Water → tert-Butyl 8-methyl-2-oxo-1,5,7,8-tetrahydro-1,6-naphthyridine-6(2H)-carboxylate

HRID 2200067Notes

Reaction equation

HRID 2200067 reaction equation
[CH3:1][CH:2]1[C:7](=O)[CH2:6][CH2:5][N:4]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:3]1.N1CCCC1.O.[C:22]([NH2:26])(=[O:25])[C:23]#[CH:24]>C1(C)C=CC=CC=1>[CH3:1][CH:2]1[C:7]2[NH:26][C:22](=[O:25])[CH:23]=[CH:24][C:6]=2[CH2:5][N:4]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 31268PyrrolidineHCID 101445PropynamideHCID 22644642tert-Butyl 3-methyl-4-oxopiperidine-1-carboxylate

Product 1

HCID 68313489tert-Butyl 8-methyl-2-oxo-1,5,7,8-tetrahydro-1,6-naphthyridine-6(2H)-carboxylateYield 55%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

tert-Butyl 3-methyl-4-oxopiperidine-1-carboxylate (commercially available from Ryan Scientific, Mt. Pleasant, S.C.)(1.7 g, 7.97 mmol) and pyrrolidine (1.3 mL, 15.94 mmol) were dissolved in toluene (9 mL), and the solution was heated under reflux, with the removal of water under Dean-Stark conditions, for 5 hours. The solution was then cooled to room temperature and propiolamide (prepared as described in EP 1813606)(1.1 g, 15.94 mmol) was added. The reaction mixture thus obtained was heated overnight under reflux. The reaction mixture was concentrated, and the residue was purified by flash chromatography on silica gel eluting with 0% to 10% MeOH in DCM to give the title compound (2.1 g, 55% yield). 1H NMR (400 MHz, CDCl3) δ ppm 1.36 (3H, d, J=7.04 Hz), 1.52 (9H, s), 3.37-3.44 (1H, m), 3.77-3.84 (1H, m), 4.12-4.17 (1H, m), 6.48 (1H, d, J=9.39 Hz), 7.21 (1H, d, J=9.39 Hz) ppm; LC/MS m/z: 265 (M+1).

Workup

  1. temperaturethe solution was heated
  2. customThe reaction mixture thus obtained
  3. temperaturewas heated overnight
  4. temperatureunder reflux
  5. concentrationThe reaction mixture was concentrated
  6. customthe residue was purified by flash chromatography on silica gel eluting with 0% to 10% MeOH in DCM

Sources & evidence

ORD record
ord-d1a9680a22134f5ab30463848a711d1e
Source dataset
uspto-grants-2016_06
Patent number
US09359355B2

Reaction notes

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