4602 J ournal of Medicinal Chemistry, 1999, Vol. 42, No. 22
Brundish et al.
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of hot ethanol. Evaporation of the combined extracts by
lyophilization from dilute acetic acid solution gave the stable
solid acetate salt 49 (100 mg, 47.6%): TLC Rf ) 0.18 (CHCl3/
MeOH/AcOH, 6:1:1); 1 main peak by HPLC [Zorbax C8,
gradient elution (35 min) CH3CN/H2O/TFA, 0:1000:1 to 950:
50:1]. Anal. (C27H43N7O6S‚2CH3COOH‚0.5H2O) C, H, N, S.
[2-(2-{1-[5-Gu an idin o-2(S)-(3(RS)-m eth yl-1,2,3,4-tetr ah y-
d r oq u in olin -8-ylsu lfon yla m in o)p en t a n oyl]p ip er id in -4-
yl}eth ylca r ba m oyl)eth yl]p h osp h on ic Acid (50). Analo-
gously as described for 42b (steps a-c) but using [2-(2-
piperidin-4-ylethylcarbamoyl)ethyl]phosphonic acid diethyl
ester acetate salt (27c) (513 mg) in place of acetic acid
2-piperidin-4-ylethyl ester hydrochloride was prepared [2-(2-
{1-[5-guanidino-2(S)-(3(RS)-methyl-1,2,3,4-tetrahydroquinolin-
8-ylsulfonylamino)pentanoyl]piperidin-4-yl}ethylcarbamoyl)-
ethyl]phosphonic acid diethyl ester which was stirred in
saturated hydrogen bromide in acetic acid (5 mL) at 20 °C for
16 h. The solvent was removed by rotary evaporation and the
oily residue obtained triturated with dry ether to afford a solid
which was purified by gel filtration chromatography to give
50 as a solid after lyophilization (165 mg, 35%). Anal.
(C26H44N7O7SP‚2.5H2O) C, H, N, S, P.
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