3-amino-5-methoxyphenol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-amino-5-methoxyphenol (Example 20, step i, 140 mg, 1.0 mmol), triphenylphosphine (390 mg, 1.5 mmol) and propan-2-ol (90 ul, 1.2 mmol) in THF (3 ml) was added portion wise di-tert-butyl diazocarboxylate (345 mg, 1.5 mmol) at room temperature. After stirring for 3 hours the reaction mixture was diluted with ethyl acetate and extracted with a 1N aqueous solution of HCl. The combined aqueous phases were brought to pH=10 with a aqueous solution of 1N NaOH and then extracted with ethyl acetate. The combined organics were filtered through a hydrophobic frit and the solvents were removed under reduced pressure to give 3-isopropoxy-5-methoxyaniline as a light brown oil (169 mg). extracted with a 1N aqueous solution of HCl extracted with ethyl acetate The combined organics were filtered through a hydrophobic frit the solvents were removed under reduced pressure

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3,5-dimethoxyaniline (2.53 g, 16.5 mmol) in N-methylpyrrolidinone (10 ml) was added sodium thiomethoxide (2.32 g, 33.1 mmol). The reaction mixture was heated to 140° C. for 2.5 hours and then stirred at ambient temperature for a further 18 hours. The mixture was poured into a saturated solution of NaH2PO4 (50 ml) and then extracted with ethyl acetate. The combined organic layers were filtered through a hydrophobic frit and the solvent was removed under reduced pressure to give a dark red oil. The crude residue was purified by normal phase chromatography, eluting with iso-hexane and increasing amounts of ethyl acetate to give 3-amino-5-methoxyphenol, as a pale yellow solid (1.53 g). extracted with ethyl acetate The combined organic layers were filtered through a hydrophobic frit the solvent was removed under reduced pressure to give a dark red oil The crude residue was purified by normal phase chromatography eluting with iso-hexane increasing amounts of ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-amino-5-methoxyphenol (5.44 g, 39.1 mmol), isopropyl alcohol (3.6 ml, 47 mmol) and triphenylphosphine (12.0 g, 47 mmol) in THF, was added diethyl azodicarboxylate (7.4 ml, 47 mmol). The reaction mixture was stirred for 16 h and the solvent was removed. The residue was purified by flash chromatography on silica gel eluting with 20% EtOAc/hexanes to afford the title compound (4.13 g). MS m/z: 182 [M+H]+ the solvent was removed The residue was purified by flash chromatography on silica gel eluting with 20% EtOAc/hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 65 mg (0.23 mmol) of 9-chloro-1,2-dihydrothieno[3,2-f]quinoline-8-carbonitrile 3,3-dioxide are refluxed together with 39 mg (1.2 eq., 0.28 mmol) of 3-hydroxy-5-methoxyaniline in 2 ml of isopropanol for 2 hours. After the reaction is complete, the crude product is mixed with water and sat. ammonium chloride solution, extracted 3× with dichloromethane/methanol, washed 1× with sat. sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. Final purification of the compound took place by chromatography. 20 mg (22%) of the desired product were obtained. extracted 3× with dichloromethane/methanol washed 1× with sat. sodium chloride solution dried over sodium sulphate concentrated in vacuo Final purification of the compound

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3,5-Dimethoxyaniline (9.97 g, 65.1 mmol) and sodium methyl mercaptide (9.1 g, 130 mmol) were dissolved in N-methylpyrrolidinone (60 ml). The reaction mixture was stirred at 140° C. for 1 h. After cooling to room temperature, the reaction mixture was partitioned between ethyl acetate and saturated aqueous Na2HPO4. The layers were separated and the organic layer was washed with water, dried over MgSO4 and the solvent was evaporated. The residue was purified by flash chromatography on silica gel eluting with 50% EtOAc/hexanes to afford 3-amino-5-methoxyphenol (5.44 g). MS m/z: 140 [M+H]+ After cooling to room temperature the reaction mixture was partitioned between ethyl acetate and saturated aqueous Na2HPO4 The layers were separated the organic layer was washed with water dried over MgSO4 the solvent was evaporated The residue was purified by flash chromatography on silica gel eluting with 50% EtOAc/hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-amino-5-methoxyphenol (Example 20, step i, 140 mg, 1.0 mmol), triphenylphosphine (390 mg, 1.5 mmol) and propan-2-ol (90 ul, 1.2 mmol) in THF (3 ml) was added portion wise di-tert-butyl diazocarboxylate (345 mg, 1.5 mmol) at room temperature. After stirring for 3 hours the reaction mixture was diluted with ethyl acetate and extracted with a 1N aqueous solution of HCl. The combined aqueous phases were brought to pH=10 with a aqueous solution of 1N NaOH and then extracted with ethyl acetate. The combined organics were filtered through a hydrophobic frit and the solvents were removed under reduced pressure to give 3-isopropoxy-5-methoxyaniline as a light brown oil (169 mg). extracted with a 1N aqueous solution of HCl extracted with ethyl acetate The combined organics were filtered through a hydrophobic frit the solvents were removed under reduced pressure

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3,5-dimethoxyaniline (2.53 g, 16.5 mmol) in N-methylpyrrolidinone (10 ml) was added sodium thiomethoxide (2.32 g, 33.1 mmol). The reaction mixture was heated to 140° C. for 2.5 hours and then stirred at ambient temperature for a further 18 hours. The mixture was poured into a saturated solution of NaH2PO4 (50 ml) and then extracted with ethyl acetate. The combined organic layers were filtered through a hydrophobic frit and the solvent was removed under reduced pressure to give a dark red oil. The crude residue was purified by normal phase chromatography, eluting with iso-hexane and increasing amounts of ethyl acetate to give 3-amino-5-methoxyphenol, as a pale yellow solid (1.53 g). extracted with ethyl acetate The combined organic layers were filtered through a hydrophobic frit the solvent was removed under reduced pressure to give a dark red oil The crude residue was purified by normal phase chromatography eluting with iso-hexane increasing amounts of ethyl acetate