Diisopropylethylamine → HCID 178505028, compound

Participants

Reaction Conditions

Reaction Steps

Diisopropylethylamine (0.33 mL, 1.89 mmol) was added to a solution of N-[5-(2-{{4-[4-(4-aminobutyl)phenyl]butyl}-[2-(R)-hydroxy-2-(4-hydroxy-3-methanesulfonyl-aminophenyl)ethyl]amino}-1-(R)-hydroxyethyl)-2-hydroxyphenyl]methanesulfonamide diacetic acid salt (41) (0.30 g, 0.375 mmol) in absolute ethanol (5 mL). The mixture was stirred at 70° C. (oil bath) for 15 min, after which 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (0.16 g, 0.41 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 25%), and further purified by preparative HPLC eluting with a gradient acetonitrile and water, each containing 0.01% concentrated ammonium hydroxide, to give the desired adduct 42 as a greenish yellow solid (78 mg, 23%): 1H NMR (500 MHz, DMSO-d6) δ 1.50 (m, 8H), 2.58 (m, 4H), 2.88 (s, 6H), 3.20 (m, 5H), 4.48 (m, 2H), 6.60 (br, 2H), 6.78 (d, 2H), 6.90 (d, 2H), 7.10 (s, 4H), 7.18 (s, 2H); m/z (ESI) 891 [C38H51ClN10O9S2+H]+; [α]D25 −23.0° (c 0.40, MeOH); mp 148-150° C.

Provenance & Evidence