Sodium hydride → Ammonia

HRID 2220490Notes

Reaction equation

HRID 2220490 reaction equation
[CH3:1][N:2]1[CH2:11][CH:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:9]2[C:4](=[CH:5][C:6](=[O:18])[NH:7][CH:8]=2)[CH2:3]1.[H-].[Na+].Cl[CH2:22][CH2:23][CH2:24]I>CN(C=O)C.C1COCC1>[NH3:2].[CH3:1][N:2]1[CH2:11][CH:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:9]2[C:4](=[CH:5][C:6]([O:18][CH2:22][CH2:23][CH2:24][N:2]3[CH2:11][CH2:10][CH2:9][CH2:4][CH2:3]3)=[N:7][CH:8]=2)[CH2:3]1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 813631-Chloro-3-iodopropaneHCID 58771900HCID 58771900, compound

Product 2

HCID 222AmmoniaYield 10%HCID 15983453HCID 15983453, compoundYield 2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6-methyl-8-phenyl-5,6,7,8-tetrahydro-2H-[2,6]naphthyridin-3-one (82.8 mg, 0.326 mmol) in DMF (3 mL) and THF (2 mL) was treated with NaH (60% in oil; 62 mg). After 30 min, 1-chloro-3-iodopropane (0.075 mL) was added. After 1 h at 0° C., the mixture was diluted with satd. aq. NaHCO3 and extracted with DCM. The organic layer was washed with H2O (2×), dried, and concentrated. The residue was diluted with n-butanol (5 mL) and treated with piperidine (1.5 mL), Na2CO3 (150 mg), and KI (˜10 mg). After 18 h at 55° C., the mixture was cooled, concentrated, neutralized with satd. aq. NaHCO3, and extracted with DCM. The organic layer was dried and concentrated. Preparative TLC (SiO2; 10% 2 M NH3 in MeOH/DCM) gave the title compound (2.5 mg, 2%). 1H NMR (CDCl3): 7.34-7.19 (m, 5H), 6.84 (s, 1H), 6.31 (s, 1H), 4.05-4.00 (m, 1H), 3.88-3.82 (m, 2H), 3.66 (d, J=15.9, 1H), 3.40 (d, J=16.0, 1H), 2.99-2.93 (m, 1H), 2.46-2.40 (m, 1H), 2.39 (s, 3H), 2.55-2.06 (m, 6H), 1.87-1.74 (m, 2H), 1.46-1.33 (m, 6H). 6-Methyl-8-phenyl-2-(3-piperidin-1-yl-propyl)-5,6,7,8-tetrahydro-2H-[2,6]naphthyridin-3-one (22.6 mg, 19%) was also obtained. 1H NMR (CDCl3): 7.65 (s, 1H), 7.32-7.17 (m, 5H), 6.45 (s, 1H), 4.27-4.18 (m, 3H), 3.65 (d, J=15.7, 1H), 3.53 (d, J=15.6, 1H), 3.04-2.99 (m, 1H), 2.58-2.37 (m, 9H), 2.00-1.91 (m, 2H), 1.70-1.54 (m, 5H), 1.47-1.40 (m, 2H).

Workup

  1. waitAfter 1 h at 0° C.
  2. additionthe mixture was diluted with satd
  3. extractionaq. NaHCO3 and extracted with DCM
  4. washThe organic layer was washed with H2O (2×)
  5. customdried
  6. concentrationconcentrated
  7. additionThe residue was diluted with n-butanol (5 mL)
  8. additiontreated with piperidine (1.5 mL), Na2CO3 (150 mg), and KI (˜10 mg)
  9. waitAfter 18 h at 55° C.
  10. temperaturethe mixture was cooled
  11. concentrationconcentrated
  12. extractionaq. NaHCO3, and extracted with DCM
  13. customThe organic layer was dried
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-ad4ce5b1fada452c820b5c7fa9cd9721
Source dataset
uspto-grants-2008_08
Patent number
US07417054B2

Reaction notes

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