Piperidine → 1-[(2S)-2-Amino-3-methyl-1-oxobutyl]-N-ethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxamide

HRID 627032Notes

Reaction equation

HRID 627032 reaction equation
[CH2:1]([NH:3][C:4]([CH:6]1[N:14]([C:15](=[O:38])[C@@H:16]([NH:20]C(=O)OCC2C3C=CC=CC=3C3C2=CC=CC=3)[CH:17]([CH3:19])[CH3:18])[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[CH2:7]1)=[O:5])[CH3:2].N1CCCCC1>C(#N)C>[NH2:20][C@@H:16]([CH:17]([CH3:18])[CH3:19])[C:15]([N:14]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[CH2:7][CH:6]1[C:4]([NH:3][CH2:1][CH3:2])=[O:5])=[O:38]

Participants

4

Reactant 2

HCID 8082PiperidineHCID 131735256HCID 131735256, compound

Product 1

HCID 1178731111-[(2S)-2-Amino-3-methyl-1-oxobutyl]-N-ethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxamideYield 80.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (9H-fluoren-9-yl)methyl (2S)-1-(2-(ethylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (85 mg, 166 μmol, Eq: 1.00) in acetonitrile (4 mL) was added piperidine (0.1 mL, 1.01 mmol, Eq: 6.09) and the resulting solution was stirred at rt for 1 h. The reaction mixture was concentrated in vacuo and the residue was treated with saturated aqueous NaHCO3. The aqueous layer was extracted with DCM/EtOAc (˜1:10) and the combined organic layers were concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 0% to 10% MeOH in DCM) to give 1-((S)-2-amino-3-methylbutanoyl)-N-ethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxamide (39 mg), m/z=291 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionthe residue was treated with saturated aqueous NaHCO3
  3. extractionThe aqueous layer was extracted with DCM/EtOAc (˜1:10)
  4. concentrationthe combined organic layers were concentrated in vacuo
  5. customThe crude material was purified by flash chromatography (silica gel, 12 g, 0% to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-d749eb87d4f54d77bb12e0a0319f0bcd
Source dataset
uspto-grants-2016_04
Patent number
US09309248B2

Reaction notes

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