HCID 66666120, compound → HCID 66666069, compound

HRID 406177Notes

Reaction equation

HRID 406177 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]3[C:14](=[N:15][C:16]=2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N+:13]([O-])=[CH:12][CH:11]=[CH:10]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:24]1(C2C(C3C=CC=CC=3)=CC3C(=NC=CC=3)[N+]=2[O-])C=CC=CC=1.C[Mg]Cl>C1COCC1>[CH3:24][C:12]1[N:13]=[C:14]2[C:9]([CH:8]=[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:15]2)=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 66666120HCID 66666120, compoundHCID 66666286HCID 66666286, compound2×HCID 178418332HCID 178418332, compound

Product 1

HCID 66666069HCID 66666069, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A cooled (0° C.) mixture of 6,7-diphenyl-1,8-naphthyridine 1-oxide and 2,3-diphenyl-1,8-naphthyridine 1-oxide (Intermediates C) (1 g, 3.35 mmol) in dry THF (10 ml) under an atmosphere of N2 was treated dropwise with methylmagnesium chloride (1.676 ml, 5.03 mmol). The resulting mixture was stirred at room temperature for 45 minutes and then partitioned between EtOAc and water. The aqueous portion was extracted with EtOAc (2×100 ml) and the combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The crude residue was dissolved in acetic anhydride (5 ml) and heated at 120° C. for 10 mins using microwave radiation. The resulting mixture was partitioned between DCM (150 ml) and water. The organic portion was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The crude product was loaded onto a Isolute™ SCX-2 cartridge and eluted with MeOH followed by 2M NH3 in MeOH. The methanolic ammonia fractions were concentrated in vacuo to afford a brown oil which was purified by chromatography on silica eluting with 0-50% EtOAc in iso-hexane to afford the title product;

Workup

  1. temperatureA cooled
  2. custompartitioned between EtOAc and water
  3. extractionThe aqueous portion was extracted with EtOAc (2×100 ml)
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe crude residue was dissolved in acetic anhydride (5 ml)
  9. temperatureheated at 120° C. for 10 mins
  10. customThe resulting mixture was partitioned between DCM (150 ml) and water
  11. washThe organic portion was washed with brine
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. washeluted with MeOH
  16. concentrationThe methanolic ammonia fractions were concentrated in vacuo
  17. customto afford a brown oil which
  18. customwas purified by chromatography on silica eluting with 0-50% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-3f90e044bcde49f680ec9b6fb3df75da
Source dataset
uspto-grants-2014_06
Patent number
US08754085B2

Reaction notes

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