Trifluoroacetic acid → HCID 58979055, compound

Temperature

45 °C

General Parallel Synthesis Procedure: 2-{2-Aminomethyl-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenoxy}-2-methyl-propionic acid ethyl ester: trifluoroacetic acid salt (381 mg, 0.650 mmol max.) was dissolved in CH2Cl2 (25 mL) and washed with saturated NaHCO3 solution (15 mL). The organic layer was dried (NaSO4), filtered, and concentrated to 2-{2-aminomethyl-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenoxy}-2-methyl-propionic acid ethyl ester (245 mg, 0.59 mmol, 86%). A portion of this free base (13 mg, 0.030 mmol) in CH2Cl2 (0.8 mL) was treated with triethylamine (0.050 mL, 0.36 mmol) then ethyl chloroformate (0.020 mL, 0.21 mmol). The reaction mixture was shaken overnight and dimethylethylenediamine (0.050 mL, 0.47 mmol) was added. The reaction mixture was shaken for 2 h, diluted with MeOH (0.5 mL), and passed through an SCX column (1 g, equilibrated with 4 mL MeOH/CH2Cl2 1/1). The methyl ester-amide product was eluted with MeOH/CH2Cl2 (1:1, 8 mL) and concentrated. The residue was dissolved in THF (1 mL) and EtOH (1 mL) and treated with 2N NaOH (0.5 mL). The solution was heated at 45° C. for 45 min, cooled, concentrated, and acidified with 1N HCl (2.5 mL). The mixture was diluted with diluted with CH2Cl2 (0.5 mL), transferred to a 3-mL ChemElute cartridge, and eluted with CH2Cl2 (8 mL). The solvent was removed under a stream of N2. The crude product was dried under vacuum and purified by mass-directed HPLC to give a foam (2.7 mg, 19%). %). MS (ES+) m/z 483.5 [M+H]+.

1. customGeneral Parallel Synthesis Procedure
2. washwashed with saturated NaHCO3 solution (15 mL)
3. dry with materialThe organic layer was dried (NaSO4)
4. filtrationfiltered
5. stirringThe reaction mixture was shaken for 2 h
6. washThe methyl ester-amide product was eluted with MeOH/CH2Cl2 (1:1, 8 mL)
7. concentrationconcentrated
8. dissolutionThe residue was dissolved in THF (1 mL)
9. additionEtOH (1 mL) and treated with 2N NaOH (0.5 mL)
10. temperaturecooled
11. concentrationconcentrated
12. additionThe mixture was diluted
13. additionwith diluted with CH2Cl2 (0.5 mL)
14. washeluted with CH2Cl2 (8 mL)
15. customThe solvent was removed under a stream of N2
16. dry with materialThe crude product was dried under vacuum
17. custompurified by mass-directed HPLC

ORD record

ord-e5ee13a8d4df4ee1acfd7cf8598652a9

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07282501B2