Benzylamine → N,N'-Dicyclohexylurea

Fmoc-arginine(PMC)—OH AA3 (3.83 g, 5.0 mmol) and HOBT (0.76 g, 5.0 mmol) were combined in acetonitrile (100 mL) and benzylamine (0.54 g, 5.0 mmol) was added dropwise at about rt, followed by DCC (2.06 g, 10.0 mmol) and stirred for about 16 h. A solid was filtered and the filtrate was evaporated in vacuo to an oil, which was then dissolved in ethyl acetate (100 mL) and washed with saturated NaHCO3 (2×), brine (2×), then dried (Na2SO4) and evaporated in vacuo to a solid, which was triturated with hexane (2×) to give a solid (impure with dicyclohexylurea). A portion of this solid (1.17 g, 1.25 mmol) was dissolved in acetonitrile (30 mL), diethyl amine (1.5 mL) was added and the reaction was stirred at about rt for about 1 h. The solution was then evaporated in vacuo to a solid, which was triturated with hexane (2×). The solution was then evaporated in vacuo to a solid, which was then combined in ACN (25 mL) with Fmoc-3,4difluorophenylalanine (0.53 g, 1.25 mmol) and HOBT (0.19 g, 1.25 mmol). DIC (0.32 g, 2.5 mmol) was added and the reaction was stirred at about rt for about 16 h. Fmoc-protected dipeptide was filtered (0.77 g) and stirred in ACN (30 mL) with diethyl amine (1.5 mL) for about 2.5 h. The reaction was evaporated in vacuo to an oil, which was triturated with hexane (3×) to the white solid AA4.

1. filtrationA solid was filtered
2. customthe filtrate was evaporated in vacuo to an oil, which
3. dissolutionwas then dissolved in ethyl acetate (100 mL)
4. washwashed with saturated NaHCO3 (2×), brine (2×)
5. dry with materialdried (Na2SO4)
6. customevaporated in vacuo to a solid, which
7. customwas triturated with hexane (2×)

ORD-Eintrag

ord-c8850f81b56d4459b3d879b72986bc97

Quelldatensatz

uspto-grants-2005_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06858577B1