 mL). Cesium carbonate (722.5 mg, 2.195 mmol) were added. The mixture was degassed with nitrogen, tetrakis(triphenylphosphine)palladium (120.2 mg, 0.104 mmol) was added. The mixture was purged with nitrogen for a few minutes, and stirred at 90 C for 5 h. The mixture was concentrated to remove organic solvents. The & residue was dissolved in dichloromethane (30 mL). Water (10 mL) was added and brine (40 mL) was added. The organic solution was separated and the aqueous solution was extracted with dichloromethane (2 x 50 mL). The combined organic solution was dried over anhydrous sodium sulfate, concentrated. The residue was purified with flash column chromatography on silica gel using 30-100% ethyl acetate /hexane to afford product as white solid (155.8 mg) in 62% yield. 1H NMR (500 MHz, Chloroform-i/) δ 7.60 - 7.53 (m, 1H), 7.37 - 7.29 (m, 2H), 5.07 (d, J = 12.7 Hz, 1H), 4.85 (d, J = 13.7 Hz, 1H), 4.77 (s, 2H), 4.45 (dd, J = 8.9, 8.2 Hz, 1H), 4.01 (dd, J= 9.0, 5.6 Hz, 1H), 3.95 - 3.84 (m, 2H), 3.1 1 (td, J= 12.8, 3.7 Hz, 1H), 2.96 (td, J = 12.8, 3.7 Hz, 1H), 2.84 (dd, J = 13.0, 11.0 Hz, 1H). MS for Ci5U{4C 602: 381.0 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 90℃; for 4h;Inert atmosphere; | (2,3-Dichlorophenyl)boronic acid (225.6mg, 1.182 mmol) and (S)-7-(5-amino-6- chloro-l ,2,4-triazin-3-yl)tetrahydro-lH-oxazolo[3,4-a]pyrazin-3(5H)-one (164.8 mg, 0.609 mmol) and cesium carbonate (701.2 mg, 2.131 mmol) were dissolved in water/dioxane (5/15 mL). The mixture was degassed with nitrogen, tetrakis(triphenylphosphine)palladium (1 15.9 mg, 0.100 mmol) was added. The mixture was purged with nitrogen for a few minutes, and stirred at 90 OC for 4 h. The mixture was concentrated to remove organic solvents. The residue was dissolved in dichloromethane (30 mL). Water (10 mL) was added and brine (40 mL) was added. The organic solution was separated and the aqueous solution was extracted with dichloromethane (2 x 50 mL). The combined organic solution was dried over anhydrous sodium sulfate, concentrated. The residue was purified with flash column chromatography on silica gel to afford slight yellow solid (104.8 mg) as product in 45% yield. NMR (500 MHz, Chloroform-i/) δ 7.58 (dd, J = 5.7, 3.9 Hz, IH), 7.38 - 7.31 (m, 2H), 5.08 (d, J = 12.5 Hz, IH), 4.86 (d, J = 13.6 Hz, IH), 4.79 (s, 2H), 4.47 (t, J = 8.6 Hz, IH), 4.02 (dd, J = 9.0, 5.6 Hz, IH), 3.96 - 3.85 (m, 2H), 3.12 (td, J - 12.7, 3.7 Hz, IH), 2.98 (td, J = 12.8, 3.7 Hz, IH), 2.85 (dd, J= 13.0, 11.0 Hz, IH). MS for Ci5H14Cl2N602: 381.0 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 90℃; for 5h;Inert atmosphere; | (2,3-Dichlorophenyl)boronic acid (0.934 g, 4.89 mmol), l-(5-amino-6-chloro- 1 ,2,4- triazin-3-yl)azetidin-3-ol (457.7 mg, 2.27 mmol) and cesium carbonate (2.2244 g, 6.76 mmol) was dissolved in water/dioxane (5/15 mL). The mixture was degassed with nitrogen, tetrakis(triphenylphosphine)palladium (315.1 mg, 0.273 mmol) was added. The mixture was purged with nitrogen for a few minutes, and stirred at 90 C for 5 h. The mixture was concentrated to remove organic solvents. The residue was mixed with a mixture of dichloromethane and water, sonicated for a few minutes. The mixture was filtered and the solid was washed with dichloromethane and dried under high vacuum to afford product (560.0 mg) in 79% yield. NMR (500 MHz, Methanol-^) δ 7.67 (dd, J= 8.1, 1.6 Hz, 1H), 7.43 (t, J = 7.8 Hz, 1H), 7.36 (dd, J = 7.7, 1.6 Hz, I H), 4.69 (tt, J = 6.6, 4.4 Hz, 1H), 4.37 (ddd, J = 9.5, 6.6, 1.2 Hz, 2H), 3.94 (ddd, J = 9.5, 4.4, 1.2 Hz, 2H). MS for C^HnC NsO: 312.0 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 90℃; for 5h;Inert atmosphere; | (2,3-Dichlorophenyl)boronic acid (0.3392 g, 1.778 mmol), (R)-8-(5-amino-6-chloro- l,2,4-triazin-3-yl)hexahydropyrazino[2,l-c][l,4]oxazin-4(3H)-one (244.1 mg, 0.857 mmol) and cesium carbonate (0.8478 g, 2.58 mmol) was dissolved in water/dioxane (5/15 mL). The mixture was degassed with nitrogen, tetrakis(triphenylphosphine)palladium (158.4 mg, 0.137 mmol) was added. The mixture was purged with nitrogen for a few minutes, and stirred at 90 C for 5 h. The mixture was concentrated to remove organic solvents. The residue was mixed with brine, extracted with dichloromethane (3 x 50 mL). The combined organic solution was dried over anhydrous sodium sulfate, concentrated. The residue was purified with flash column chromatography on silica gel using 30-100% ethyl acetate in hexane to afford yellow solid as product (290.1 mg) in 86% yield. 1H NMR (500 MHz, Chloroform-i/) δ 7.57 (dd, J= 6.3, 3.3 Hz, 1H), 7.35 (q, J = 3.8, 3.2 Hz, 2H), 4.90 - 4.82 (m, 2H), 4.79 (s, 2H), 4.71 - 4.64 (m, 1H), 4.24 - 4.16 (m, 2H), 4.12 - 4.02 (m, 2H), 3.70 - 3.58 (m, 2H), 3.01 (td, J = 12.9, 3.4 Hz, IH), 2.89 - 2.77 (m, 2H). MS for 395.0 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 90℃; for 4.75h;Inert atmosphere; | (2,3-Dichlorophenyl)boronic acid (0.450.4 g, 2.360 mmol), (S)-6-chloro-3- (hexahydropyrazino[2,l-c][l,4]oxazin-8(lH)-yl)-l,2,4-triazin-5-amine (282.3 mg, 1.043 mmol) and cesium carbonate (1.1547 g, 3.51 mmol) was dissolved in water/dioxane (5/15 mL). The mixture was degassed with nitrogen, tetrakis(triphenylphosphine)palladium (178.5 mg, 0.154 mmol) was added. The mixture was purged with nitrogen for a few minutes, and stirred at 90 C for 4 h 45 min. The mixture was concentrated to remove organic solvents. The residue was mixed with brine, extracted with dichloromethane (3 x 50 mL). The combined organic solution was dried over anhydrous sodium sulfate, concentrated. The residue was purified with flash column chromatography on silica gel using 30-100% ethyl acetate in hexane and 10% methanol in ethyl acetate to afford a yellow solid (376.8 mg) in 95% yield. NMR (500 MHz, Chloroform-;/) δ 7.55 (dd, J = 7.4, 2.3 Hz, IH), 7.38 - 7.29 (m, 2H), 4.77 (s, IH), 4.72 (s, 2H), 4.59 (d, J = 12.6 Hz, I H), 3.87 (dd, J= 11.4, 3.3 Hz, IH), 3.79 (dd, J = 1 1.1, 3.1 Hz, I H), 3.73 (td, J = 11.5, 2.4 Hz, IH), 3.32 (t, J = 11.1, 10.2 Hz, IH), 3.14 (td, J = 12.7, 3.2 Hz, IH), 2.87 - 2.80 (m, IH), 2.71 (d, J= 11.7 Hz, IH), 2.63 (dd, J= 12.8, 10.9 Hz, IH), 2.46 - 2.23 (m, 3H). MS for C^sC NeO: 381.0 (MH+). |
Tags: 2,3-Dichlorophenylboronic acid | Benzene Compounds | Chlorides | Organoboron | Aryls | Boronic Acids | Organic Building Blocks | Boronic Acids/Esters | Organometallic Reagents | 151169-74-3
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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 |
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