تفاعل #52120

معادلة التفاعل

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

المردود 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

المردود 44.0%

المذيبات

DMF CH2Cl2

CH2Cl2

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONwas then added
2. 2
   استخلاصextracted with CH2Cl2
3. 3
   غسيلThe organic layers were washed with saturated aqueous NaHCO3
4. 4
   تجفيفThe combined organic phase was dried (MgSO4)
5. 5
   ترشيحfiltered
6. 6
   تركيزconcentrated
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
    أخرىFollowing aqueous workup the residue was purified by silica gel chromatography

الإجراء التجريبي

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).

المصدر