反应详情

温度

80 °C

To a suspension of (2-aminothiazol-5-yl)methanol (35 mg, 0.269 mmol) and L-Tyrosine (199.6 mg, 1.102 mmol) in nitromethane (3.00 mL) is added trifluoromethanesulfonic acid (170 μL, 1.914 mmol). The resulting solution is sonicated for 15 sec, then heated at 80° C. for 18 h. The reaction is evaporated to dryness and the residue is purified by preparative HPLC (Condition A) using a PHENOMENEX® Luna Axia 30×100 mm S10 column from 0% Solvent B to 60% Solvent B over 12 min, ret. T=5.14 min. The product fractions are poured thru a washed WATERS OASIS® MCX 20 cc (1 g) LP extraction cartridge and washed with additional MeOH (50 mL). Elution with Aldrich 2.0M NH3/MeOH (20 mL) followed by evaporation gives 48.7 mg (55.6%) of the title compound as a light tan solid. LC/MS (Condition A): ret. T=0.63 min, (M+H)+ 294.05. Analytical HPLC: (Condition C): >95%, ret. T=3.26 min, (Condition D): >90%, ret. T=3.00 min. 1H NMR (500 MHz, DMSO-d6+D2O) δ ppm 6.86-7.04 (2 H, m), 6.67-6.76 (1 H, m), 6.58-6.67 (1 H, m), 3.74 (2 H, br. s.), 3.33 (1 H, br. s.), 3.02 (1 H, d, f=10.07 Hz), 2.68 (1 H, br. s.).

1. customThe resulting solution is sonicated for 15 sec
2. customThe reaction is evaporated to dryness
3. customthe residue is purified by preparative HPLC (Condition A)
4. customover 12 min
5. customT=5.14 min
6. additionThe product fractions are poured thru
7. extractiona washed WATERS OASIS® MCX 20 cc (1 g) LP extraction cartridge
8. washwashed with additional MeOH (50 mL)
9. washElution with Aldrich 2.0M NH3/MeOH (20 mL)
10. customfollowed by evaporation