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

HRID 627013Notes

Reaction equation

HRID 627013 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+].Cl.[CH2:22]([NH2:24])[CH3:23].CN(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(OCC)(=O)C.C([O-])(O)=O.[Na+]>[CH2:22]([NH:24][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])[CH3:23]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 11198Ethylamine hydrochlorideHCID 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 118380480tert-butyl 2-(ethylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylateYield 74.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

In a 100 mL round-bottomed flask, lithium 1-(tert-butoxycarbonyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (400 mg, 1.48 mmol, Eq: 1.00), ethanamine hydrochloride (145 mg, 1.78 mmol, Eq: 1.2) and HATU (675 mg, 1.78 mmol, Eq: 1.2) were combined in DMF (6 mL) to give a light yellow suspension. Triethylamine (0.45 mL, 3.2 mmol, Eq: 2.2) was added. The reaction was stirred overnight then diluted with ethyl acetate (30 mL) and saturated aqueous NaHCO3 (20 mL). The aqueous layer was separated, extracted with DCM (20 mL×2) and the combined organic layers were washed with 1 M aqueous NaOH (10 mL), dried over Na2SO4 and concentrated in vacuo. The residue was azeotroped with n-heptane (30 mL×3) to give tert-butyl 2-(ethylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (322 mg), m/z=292 (M+H).

Workup

  1. customto give a light yellow suspension
  2. customThe aqueous layer was separated
  3. extractionextracted with DCM (20 mL×2)
  4. washthe combined organic layers were washed with 1 M aqueous NaOH (10 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was azeotroped with n-heptane (30 mL×3)

Sources & evidence

ORD record
ord-9e291fbc534e42889b584edc263747cd
Source dataset
uspto-grants-2016_04
Patent number
US09309248B2

Reaction notes

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