CN([CH:4]=[O:5])C.P(Cl)(Cl)(Cl)=O.[CH2:11]([C:13]1[C:14]([NH:20][CH2:21][CH2:22][NH:23][C:24](=[O:26])[CH3:25])=[C:15]([OH:19])[CH:16]=[CH:17][CH:18]=1)[CH3:12].[OH-].[Na+]>O>[OH:19][C:15]1[C:14]([NH:20][CH2:21][CH2:22][NH:23][C:24](=[O:26])[CH3:25])=[C:13]([CH2:11][CH3:12])[CH:18]=[CH:17][C:16]=1[CH:4]=[O:5]A scrupulously dry flask was charged with anhydrous DMF (15 ml) and cooled in ice under argon. Phosphorus oxychloride, POCl3, 1.5 ml (1.15 eq) was added slowly dropwise to the stirred solution. After the addition was complete, the flask was removed from the ice bath and allowed to reach ambient temperature. This was accompanied by a color change to yellow. The flask was heated in a 40° C. bath for one hour. It was removed from the heat, and once at ambient temperature, a DMF solution of 3-(ethyl)(2-acetylaminoethyl)aminophenol (8; 3.2 g, 14 mmol) was added via addition funnel. After the addition was complete, the flask was returned to the 40° C. bath and stirred overnight. The reaction was cooled to 0° C. and 25 ml 10% NaOH was added, the mixture was allowed to warm to ambient temperature and was then placed in a 40° C. bath. Additional NaOH was added to achieve pH>10. Water (50 ml) was added. After 15 minutes the flask was removed from the bath and the pH adjusted to 5–5.5 with 1N HCl. The mixture was transferred to a separatory funnel and extracted with 4×100 ml ethyl acetate. The pooled organic fractions were washed with water (1×75 ml), predried with Na2SO4, and then dried with MgSO4 overnight. The solution was collected by filtration and the volatiles removed by rotary evaporation to yield the crude product (2.9 g). The material was purified by flash chromatography on silica, 45×150 mm column, eluting with 200 ml each of 2.5%, 5%, and 10% methanol/chloroform. Purified yield of (2-hydroxy-4-(ethyl)(2-acetylaminoethyl)aminobenzaldehyde) (9) was 1.52 g (45%).
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