Diisopropylethylamine → HCID 178505027, compound

Participants

Reaction Conditions

Reaction Steps

Diisopropylethylamine (0.54 mL, 3.11 mmol) was added to a solution of N-[5-(2-{4-[4-(4-aminobutyl)phenyl]butylamino}-1-(R)-hydroxyethyl)-2-hydroxyphenyl]-methanesulfonamide diacetic acid salt (39) (0.30 g, 0.52 mmol) in absolute ethanol (8 mL). The mixture was stirred at 70° C. (oil bath) for 10 min, after which 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (0.2) g, 0.54 mmol) was added in one portion. The reaction mixture was stirred at that temperature for 3 h and cooled to rt. The solvent was removed by rotary evaporation. The residue was purified by Biotage silica gel column chromatography (A=dichloromethane, B=10% concentrated aqueous ammonium hydroxide in methanol, gradient B/A 0% to 15%), and further purified by semi-preparative HPLC eluting with a gradient acetonitrile and water, each containing 0.01% concentrated ammonium hydroxide, to give N-(5-{2-[4-(4-{4-[N′-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidino]butyl}phenyl)butylamino]-1-(R)-hydroxyethyl}-2-hydroxyphenyl)methanesulfonamide (40) as a greenish yellow solid (0.17 g, 48%): 1H NMR (500 MHz, CD3OD) δ 1.60 (m, 8H), 2.60 (m, 6H), 2.72 (m, 1H), 2.80 (m, 1H), 2.88 (s, 3H), 3.23 (m, 2H), 4.65 (m, 1H), 6.80 (d, 1H), 6.98 (d, 1H), 7.06 (m, 4H), 7.30 (s, 1H), m/z (ESI) 662 [C29H40ClN9O5S+H]+; [α]D25 −7.5° (c 0.60, MeOH); mp 108-110° C.

Provenance & Evidence