تفاعل #481733

ord-6005e7bc81c2424aa607465cab94f1b0

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    غسيلwashed with saturated NaHCO3 solution (10 mL)
  2. 2
    أخرىThe organic layer was separated
  3. 3
    أخرىdried
  4. 4
    تركيزconcentrated
  5. 5
    أخرىPurification by silica gel flash column chromatography
  6. 6
    غسيلeluting with 50% ethyl acetate in hexanes
  7. 7
    أخرىafforded two fractions

الإجراء التجريبي

To a solution of 6-Bromo-1,2,3,4-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-quinolinamine (30 mg, 0.072 mmol) in dimethyl formamide (1 mL) were sequentially added 1-hydroxyazabenzotriazole (19 mg, 0.15 mmol), 1-naphthoic acid (25 mg, 0.15 mmol), diisopropylethyl amine (0.7 mL, 0.4 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (28 mg, 0.15 mmol). After 18 hours, the mixture was diluted with chloroform (10 mL) and washed with saturated NaHCO3 solution (10 mL). The organic layer was separated, dried and concentrated. Purification by silica gel flash column chromatography eluting with 50% ethyl acetate in hexanes followed by 1:9 methanol in chloroform afforded two fractions. More polar fraction 2 (14 mg) was the desired product and the less polar fraction 1 (35 mg) was diacylated product. Fraction 1 was dissolved in methanol (1 mL) and treated with NaOH solution (1 N, 0.2 mL). After 30 minutes, the mixture was concentrated and mixed with fraction 2 obtained above. The resulting mixture was dissolved in chloroform (10 mL) and washed with water (10 mL). The organic layer was dried (MgSO4), concentrated and purified by silica gel flash column eluting with 5% methanol in chloroform to afford the free base of the title compound (20 mg, 60%). The solid was dissolved in chloroform and HCl gas was bubbled for 30 seconds. The mixture was then concentrated in vacuo to afford the title compund (23 mg). MS: (M+H)+=461, 463 (1:1 ratio), 1 Br pattern.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US06602883B1uspto-grants-2003_08