Piperidine → L-Glutamic Acid

Approximately 10 mg of Fmoc-Glu-Fib-Trityl-chloride resin was treated with 20% (v/v) piperidine in DMF (2 mL×1 min, filtered, then 2 mL×5 min), filtered and washed (NMP). Compound (42f) (10 eqv to Glu-Fib amount on the resin) was activated with HATU (P/N: Applied Biosystems 4317033, 9.5 eqv) and N,N-Diisopropylethylamine (30 eqv) in NMP (˜1 mL), added to the resin and mixed for 30 min. Resin was then filtered, washed with NMP, and Fmoc group was cleaved. Piperazine acetic acid-TFA salt (10 eqv) was then activated using HATU (9.5 eqv) and N,N-Diisopropylethylamine (60 eqv) in NMP (˜1.5 mL) and added to the resin. After 30 min the resin was washed with NMP followed by CH3CN. Conjugated peptide was cleaved (and deprotected) from the resin using 95:5 TFA-water (200 μL, 2 h) and precipitated using Et2O. Analysis of compound (42) was performed using ES-MS (direct infusion in water, Calculated [M+H]+=1923.8, Observed [M+H]+=1924.0)

1. filtrationfiltered
2. filtration2 mL×5 min), filtered
3. washwashed (NMP)
4. additionadded to the resin
5. additionmixed for 30 min
6. filtrationResin was then filtered
7. washwashed with NMP, and Fmoc group
8. additionadded to the resin
9. washAfter 30 min the resin was washed with NMP
10. custom95:5 TFA-water (200 μL, 2 h)
11. customprecipitated

ORD record

ord-51c0bbff5b9d48f89952d647a343f66e

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501498B2