Ethanol → 4-{[(2R)-2,3-Dihydroxypropyloxy]phenyl}butylamine

Participants

Reaction Conditions

Reaction Steps

Compound 69 (0.112 g, 0.269 mmol) was mixed with ethanol (5 mL). The mixture was heated at 65° C. for 15 min to achieve complete dissolution. To the clear solution were sequentially added triethylamine (23 μL, 0.161 mmol) and 1-(3,5-diamino-6-chloropyrazinoyl)-2-methylisothiourea hydriodide (0.105 g, 0.269 mmol). The mixture was heated at 65° C. for an additional 2 hours. It was, while still warm, slowly added into methyl tert-butyl ether (MTBE, 25 mL) cooled by an ice bath. A light yellow precipitation immediately formed upon the addition of the reaction mixture. The suspension was allowed to warm up to room temperature by removing the ice bath, and the stirring was continued for one more hour. The solid was vacuum filtered, washed with MTBE (3×5 mL), and tried under vacuum for 4 hours. The dry material (0.155 g) was then suspended in ethanol (3 mL), and treated with concentrated HCl (1 mL). Water (3 mL) was added to completely dissolve the solid. The resulting solution was concentrated to dryness under vacuum. The residue was taken into methanol (2 mL). The resultant methanolic solution was added into 2-propyl alcohol (15 mL) at room temperature. The resulting light yellow suspension was stirred at room temperature overnight. The solid was then vacuum filtered, washed with 2-propyl alcohol (3×3 mL), and dried under vacuum. 0.093 g (49%) of the compound 70 was obtained as a light yellow solid. [α]D25=−13.9° (c 1.0, MeOH). 1H NMR (300 MHz, DMSO-d6) δ 1.46-1.68 (m, 4H), 2.50-2.57 (m, 2H), 3.26-3.70 (m, 15H), 3.88-4.98 (m, 2H), 4.35-4.72 (m, 2H), 4.98-5.10 (br s, 2H), 5.50-6.70 (br s, 2H), 6.93 (d, J=8.3 Hz, 2H), 7.16 (d, J=8.3 Hz, 2H), 7.45 (br s, 2H), 7.84-8.06 (br s, 1H), 8.61 (br s, 1H), 8.81 (br s, 1H), 8.94 (br s, 1H), 9.25 (br s, 1H), 10.51 (br s, 1H). m/z (APCI)=629 [C26H41ClN8O8+H]+.

Provenance & Evidence