Diisopropylethylamine → (S)-ethyl 1-((S)-2-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-2-(tetrahydro-2H-pyran-4-yl)acetyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acid	HCID 7009590	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	(S)-ethyl 1-((S)-2-amino-2-(tetrahydro-2H-pyran-4-yl)acetyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate	HCID 131735272	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(S)-ethyl 1-((S)-2-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-2-(tetrahydro-2H-pyran-4-yl)acetyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate	HCID 131735273	86.3%

Reaction Steps

In a 100 mL round-bottomed flask, (S)-2-(tert-butoxycarbonyl(methyl)amino)propanoic acid (128 mg, 630 μmol, Eq: 1.5), (S)-ethyl 1-((S)-2-amino-2-(tetrahydro-2H-pyran-4-yl)acetyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (140 mg, 420 μmol, Eq: 1.00) and HATU (240 mg, 630 μmol, Eq: 1.5) were combined with DMF (2 mL) to give a light yellow solution. Diisopropylethylamine (110 μL, 630 μmol, Eq: 1.5) was added and the reaction was stirred at rt over the weekend. The reaction mixture was partitioned between EtOAc and water and the separated organic layer was washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 0% to 40% EtOAc in hexanes) to give (S)-ethyl 1-((S)-2-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-2-(tetrahydro-2H-pyran-4-yl)acetyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (188 mg), m/z=519 (M+H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09309248B2
Source dataset	uspto-grants-2016_04
ORD ID	ord-8340bfcf9fb542759567f197b5bfd328
Source note	uspto-grants-2016_04