Reaction #714205

Reaction equation

Diisopropylethylamine

(S)-ethyl 1-((S)-2-amino-3-methylbutanoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate hydrochloride

(S)-2-(tert-butoxycarbonyl(methyl)amino)propanoic acid

HATU

→

(S)-ethyl 1-((S)-2-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-3-methylbutanoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate

Yield 81.7%

Solvents

—

hexanes

EtOAc

DMF

Conditions

Workup

1. 1
   Washwashed with 0.1 M aqueous KHSO4, 0.1 M aqueous NaOH, and brine
2. 2
   Concentrationconcentrated in vacuo
3. 3
   OtherThe crude material was purified by flash chromatography (silica gel, 80 g, 0% to 20% EtOAc/DCM:hexanes 1:1)
4. 4
   Wash20% to 40% EtOAc/DCM:hexanes 1:1) after first spot has eluted)

Procedure

To a solution of (S)-ethyl 1-((S)-2-amino-3-methylbutanoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate hydrochloride (1.6 g, 4.88 mmol, Eq: 1.00) in DMF (20 mL) was added (S)-2-(tert-butoxycarbonyl(methyl)amino)propanoic acid (1.2 g, 5.9 mmol, Eq: 1.21) and HATU (2.2 g, 5.79 mmol, Eq: 1.19). Diisopropylethylamine (2.2 mL, 12.6 mmol, Eq: 2.58) was then added and the resulting yellow solution was stirred at rt for 1 h. The reaction mixture was diluted with EtOAc (100 mL) and hexanes (50 mL) and washed with 0.1 M aqueous KHSO4, 0.1 M aqueous NaOH, and brine and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, 0% to 20% EtOAc/DCM:hexanes 1:1) then 20% to 40% EtOAc/DCM:hexanes 1:1) after first spot has eluted) to give (S)-ethyl 1-((S)-2-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-3-methylbutanoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (eluted second 1.9 g), m/z=477 (M+H).

Source