Diisopropylethylamine → 1-[2-(S)-amino-3-thiophen-2-yl-propionyl]-4-biphenyl-4-ylmethyl-piperidine-4-carboxylic acid(tetrahydro-pyran-4-ylmethyl)-amide

To a solution of 4-biphenyl-4-ylmethyl-1-[2-(S)-tert-butoxycarbonylamino-3-thiophen-2-yl-propionyl]-piperidine-4-carboxylic acid (0.24 mmol; 0.13 g) in DMF (5 mL) was added C-(tetrahydro-pyran-4-yl)-methylamine (0.28 mmol; 0.027 g), N,N-diisopropyl-N-ethylamine (0.48 mmol; 0.084 mL) and HBTU (0.28 mmol; 0.108 g), and the resulting mixture was stirred at room temperature overnight. The resulting mixture was then purified via reverse phase HPLC and the desired fractions were combined and lyophilized. The resulting residue was dissolved in THF (5 mL) and a 4N HCl solution in 1,4-dioxane (15 mL) was added. The resulting solution was stirred for 7 hours at room temperature and evaporated. The residue was triturated with diethyl ether and dried under vacuum to yield 1-[2-(S)-amino-3-thiophen-2-yl-propionyl]-4-biphenyl-4-ylmethyl-piperidine-4-carboxylic acid(tetrahydro-pyran-4-ylmethyl)-amide as a hydrochloride salt.

1. customThe resulting mixture was then purified via reverse phase HPLC
2. dissolutionThe resulting residue was dissolved in THF (5 mL)
3. additiona 4N HCl solution in 1,4-dioxane (15 mL) was added
4. stirringThe resulting solution was stirred for 7 hours at room temperature
5. customevaporated
6. customThe residue was triturated with diethyl ether
7. customdried under vacuum

ORD-Eintrag

ord-49d7f68a454344bdb0405c8d37e53f3d

Quelldatensatz

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08686152B2