Dichloromethane → 1-Isoquinolinecarboxamide

Participants

Reaction Conditions

Reaction Steps

In Scheme 1, step A, a protected 3,4-dihydro-1H-isoquinoline-3-carboxylic acid, wherein Pg is a suitable nitrogen protecting group, such as a tert-butoxy carbonyl protecting group (BOC), is coupled with methyl 4-(1-aminoethyl)benzoate under standard conditions to provide the protected isoquinoline amide of structure (1). For example, the protected 3,4-dihydro-1H-isoquinoline-3-carboxylic acid is dissolved in a suitable organic solvent, such as dichloromethane, cooled to about 0° C., and treated with about 1.1 equivalents of a suitable organic base, such as triethylamine. Then about 1.1 equivalents of isobutyl chloroformate are added dropwise with stirring. The mixture is allowed to stir for about 20 minutes at 0° C., followed by addition of about 1.1 equivalents of the methyl 4-(1-aminoethyl)benzoate. The reaction mixture is then stirred for about 1 hour at room temperature. The protected isoquinoline amide (1) is then isolated using methods well known in the art, such as extraction techniques. For example, water is added to the mixture, the layers are separated, and the organic phase is washed with aqueous potassium bisulfate, followed by aqueous sodium bicarbonate. The organic phase is then dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to provide the protected isoquinoline amide (1).

Provenance & Evidence