반응 #52120

반응 방정식

TBTU

HCl

D-Alanine-tert-butyl ester hydrochloride

DIPEA

(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

(S)—-[(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 tert-butyl ester

→

title compound

수율 44.0%

(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-α]imidazole-3-sulfonyl]-pyrrolidine-2-carbonyl)-amino)-propionic acid

수율 44.0%

용매

DMF CH2Cl2

CH2Cl2

반응 조건

후처리

1. 1
   workup.ADDITIONwas then added
2. 2
   추출extracted with CH2Cl2
3. 3
   세척The organic layers were washed with saturated aqueous NaHCO3
4. 4
   건조The combined organic phase was dried (MgSO4)
5. 5
   여과filtered
6. 6
   농축concentrated
7. 7
   workup.DISSOLUTIONThe resultant residue was re-dissolved
8. 8
   workup.DISSOLUTIONdissolved in either 50% trifluoroacetic acid—CH2Cl2 or 4N HCl-dioxane (5 mL)
9. 9
   workup.STIRRINGstirred at room temperature for 2 h
10. 10
    기타Following aqueous workup the residue was purified by silica gel chromatography

실험 절차

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).

출처