Sodium Bicarbonate → HCID 58071906, compound

HRID 715723Notes

Reaction equation

HRID 715723 reaction equation
[CH2:1]([NH:4][C:5]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([O:23][CH3:24])[CH:16]=2)[CH:12]=[C:11]2[C:6]=1[CH:7]=[CH:8][CH:9]=[N:10]2)[CH:2]=[CH2:3].[C:25](=[O:28])([O-])O.[Na+].BrC(Br)=[N:32][OH:33]>C(OCC)(=O)C>[CH3:24][O:23][C:17]1[CH:16]=[C:15]([C:13]2[CH:12]=[C:11]3[C:6]([CH:7]=[CH:8][CH:9]=[N:10]3)=[C:5]([NH:4][CH2:1][CH:2]3[O:33][NH:32][C:25](=[O:28])[CH2:3]3)[N:14]=2)[CH:20]=[CH:19][C:18]=1[O:21][CH3:22]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 27632191-bromo-N-hydroxymethanecarbonimidoyl bromideHCID 58071944HCID 58071944, compound

Product 1

HCID 58071906HCID 58071906, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

0.233 g Allyl-[7-(3,4,dimethoxy-phenyl)-[1,6]-naphthyridin-5-yl]-amine (I.35) were placed in 2.9 mL ethyl acetate at ambient temperature, then 0.265 g sodium hydrogen carbonate and 0.220 g dibromoformaldoxime were added. The reaction was stirred at ambient temperature for 21 h. After this time the reaction was poured onto water and extracted with ethyl acetate (×2). The combined organic fractions were dried with sodium sulfate and the solvent was removed from the filtrate under reduced pressure to provide 1.36 as a mixture of enantiomers which was used without further purification. The crude material was placed in 6 mL tetrahydrofuran at ambient temperature, then 23.9 mL of 1M sodium hydroxide and 23.8 mg tetrabutylammonium hydrogensulfate were added. The reaction was heated to 80° C. where it was maintained for 22 h. After this time, reaction mixture was cooled to ambient temperature and washed with diethyl ether (×2). The aqueous phase was acidified to pH ˜6 using 4M hydrochloric acid and extracted with dichloromethane (×4). The combined organic fractions were dried with sodium sulfate, filtered and the solvent was removed from the filtrate under reduced pressure. Purification by silica gel chromatography (methanol/dichloromethane: 2-5%) gave the title compound as a mixture of enantiomers.

Workup

  1. additionAfter this time the reaction was poured onto water
  2. extractionextracted with ethyl acetate (×2)
  3. dry with materialThe combined organic fractions were dried with sodium sulfate
  4. customthe solvent was removed from the filtrate under reduced pressure
  5. customto provide 1.36
  6. additionas a mixture of enantiomers which
  7. customwas used without further purification
  8. customwas placed in 6 mL tetrahydrofuran at ambient temperature
  9. addition23.9 mL of 1M sodium hydroxide and 23.8 mg tetrabutylammonium hydrogensulfate were added
  10. temperatureThe reaction was heated to 80° C. where it
  11. temperaturewas maintained for 22 h
  12. customAfter this time, reaction mixture
  13. temperaturewas cooled to ambient temperature
  14. washwashed with diethyl ether (×2)
  15. extractionextracted with dichloromethane (×4)
  16. dry with materialThe combined organic fractions were dried with sodium sulfate
  17. filtrationfiltered
  18. customthe solvent was removed from the filtrate under reduced pressure
  19. customPurification by silica gel chromatography (methanol/dichloromethane: 2-5%)

Sources & evidence

ORD record
ord-3673d5ef8d284023ad3aef693bdb4bea
Source dataset
uspto-grants-2015_11
Patent number
US09187478B2

Reaction notes

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