1,5-Dioxa-9-azaspiro(5.5)undecane → 7-(1,5-Dioxa-9-azaspiro[5.5]undec-9-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,8-naphthyridine-3-carboxylic acid

HRID 846703Notes

Reaction equation

HRID 846703 reaction equation
[O:1]1[C:6]2([CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)[O:5][CH2:4][CH2:3][CH2:2]1.C([O:14][C:15]([C:17]1[CH2:18][N:19]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=2[F:36])[C:20]2[C:25]([CH:26]=1)=[CH:24][C:23]([F:27])=[C:22](Cl)[N:21]=2)=[O:16])C>N1C=CC=CC=1>[O:1]1[C:6]2([CH2:11][CH2:10][N:9]([C:22]3[N:21]=[C:20]4[C:25]([CH:26]=[C:17]([C:15]([OH:16])=[O:14])[CH2:18][N:19]4[C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=4[F:36])=[CH:24][C:23]=3[F:27])[CH2:8][CH2:7]2)[O:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 27372161,5-Dioxa-9-azaspiro(5.5)undecaneHCID 867460661-(2,4-Difluorophenyl)-7-chloro-6-fluoro-1,8-naphthyridine-3-carboxylic acid ethyl ester

Product 1

HCID 198832927-(1,5-Dioxa-9-azaspiro[5.5]undec-9-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,8-naphthyridine-3-carboxylic acidYield 96%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

In a reaction similar to that of Step 1, Example 387, into oven-dried glassware maintained under dry N2 were placed 0.622 g (3.96 mmol) of 1,5-dioxa-9-azaspiro[5.5]undecane, from Step 4 Example 196, 0.500 g (1.3 mmol) of 7-chloro-6-fluoro-1-(2,4-difluorophenyl)-1,8-naphthyridine-3-carboxylic acid ethyl ester, and 15 mL of dry pyridine. The reaction was stirred at room temperature for 5 hours, then the solvent was removed by evaporation. The residue was dissolved in 50 mL of methylene chloride, which was washed with 50 mL of 5% sodium bicarbonate and 50 mL of water, dried over anhydrous sodium sulfate, filtered and dried. The product was purified by recrystallization from ethanol/water, isolated by filtration and dried under vacuum to afford 0.576 g of the title compound, mp 177°-178° C., MS (DCl/NH3) M/Z 504 (M+H) (base). Analysis calculated for C25H24F3N3O5 : C, 59.64; H, 4.80; N, 8.35. Found: C, 61.13; H, 5.09; N, 8.36.

Workup

  1. customIn a reaction similar to that of Step 1, Example 387
  2. custominto oven-dried glassware
  3. temperaturemaintained under dry N2
  4. customthe solvent was removed by evaporation
  5. dissolutionThe residue was dissolved in 50 mL of methylene chloride
  6. washwhich was washed with 50 mL of 5% sodium bicarbonate and 50 mL of water
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customdried
  10. customThe product was purified by recrystallization from ethanol/water
  11. customisolated by filtration
  12. customdried under vacuum

Sources & evidence

ORD record
ord-a7dcf0d657114c46b661d353c7ce0ac1
Source dataset
uspto-grants-1992_08
Patent number
US05137892

Reaction notes

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