4-Methylmorpholine → Leucinamide

0.3 g (0.33 mmol) of N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-α-aspartyl]-O-tert-butyl-L-α-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucine was dissolved in 15 ml of dichloromethane. 0.22 ml (1.98 mmol) of N-methylmorpholine, 96 mg (0.5 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 45 mg (0.33 mmol) of hydroxybenzotriazole and 217 mg (0.99 mmol) of 3,3-difluoro-1(S)-(dimethoxymethyl)butylamine hydrochloride were added and the solution was stirred at room temperature for 18 hours. The mixture was washed with 2M hydrochloric acid and aqueous sodium hydrogen carbonate solution, dried over anhydrous sodium sulphate and evaporated. The residue was triturated with diethyl ether and the resulting solid was filtered off and dried. There were obtained 143 g of N2-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-α-aspartyl]-O-tert-butyl-L-α-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-N1-[3,3-difluoro-1(S)-dimethoxymethyl)butyl]-L-leucinamide; MS: m/e 1106 [M+Na]+.

1. washThe mixture was washed with 2M hydrochloric acid and aqueous sodium hydrogen carbonate solution
2. dry with materialdried over anhydrous sodium sulphate
3. customevaporated
4. customThe residue was triturated with diethyl ether
5. filtrationthe resulting solid was filtered off
6. customdried

ORD record

ord-c01f8b00e46648af9de8938cbc8d0c73

Source dataset

uspto-grants-2000_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06018020