Sodium Bicarbonate → N-Butyl-N-(2-(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethylamino)ethyl)-3-(3-(2-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenethoxy)propanamide

Participants

Reaction Steps

p-Toluenesulphonic acid monohydrate (4 molar equivalents) was added to a solution of N-butyl-N-(2,2-dimethoxyethyl)-3-(3-(2-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenethoxy)propanamide (limiting reagent) in THF (10 volumes) and the resulting mixture stirred for 1 hour at room temperature. The solution was then added via a peristaltic pump to a suspension of 8-(2-aminoethyl)-5-hydroxy-2H-benzo[b][1,4]oxazin-3(4H)-one hydrochloride (1 molar equivalent) and sodium bicarbonate (6.5 molar equivalents) in a mixture of NMP (4 volumes) and water (0.45 volumes) which had been stirring at room temp for 1 hour. The resulting cloudy solution was stirred for 30 mins before sodium triacetoxyborohydride (3 molar equivalents) was added portionwise and the resulting mixture was stirred for 1 hour.

Provenance & Evidence