2-tert-butylimino-N,N-diethyl-1-methyl-1,3,2lambda5-diazaphosphinan-2-amine → 3-(1-Amino-isoquinolin-6-yloxy)piperidin-1--carboxylic acid tert-butyl ester

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Reaction Conditions

Reaction Steps

For an alternate procedure for the preparation of (S)-3-(1-amino-isoquinolin-6-yloxy)piperidin-1-carboxylic acid tert-butyl ester, a suspension of 1-amino-6-hydroxyisoquinoline (0.8 g, 5.0 mmol), (R)-3-methanesulfonyloxypiperidine-1-carboxylic acid tert-butyl ester (1.76 g) and 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine on polystyrene (3.4 g, −2.2 mmol/g loading) in acetonitrile (10 ml) were heated at 160° C. over a period of 15 minutes using the microwave. The excess supported regent was removed by filtration, washing with acetonitrile followed by methanol, and the filtrate evaporated to dryness under reduced pressure. Purification was achieved by chromatography on silica (eluent: 2-10% methanol in ethyl acetate) to afford (S) 3-(1-amino-isoquinolin-6-yloxy)piperidin-1-carboxylic acid tert-butyl ester (72 mg), El-MS: m/z=344.1 [M+H]+.

Provenance & Evidence