Boc-D-phenylalanine → 3(R,S)-[2(R)-(tert-Butyloxycarbonvl)amino-3-phenylpropionylamino]-5-cyclohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

To a solution of 3(R,S)-amino-5-cyclohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (4 g) in anhydrous dimethylformamide (35 ml), under an atmosphere of nitrogen, was added in succession Boc-D-phenyl-alanine (4.11 g), 1-hydroxybenzotriazole trihydrate (2.09 g) and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride (2.97 g). Triethylamine (2.16 ml) was then added and the resulting suspension was stirred at ambient temperature for 20 min. The solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate (50 ml) and 10% citric add solution (50 ml). The organic phase was separated and the aqueous phase extracted with ethyl acetate (3×50 ml). The combined organic phases were washed with 10% sodium hydroxide solution (50ml), water (50 ml) and brine (50 ml), dried (MgSO4) and evaporated in vacuo. The residue was chromatographed on silica gel, using 1:1 petrol:ethyl acetate as the eluant, to afford the product (7.26 g), mp 95°-98° C. 1H NMR (360 MHz, CDCl3) δ 0.99-1.11 (1H, m), 1.16-1.72 (7H, m), 1.40 (9H, s), 1.83-1.92 (1H, m), 1.98-2.06(1H, m), 2.73-2.83 (1H, m), 3.10-3.24) (2H, m), 3.38 (3H, s), 4.53 (1H, brs), 4.98 (1H, brs), 5.28-5.34 (2H, m), 7.19-7.32 (7H, m), 7.49-7.58 (2H, m).

1. customThe solvent was removed under reduced pressure
2. customthe residue was partitioned between ethyl acetate (50 ml) and 10% citric add solution (50 ml)
3. customThe organic phase was separated
4. extractionthe aqueous phase extracted with ethyl acetate (3×50 ml)
5. washThe combined organic phases were washed with 10% sodium hydroxide solution (50ml), water (50 ml) and brine (50 ml)
6. dry with materialdried (MgSO4)
7. customevaporated in vacuo
8. customThe residue was chromatographed on silica gel

ORDレコード

ord-6798e71983b24046b5974ba57b835432

出典データセット

uspto-grants-1996_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05556969