Sodium Iodide → HCID 15983453, compound

HRID 2220489Notes

Reaction equation

HRID 2220489 reaction equation
[CH3:1][N:2]1[CH2:11][CH:10](C2C=CC=CC=2)[C:9]2[C:4](=CC(=O)NC=2)[CH2:3]1.[CH3:19][O:20][C:21]1[CH:30]=[C:29]2[C:24]([CH:25]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:26][N:27]([CH3:31])[CH2:28]2)=[CH:23][N:22]=1.[CH3:38][Si](Cl)(C)C.[Na+].[I-]>CC#N>[CH3:31][N:27]1[CH2:26][CH:25]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:24]2[C:29](=[CH:30][C:21]([O:20][CH2:19][CH2:38][CH2:1][N:2]3[CH2:11][CH2:10][CH2:9][CH2:4][CH2:3]3)=[N:22][CH:23]=2)[CH2:28]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 58771900HCID 58771900, compoundHCID 69161863HCID 69161863, compound

Product 1

HCID 15983453HCID 15983453, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

6-Methyl-8-phenyl-5,6,7,8-tetrahydro-2H-[2,6]naphthyridin-3-one. A 0° C. solution of 7-methoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydro-[2,6]naphthyridine (74.5 mg, 0.293 mmol) in CH3CN (1 mL) was treated with TMSCl (1 mL) and NaI (˜10 mg). The resulting mixture was stirred at 0° C. for 30 min, then at 50° C. for 18 h. The mixture was concentrated, diluted with satd. aq. NaHCO3 and extracted with DCM. The organic layer was dried and concentrated. 1H NMR indicated ˜30% conversion to the desired product. The material was diluted with CH3CN (2 mL), treated with TMSCl (1 mL) and NaI (˜10 mg) and heated at 60° C. for 18 h. The mixture was concentrated, neutralized with satd. aq. NaHCO3 and extracted with DCM. The organic layer was dried and concentrated. The crude mixture was chromatographed (SiO2; 1-10% 2 M NH3 in MeOH/DCM) to give the title compound (29.6 mg, 42%). 1H NMR (CDCl3): 7.33-7.23 (m, 3H), 7.20-7.16 (m, 2H), 6.83 (s, 1H), 6.26 (s, 1H), 4.06-4.00 (m, 1H), 3.73 (d, J=15.9, 1H), 3.40 (d, J=15.2, 1H), 3.03-2.97 (m, 1H), 2.46 (dd, J=11.6, 10.0, 1H), 2.41 (s, 3H).

Workup

  1. waitat 50° C. for 18 h
  2. concentrationThe mixture was concentrated
  3. additiondiluted with satd
  4. extractionaq. NaHCO3 and extracted with DCM
  5. customThe organic layer was dried
  6. concentrationconcentrated
  7. additionThe material was diluted with CH3CN (2 mL)
  8. additiontreated with TMSCl (1 mL) and NaI (˜10 mg)
  9. temperatureheated at 60° C. for 18 h
  10. concentrationThe mixture was concentrated
  11. extractionaq. NaHCO3 and extracted with DCM
  12. customThe organic layer was dried
  13. concentrationconcentrated
  14. customThe crude mixture was chromatographed (SiO2; 1-10% 2 M NH3 in MeOH/DCM)

Sources & evidence

ORD record
ord-70ec0f6e3ead430bb25e5024d33c9fb6
Source dataset
uspto-grants-2008_08
Patent number
US07417054B2

Reaction notes

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