Reaction #534174

Reaction equation

HATU

Boc-N(Me)Ala-OH

58

{2-[4-(2-Amino-3,3-dimethyl-butyryl)-3-(naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethyl}-carbamic acid benzyl ester

NMM

→

59

Yield 75.4%

(1-{1-[4-(2-Benzyloxycarbonylamino-acetyl)-6-(naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid tert-butyl ester

Yield 75.4%

Solvents

EtOAc

NMP

NMP

Conditions

Workup

1. 1
   Washwashed successively with 1M HCl, saturated NaHCO3
2. 2
   Dryingdried over anhydrous Na2SO4
3. 3
   Filtrationfiltered
4. 4
   Concentrationconcentrated
5. 5
   OtherPurification by reverse phase HPLC (2″ Dynamax® C18, 10-70% ACN in H2O with 0.1% HOAc over 30 min)

Procedure

A solution of Boc-N(Me)Ala-OH (152 mg, 0.74 mmol) in NMP (3 mL) was cooled to 0° C. and treated with HATU (313 mg, 0.83 mmol) followed by NMM (0.15 mL). After 10 min, 58 (450 mg) in NMP (2 mL) was added. The reaction mixture was allowed to warm to ambient temperature overnight. The solution was diluted with EtOAc, washed successively with 1M HCl, saturated NaHCO3, dried over anhydrous Na2SO4, filtered and concentrated. Purification by reverse phase HPLC (2″ Dynamax® C18, 10-70% ACN in H2O with 0.1% HOAc over 30 min) afforded 59 as a white solid (430 mg). Mass spectrum, m/z [771.3] (M+H)+.

Source