Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → tert-Butyl 1-[3-({(3R)-N-[(allyloxy)carbonyl]-4,4,4-trifluorovalyl}amino)-4-chlorobenzyl]cyclopropanecarboxylate

Participants

Reaction Steps

398.5 mg (1.56 mmol) of (3R)—N-[(allyloxy)carbonyl]-4,4,4-trifluorovaline (diastereomer mixture) and 400 mg (1.42 mmol) of tert-butyl 1-(3-amino-4-chlorobenzyl)cyclopropanecarboxylate were dissolved in a mixture of 4.7 ml of DMF and 1.6 ml of pyridine, and 647.8 mg (1.70 mmol) of HATU were added at RT. The reaction mixture was stirred at RT overnight. A further 400 mg (1.42 mmol) of tert-butyl 1-(3-amino-4-chlorobenzyl)cyclopropanecarboxylate and 647.8 mg (1.70 mmol) of HATU were added, and the reaction mixture was stirred at 50° C. for another 4 h. After dilution with ethyl acetate, the mixture was washed successively with sat. sodium bicarbonate solution, 1 N hydrochloric acid and sat. sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water). This gave 453 mg of the target product (55.9% of theory, diastereomer ratio >8:1).

Provenance & Evidence