Hydrochloric Acid → (R)-2-({(S)-1-[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-pyrimidin-5-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carbonyl}-amino)-propionic acid

TBTU (0.078 g) and (S)-1-[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-pyrimidin-5-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-α]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (Example 14) (0.10 g) were combined in 7% DMF-CH2Cl2 (3.2 mL) at room temperature. D-Alanine-tert-butyl ester hydrochloride (0.044 g), followed by DIPEA (0.07 mL), was then added and the reaction solution was stirred for 16 h. The reaction was diluted with CH2Cl2, poured into 1N HCl, and extracted with CH2Cl2. The organic layers were washed with saturated aqueous NaHCO3 followed by H2O. The combined organic phase was dried (MgSO4), filtered and concentrated. The resultant residue was re-dissolved dissolved in either 50% trifluoroacetic acid—CH2Cl2 or 4N HCl-dioxane (5 mL) and stirred at room temperature for 2 h. Following aqueous workup the residue was purified by silica gel chromatography to afford the title compound (0.045 g) as a foam (698.9, M+1).

1. additionwas then added
2. extractionextracted with CH2Cl2
3. washThe organic layers were washed with saturated aqueous NaHCO3
4. dry with materialThe combined organic phase was dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe resultant residue was re-dissolved
8. dissolutiondissolved in either 50% trifluoroacetic acid—CH2Cl2 or 4N HCl-dioxane (5 mL)
9. stirringstirred at room temperature for 2 h
10. customFollowing aqueous workup the residue was purified by silica gel chromatography

ORDレコード

ord-907e80d63710403bbfab57a49ec0d380

出典データセット

uspto-grants-2005_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06852748B1