Diisopropylethylamine → HCID 178512397, compound

Participants

Reaction Conditions

Reaction Steps

Diisopropylethylamine (0.13 mL, 0.72 mmol) was added to a solution of N-[5-(2-{4-[4-(4-aminobutyl)phenyl]butylamino}-1-(R)-hydroxyethyl)-2-hydroxyphenyl]formamide diacetic acid salt (11) (65 mg, 0.13 mmol) in absolute ethanol (5 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 (53 mg, 0.14 mmol) was added in two portions over 45 min. The reaction mixture was stirred at that temperature for 3 h and cooled to rt. 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 1% to 15%), and further purified by semi-preparative HPLC eluting with a gradient acetonitrile and water, each containing 0.05% 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)formamide (12) as a greenish yellow solid (35 mg, 46%): 1H NMR (500 MHz, DMSO-d6) δ 1.50 (m, 8H), 2.51 (m, 4H), 3.15 (m, 6H), 4.42 (m, 1H), 5.00 (br, 1H), 6.58 (br, 2H), 6.72 (m, 1H), 6.80 (m, 1H), 7.08 (m, 4H), 8.00 (s, 1H), 8.25 (s, 1H); m/z (ESI) 612 [C29H38ClN9O4+H]+; [α]D25 −3.3° (c 0.15, MeOH); mp 138-140° C.

Provenance & Evidence