Реакция #219752

Уравнение реакции

2-[4-(4-aminobutyl)phenoxy]-N-(1H-imidazol-2-yl)acetamide dihydrochloride

2-[4-(4-Aminobutyl)phenoxy]-N-(1H-imidazol-2-yl)acetamide dihydrochloride

diisopropylethylamine

1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide

→

2-(4-{4-[N′-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidino]butyl}phenoxy)-N-(1H-imidazol-2-yl)-acetamide

Выход 32.5%

Растворители

ethanol

methanol

Условия реакции

Обработка

1. 1
   ДругоеThe yellow insolubles were removed by suction filtration
2. 2
   Концентрированиеthe liquid filtrate was concentrated by rotary evaporation
3. 3
   ДругоеThe crude residue was purified by flash silica gel column chromatography
4. 4
   Промывкаeluting with dichloromethane/methanol/concentrated ammonium hydroxide (200:10:0,200:10:1, 150:10:1, and 100:10:1

Методика

A solution of 2-[4-(4-aminobutyl)phenoxy]-N-(1H-imidazol-2-yl)acetamide dihydrochloride 35 (99 mg, 0.27 mmol) and diisopropylethylamine (0.27 mL, 1.53 mmol) in absolute ethanol (4 mL) and anhydrous methanol (3 mL) was stirred at 70° C. for 30 min, after which 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (130 mg, 0.34 mmol) was added in one portion. The reaction mixture was stirred for 3 h and then cooled to room temperature. The yellow insolubles were removed by suction filtration and the liquid filtrate was concentrated by rotary evaporation. The crude residue was purified by flash silica gel column chromatography eluting with dichloromethane/methanol/concentrated ammonium hydroxide (200:10:0,200:10:1, 150:10:1, and 100:10:1, v/v) to give 2-(4-{4-[N′-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidino]butyl}phenoxy)-N-(1H-imidazol-2-yl)-acetamide as a yellow solid (44 mg, 29% yield). The free base thus obtained was dissolved in methanol and treated with 4 drops of 4 N aqueous HCl. The solution was concentrated under reduced pressure and further dried under vacuum to give the final compound 36. mp 172-1740C. 1H NMR (300 MHz, CD3OD) δ 1.61-1.77 (m, 4H), 2.58-2.70 (m, 2H), 3.32-3.40 (m, 2H), 4.80 (s, 2H), 7.00 (d, 2H), 7.18 (d, 2H), 7.20 (s, 2H). m/z (ESI): 501 [C21H25ClN10O3+H]+.

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