特布他林杂质59

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 0.057 M DMD in acetone (47.4 ml, 2.7 mmol) was added to a cold stirred solution of N-tert-butyl-N-benzylamine (Aldrich, 0.4417 g, 2.7 mmol) in acetone (5 ml). The reaction mixture was stirred for fifteen minutes in an ice bath. Solvent was removed on a rotary evaporator to give a white, microcrystalline solid (0.4803 g, 99.6% yield), mp 58-60. Flash chromatography of the solid over silica gel and elution with a 90:10 mixture of petroleum ether (bp 35-60) and ethyl acetate gave the hydroxylamine as a white crystalline solid, mp 60-61.5 (reported mp 71-73, Emmons 1957). Distillation of this material gave a solid with the same mp. Solvent was removed on a rotary evaporator

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred and cooled mixture of 33 parts of N-benzyl-N-tert.-butylamine in 60 parts of sodium hydroxide solution 20% and 160 parts of 1,2-dichloroethane are added dropwise 34 parts of 2-chloroacetyl chloride at a temperature between -5° and -10° C. Upon completion, stirring is continued at the same temperature for one hour. The reaction mixture is allowed to reach room temperature and the organic layer is separated, washed with water, dried and evaporated, yielding 43 parts of N-benzyl-N-tert.-butyl-2-chloroacetamide as a residue. cooled Upon completion, stirring to reach room temperature the organic layer is separated washed with water dried evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of (3-oxo-5H-thiazolo[2,3-b]quinazolin-2(3H)-ylidene)acetic acid (1.3 g, 5 mmols), triethylamine (1.5 ml, 0.01 mol), and N-(tert-butyl)benzylamine (0.93 ml, 5 mmols) in 10 ml dichloromethane, was cooled to 10° C. Then, 1.27 g (5 mmols) of N,N-bis(2-oxo-3-oxazolidinyl)phosphorodiamidic chloride was added, and the reaction mixture was stirred at room temperature for 20 hours. Following acidification with dilute hydrochloric acid, the reaction mixture was filtered and the organic layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated to dryness under reduced pressure leaving an orange-yellow solid which was recrystallized from anhydrous ethanol. Yield--0.71 g. Mp 195°-197° C. the reaction mixture was filtered the organic layer was washed with water dried over anhydrous magnesium sulfate evaporated to dryness under reduced pressure leaving an orange-yellow solid which was recrystallized from anhydrous ethanol Yield--0.71 g

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The compound, (3-oxo-5H-thiazolo[2,3-b]quinazolin-2(3H)-ylidene)acetic acid (compound IIIa), triethylamine, and N-(tert-butyl)benzylamine, in relative molar amounts of 1, 2, and 1, respectively, are dissolved in dichloromethane, and the solution is cooled to 10° C. The compound, N,N-bis(2-oxo-3-oxazolidinyl)phosphorodiamidic chloride, (relative molar amount, 1) is added to the reaction mixture, which is then stirred at about 25° C. for about 2 hours. Following acidification with dilute hydrochloric acid, the reaction mixture is filtered, and the organic phase is washed with water, dried over anhydrous magnesium sulfate, and evaporated to dryness under reduced pressure, leaving the N-tert-butyl-N-benzyl(3-oxo-5H-thiazolo[2,3-b]quinazolin-2(3H)-ylidene)acetamide as a solid. The N-tert-butyl-N-benzyl(3-oxo-5H-thiazolo[2,3-b]quinazolin-2(3H)-ylidene)acetamide (compound VI) is then recrystallized from anhydrous ethanol. Replacement of (3-oxo-5H-thiazolo[2,3-b]2(3H)-ylidene)acetic acid with a derivative thereof in which a nuclear hydrogen of the benzene ring has been substituted with lower alkyl, alkoxy, halogen, trifluoromethyl, NO2 or NH2, results in the formation of the corresponding derivative of N-tert-butyl-N-benzyl(3-oxo-5H-thiazolo[2,3-b]quinazolin-2(3H)-ylidene)acetamide. the reaction mixture is filtered the organic phase is washed with water dried over anhydrous magnesium sulfate evaporated to dryness under reduced pressure

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The compound, (3-oxo-5H-thiazolo[2,3-b]quinazolin-2(3H)-ylidene)acetic acid (compound IIIa), triethylamine, and N-(tert-butyl)benzylamine, in relative molar amounts of 1, 2, and 1, respectively, are dissolved in dichloromethane, and the solution is cooled to 10° C. The compound, N,N-bis(2-oxo-3-oxazolidinyl)phosphorodiamidic chloride, (relative molar amount, 1) is added to the reaction mixture, which is then stirred at about 25° C. for about 2 hours. Following acidification with dilute hydrochloric acid, the reaction mixture is filtered, and the organic phase is washed with water, dried over anhydrous magnesium sulfate, and evaporated to dryness under reduced pressure, leaving the N-tert-butyl-N-benzyl(3-oxo-5H-thiazolo[2,3-b]quinazolin-2(3H)-ylidene)acetamide as a solid. The N-tert-butyl-N-benzyl(3-oxo-5H-thiazolo[2,3-b]quinazolin-2(3H)-ylidene)acetamide (compound VI) is then recrystallized from anhydrous ethanol. Replacement of (3-oxo-5H-thiazolo[2,3-b]2(3H)-ylidene)acetic acid with a derivative thereof in which a nuclear hydrogen of the benzene ring has been substituted with lower alkyl, alkoxy, halogen, trifluoromethyl, NO2 or NH2, results in the formation of the corresponding derivative of N-tert-butyl-N-benzyl(3-oxo-5H-thiazolo[2,3-b]quinazolin-2(3H)-ylidene)acetamide. the reaction mixture is filtered the organic phase is washed with water dried over anhydrous magnesium sulfate evaporated to dryness under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Albuterol has been prepared, see Irish Patent Specification No. 31391, Aug. 9, 1972, starting from the appropriate acetophenone derivative methyl-5-(bromoacetyl-2-hydroxybenzoate, by condensation with N-(1,1-dimethylethyl)benzenemethanamine in the presence of base to form the ketonic ester, methyl-5[[(1,1-dimethylethyl)(phenylmethyl)-amino]acetyl]-2-hydroxybenzoate. The ketonic ester is reduced with lithium aluminum hydride in tetrahydrofuran under nitrogen to yield α1 -[[(1,1-dimethylethyl)-(phenylmethyl)amino]methyl]-4-hydroxy-1,3-benzenedimethanol which is subsequently debenzylated with hydrogen in the presence of palladium on carbon catalyst to produce albuterol.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 8.0 g of 3',5'-bis-(N-ethylcarbamoyloxy)-2-bromo acetophenone in 100 ml of acetone was added 7.0 g of N-benzyl-t-butylamine. The mixture was refluxed for 18 hours. The 4.1 g of N-benzyl-t-butylamine hydrobromide formed and precipitated during the reaction was filtered off and the filtrate was acidified with conc HCl. The filtrate was now evaporated to dryness and the title compound was isolated by column chromatography on Silica gel 60 using 1) CHCl3 /ethanol (2:1), 2) ethanol as eluants. The title compound was eluted in the ethanol fraction and recrystallized from ethanol/diethylether. The identity of the product was confirmed with NMR. The mixture was refluxed for 18 hours