Triethylamine → 7-(2-Aminomethyl-1,4-dioxa-7-azaspiro[4.4]non-7-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,8-naphthyridine-3-carboxylic acid dihydrochloride

HRID 846701Notes

Reaction equation

HRID 846701 reaction equation
C(OC([NH:8][CH2:9][CH:10]1[CH2:14][O:13][C:12]2([CH2:18][CH2:17][NH:16][CH2:15]2)[O:11]1)=O)(C)(C)C.C([O:21][C:22]([C:24]1[CH2:25][N:26]([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:37]=2[F:43])[C:27]2[C:32]([CH:33]=1)=[CH:31][C:30]([F:34])=[C:29]([Cl:35])[N:28]=2)=[O:23])C.C(N(CC)CC)C>N1C=CC=CC=1>[ClH:35].[ClH:35].[NH2:8][CH2:9][CH:10]1[CH2:14][O:13][C:12]2([CH2:18][CH2:17][N:16]([C:29]3[N:28]=[C:27]4[C:32]([CH:33]=[C:24]([C:22]([OH:23])=[O:21])[CH2:25][N:26]4[C:36]4[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:37]=4[F:43])=[CH:31][C:30]=3[F:34])[CH2:15]2)[O:11]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 198832752-t-Butoxycarbonylaminomethyl-1,4-dioxa-7-azaspiro[4.4]nonaneHCID 867460661-(2,4-Difluorophenyl)-7-chloro-6-fluoro-1,8-naphthyridine-3-carboxylic acid ethyl ester

Product 1

HCID 678359397-(2-Aminomethyl-1,4-dioxa-7-azaspiro[4.4]non-7-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,8-naphthyridine-3-carboxylic acid dihydrochlorideYield 232.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
45 °C

Procedure

In a reaction similar to that of Step 1 Example 387, into oven-dried glassware maintained under dry N2 were placed 0.733 g (2.8 mmol) of 2-t-butoxycarbonylaminomethyl-1,4-dioxa-7-azaspiro[4.4]nonane, from Step 5 Example 159, 0.725 g (1.9 mmol) of 1-(2,4-difluorophenyl)-7-chloro-6-fluoro-1,8-naphthyridine-3-carboxylic acid ethyl ester dissolved in 20 mL of pyridine and 1.06 mL (7.6 mmol) of triethylamine. The reaction was stirred at 45° C. for 6 hours, then the solvent was removed in a rotary evaporator after toluene was added to azeotrope the pyridine. The residue was dissolved in 60 mL of methylene chloride, washed with 2×50 mL of water and dried over anhydrous sodium sulfate and filtered. The solvent was removed by evaporation and the product was washed with hexane and dried to afford 1.184 g of the title compound, MS (DCl) M/Z 605 (M+H). NMR (CDCl3) d 1.40 (t, 3H, J=6 Hz), 1.47 (s, 9H), 2.03 (m, 2H), 3.16 (m, 2H), 3.51 (m, 4H), 3.69 (m, 1H), 4.04 (m, 1H), 4.22 (m, 1H), 4.38 (q, 2H, J=6 Hz), 4.81 (m, 1H), 7.05 (m, 2H), 7.38 (m, 1H), 8.09 (dd, 1H, J=12, 1.5 Hz), 8.39 (d, 1H, J=1.5 Hz).

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 in a rotary evaporator after toluene
  5. additionwas added
  6. dissolutionThe residue was dissolved in 60 mL of methylene chloride
  7. washwashed with 2×50 mL of water
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customThe solvent was removed by evaporation
  11. washthe product was washed with hexane
  12. customdried

Sources & evidence

ORD record
ord-4faf6975aee54864a5f472150729c2a7
Source dataset
uspto-grants-1992_08
Patent number
US05137892

Reaction notes

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