Ethylenediamine → 1H-Spiro[[1,8]naphthyridine-4,4'-piperidin]-2(3H)-one

HRID 550400Notes

Reaction equation

HRID 550400 reaction equation
[O:1]=[C:2]1[CH2:26][C:10]2([CH:15]=[CH:14][N:13](C(OCC3C=CC=CC=3)=O)[CH2:12][CH2:11]2)[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]1COCC[Si](C)(C)C.FC(F)(F)C(O)=O.C(N)CN>ClCCl>[NH:13]1[CH2:12][CH2:11][C:10]2([C:9]3[C:4](=[N:5][CH:6]=[CH:7][CH:8]=3)[NH:3][C:2](=[O:1])[CH2:26]2)[CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 57663850benzyl 2-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-2,2',3,3'-tetrahydro-1H,1'H-spiro[1,8-naphthyridine-4,4'-pyridine]-1'-carboxylate

Product 1

HCID 591657751H-Spiro[[1,8]naphthyridine-4,4'-piperidin]-2(3H)-oneYield 74.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of benzyl 2-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-2,2′,3,3′-tetrahydro-1H,1′H-spiro[1,8-naphthyridine-4,4′-pyridine]-1′-carboxylate (384 mg, 0.800 mmol) in dichloromethane (10 mL) was added trifluoroacetic acid (10 mL). After 3 h, the reaction was concentrated, diluted with dichloromethane (10 mL) and ethylenediamine (720 mg, 12.0 mmol) was added. After 18 h, the reaction was concentrated, the residue partitioned between saturated aqueous NaHCO3 and dichloromethane, and the layers separated. The aqueous phase was extracted with further portions of dichloromethane (2×), the organic layers combined, dried, and concentrated. 10% Palladium on carbon (300 mg) was added to a solution of this material in EtOH (10 mL). The reaction vessel was evacuated and back-filled with nitrogen (3×), then back-filled with hydrogen (1 atm). After 24 h, the mixture was filtered though celite and concentrated to give the title compound (130 mg). MS: m/z=218.1 (M+1). 1H NMR (500 MHz, CD3OD) δ 8.14 (dd, J=1.6, 5.0 Hz, 1H), 7.80 (dd, J=1.6, 7.7 Hz, 1H), 7.10 (dd, J=5.0, 7.7 Hz, 1H), 2.98-2.95 (m, 4H), 2.78 (s, 2H), 1.96-1.90 (m, 2H), 1.69 (brd, J=11.5 Hz, 2H).

Workup

  1. concentrationthe reaction was concentrated
  2. additionwas added
  3. waitAfter 18 h
  4. concentrationthe reaction was concentrated
  5. customthe residue partitioned between saturated aqueous NaHCO3 and dichloromethane
  6. customthe layers separated
  7. extractionThe aqueous phase was extracted with further portions of dichloromethane (2×)
  8. customdried
  9. concentrationconcentrated
  10. addition10% Palladium on carbon (300 mg) was added to a solution of this material in EtOH (10 mL)
  11. customThe reaction vessel was evacuated
  12. additionback-filled with nitrogen (3×)
  13. additionback-filled with hydrogen (1 atm)
  14. waitAfter 24 h
  15. filtrationthe mixture was filtered though celite and
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-6ed7b62489d84f9581da83435fa4d632
Source dataset
uspto-grants-2011_05
Patent number
US07947678B2

Reaction notes

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