Methylamine hydrochloride → HCID 59831817, compound

Temperature

5 °C

To a 5° C. stirring suspension of MeNH2.HCl (220 mg, 3.2 mmol) in benzene (3 ml) was added dropwise Me3Al (2 M in toluene, 1.6 ml, 3.2 mmol). The mixture was stirred at room temperature for 45 minutes. A solution of 3-(1H-indol-6-yl)-3-(4-methoxy-phenyl)-propionic acid methyl ester XXXIV (480 mg, 1.6 mmol) in benzene (15 ml) was added and the resulting mixture was stirred at reflux for 3 hours. The reaction mixture was cooled to room temperature and additional mixture of MeNH2.HCl (110 mg, 1.6 mmol) in benzene (1.5 ml) and Me3Al (2M in toluene, 0.8 ml, 1.6 mmol) was added. The resulting mixture was stirred at reflux for 1.5 hours, cooled to room temperature, and the reaction was quenched by slow addition of HCl (1M, 35 ml). The mixture was stirred vigorously for 5 minutes and extracted with EtOAc (50 ml). The combined organic layers were washed with water and brine, dried over MgSO4, filtered, concentrated and purified via flash chromatography (hexane/EtOAc) to provide 3-(1H-indol-6-yl)-3-(4-methoxy-phenyl)-N-methyl-propionamide XXXV (390 mg, 81% yield) as a white solid.

1. stirringThe mixture was stirred at room temperature for 45 minutes
2. stirringthe resulting mixture was stirred
3. temperatureat reflux for 3 hours
4. temperatureThe reaction mixture was cooled to room temperature
5. additionwas added
6. stirringThe resulting mixture was stirred
7. temperatureat reflux for 1.5 hours
8. temperaturecooled to room temperature
9. customthe reaction was quenched by slow addition of HCl (1M, 35 ml)
10. stirringThe mixture was stirred vigorously for 5 minutes
11. extractionextracted with EtOAc (50 ml)
12. washThe combined organic layers were washed with water and brine
13. dry with materialdried over MgSO4
14. filtrationfiltered
15. concentrationconcentrated
16. custompurified via flash chromatography (hexane/EtOAc)

ORD record

ord-0679052d49cd457084d84a1836d3150e

Source dataset

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07803830B2