反应详情

温度

-15 °C

A solution of ethyl 1-(4-{[1-methyl-3-({[(1-methylethyl)oxy]carbonyl}amino)-3-oxopropyl]amino}phenyl)-1H-imidazole-4-carboxylate (for a preparation see intermediate 84) (5 g, 12.4 mmol) in ethanol (80 mL) was cooled to −15° C. The solution was treated with sodium borohydride (423 mg, 11.2 mmol) followed by a solution of magnesium chloride (2.78 g, 13.7 mmol) in water (15 mL) maintaining the temperature below −10° C. The mixture was stirred below 0° C. for 1 h then at room temperature for 1 h. The suspension formed was poured onto a stirred mixture of citric acid (4.89 g, 25.5 mmol), HCl (1M in water, 130 mL) and DCM (65 mL). The resulting mixture was stirred vigorously for 30 min and the layers were separated. The aqueous phase was basified by the addition of solid K2CO3 (CARE: gas evolved) and extracted with AcOEt (4×70 mL). The combined organic phases were washed with water then brine, dried over MgSO4 and concentrated in vacuo to give ethyl 1-[(cis)-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-imidazole-4-carboxylate (3.6 g, 9.32 mmol, 75%) as a colourless foam which was used in the next step without further purification.

1. temperaturemaintaining the temperature below −10° C
2. waitat room temperature for 1 h
3. customThe suspension formed
4. stirringThe resulting mixture was stirred vigorously for 30 min
5. customthe layers were separated
6. additionThe aqueous phase was basified by the addition of solid K2CO3 (CARE: gas evolved)
7. extractionextracted with AcOEt (4×70 mL)
8. washThe combined organic phases were washed with water
9. dry with materialbrine, dried over MgSO4
10. concentrationconcentrated in vacuo