Triethylamine → tert-butyl 2-carbamoyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

HRID 627016Notes

Reaction equation

HRID 627016 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:11]2[CH2:10][CH:9]1[C:17]([O-:19])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].C(=O)(O)[O-].[NH4+].C[N:27](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C.C([O-])(O)=O.[Na+].[OH-].[Na+]>[C:17]([CH:9]1[N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:11]2[CH2:10]1)(=[O:19])[NH2:27]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 14013Ammonium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118380491lithium 1-(tert-butoxycarbonyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate

Product 1

HCID 118380479tert-butyl 2-carbamoyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylateYield 102.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 14798Sodium HydroxideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a suspension of lithium 1-(tert-butoxycarbonyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (100 mg, 370 μmol, Eq: 1.00) in DMF (5.00 mL) was added sequentially ammonium bicarbonate (90.0 mg, 1.14 mmol, Eq: 3.08), HATU (210 mg, 552 μmol, Eq: 1.49) and triethylamine (100 μL, 717 μmol, Eq: 1.94). The resulting dark yellow mixture was stirred at rt for 2 h. The reaction mixture was diluted with saturated aqueous NaHCO3 (10 mL) and 1 M aqueous NaOH (0.5 mL) and extracted with DCM. The combined organic layers were dried (Na2SO4) and concentrated in vacuo, using n-heptane to azeotrope off residual DMF. The resulting residue was purified by flash chromatography (silica gel, 12 g, 0% to 10% MeOH in DCM) to give tert-butyl 2-carbamoyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate as a white solid (100 mg), m/z=264 (M+H).

Workup

  1. extractionextracted with DCM
  2. dry with materialThe combined organic layers were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by flash chromatography (silica gel, 12 g, 0% to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-918c9b286384419ca3f786afd28a077c
Source dataset
uspto-grants-2016_04
Patent number
US09309248B2

Reaction notes

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