Structure of 527-62-8
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 527-62-8 |
Formula : | C6H5Cl2NO |
M.W : | 178.02 |
SMILES Code : | C1=C(Cl)C=C(C(=C1N)O)Cl |
MDL No. : | MFCD00035766 |
InChI Key : | WASQBNCGNUTVNI-UHFFFAOYSA-N |
Pubchem ID : | 10699 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319-H335 |
Precautionary Statements: | P261-P280-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 |
---|---|---|
60% | With sodium dithionite; In ethanol; water; at 65℃; for 4h; | To a suspension of 2, 4-dichloro-6-nitrophenol (60.0 g, 288 mmol) in ethanol (250 mL) and water (250 mL) was added portionwise sodium hydrosulfite (251 g, 1.44 mmol). The mixture was stirred at 65C for 4 h. The mixture was concentrated in vacuo, diluted with saturated aqueous sodium hydrogen carbonate solution (500 mL) , extracted with ethyl acetate (200 mL X 4 ) and washed with brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel EPO <DP n="81"/>eluting with a 0-50% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was washed with n-hexane to give the title compound (30.6 g, 172 mmol, 60%) as a colorless powder. 1H NMR (CDCl3) δ 3.92 (s, 2H), 5.36 (s, IH), 6.59 (d, J = 2.1 Hz, IH), 6.71 (d, J = 2.1 Hz, IH). MS Calcd.: 177; MS Found: 178 (M+H) . |
10% | In aqueous ammonium acetate; 2-amino-6-chlorophenol; acetonitrile; | a 2-Amino-4,6-dichlorophenol 2-Amino-4,6-dichlorophenol was prepared from <strong>[609-89-2]2,4-dichloro-6-nitrophenol</strong> (0.625 g, 2.40 mmol) in a manner similar to that described for 2-amino-6-chlorophenol. The compound was formed as a black solid (0.044g, 10%). RP-HPLC (25 to 100% CH3CN in 0.1 N aqueous ammonium acetate over 10 min at 1 mL/min using a Hypersil HS C18, 100 Å, 5 μm, 250*4.6 mm column) tr=9.033 min., 74%; m/z 177 (MH+). |
10% | In aqueous ammonium acetate; 2-amino-6-chlorophenol; acetonitrile; | a) 2-amino-4,6-dichlorophenol 2-amino-4,6-dichlorophenol was prepared from <strong>[609-89-2]2,4-dichloro-6-nitrophenol</strong> (0.625 g, 2.40 mmol) in a manner similar to that described for 2-amino-6-chlorophenol. The compound was formed as a black solid (0.044 g, 10%). RP-HPLC (25 to 100% CH3CN in 0.1 N aqueous ammonium acetate over 10 min at 1 mL/min using a Hypersil HS C18, 100 Å, 5 μm, 250*4.6 mm column) tr=9.033 min., 74%; m/z 177 (MH+). |
With hydrogenchloride; sodium hydroxide; In methanol; water; | Synthesis of 2-amino-4,6-dichlorophenol The starting material, <strong>[609-89-2]2,4-dichloro-6-nitrophenol</strong> (260 g, 1 mole, 20% in water), was mixed with methanol (2 liters) and platinum oxide catalyst, and the resulting slurry was reacted with hydrogen at 4.2 kg/cm2 (60 psi) and room temperature. The resulting solution was filtered to remove the catalyst and concentrated hydrochloric acid (150 ml) was added to the filtrate. The methanol was then removed by evaporation and the residual solid was redissolved in hot water (2 liters) with a little concentrated HCl added. The solution was filtered to remove dark, insoluble material and cooled to 30 C. Dilute NaOH solution was added until the pH was about 6, and the mixture was chilled in an ice bath. The resulting white solid was filtered off and dried at room temperature under nitrogen. The compound yield was about 142 g (80% of theoretical) and it had a m.p. of 93-95 C. | |
palladium; In acetic acid; | A. Preparation of 2,4-Dichloro-6-aminophenol A mixture of 10 g (0.048 moles) of <strong>[609-89-2]2,4-dichloro-6-nitrophenol</strong> and 0.2 g of 5% palladium on carbon slurried in 250 ml of glacial acetic acid was placed in a hydrogenation bottle. The bottle was stoppered under an atmosphere of 40 psi hydrogen and shaken at room temperature. The hydrogen was replenished during reaction. After four and one-half hours the hydrogen uptake was complete. The mixture then was filtered through a sintered glass funnel and the filtrate was stripped of solvent under reduced pressure. The yield of product was quantitative. | |
With hydrogen;nickel; In methanol; under 760.051 Torr; for 4h; | 60 g of 4,6 dichloro-2 nitrophenol were dissolved in 600 ml methanol and 5 g. Raney nickel were added. This solution was hydrogenated under atmospheric pressure for 4 hours and filtrated. After evaporation of methanol, the residue was crystallized in isopropyl ether to give 40.5 g of IA as a grey solid (mp=33 C.). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In ethanol; | a) Preparation of 2-amino-4,6-dichlorophenol A mixture of 4,6-dichloro-2-nitrophenol(1 g, 4.8 mmol) and tin (II) chloride (3.2 g, 14.4 mmol) in ethanol(50 mL) was heated at 80 C. under argon. After 2 hours, the starting material had disappeared and the solution was allowed to cool down and then poured into ice. The pH was made slightly basic (pH7-8), by addition of solid NaOH, before being extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4% MeOH/CH2 Cl2) gave the desired product(685 mg, 80%). 1 H NMR (CD3 OD): δ 6.75 (s, 1H), 6.61 (s, 1H). |
80% | In ethanol; | a)Preparation of 2-amino-4,6-dichlorophenol A mixture of 4,6-dichloro-2-nitrophenol(1 g, 4.8 mmol) and tin (II) chloride (3.2 g, 14.4 mmol) in ethanol(50 mL) was heated at 80 C. under argon. After 2 hours, the starting material had disappeared and the solution was allowed to cool down and then poured into ice. The pH was made slightly basic (pH7-8), by addition of solid NaOH, before being extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4%MeOH/CH2 Cl2) gave the desired product(685 mg, 80%). 1 H NMR (CD3 OD): d 6.75 (s,1H), 6.61 (s, 1H). |
80% | In ethanol; | a) Preparation of 2-amino-4,6-dichlorophenol A mixture of 4,6-dichloro-2-nitrophenol (1 g, 4.8 mmol) and tin (II) chloride (3.2 g, 14.4 mmol) in ethanol (50 mL) was heated at 80 C. under argon. After 2 hours, the starting material had disappeared and the solution was allowed to cool down and then poured into ice. The pH was made slightly basic (pH7-8), by addition of solid NaOH, before being extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4%MeOH/CH2CH2) gave the desired product (685 mg, 80 %). 1H NMR (CD3OD): d 6.75 (s, 1H), 6.61 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; sodium hydrogencarbonate; | EXAMPLE 6 2-Chloromethyl-5,7-dichlorobenzoxazole To a solution of <strong>[609-89-2]2,4-dichloro-6-nitrophenol</strong> (10.0 g) in water (450 ml) containing sodium bicarbonate (4.8 g) was added sodium dithionate in a quantity sufficient to turn the original dark solution colorless. The hot reaction mixture was filtered and the filtrate was cooled to room temperature and the crystallized product, 2-amino-4,6-dichlorophenol was collected (1.6 g). |