Dimethyl Sulfoxide → 1-(3-Amino-4,6-difluorophenyl)-7-(7-amino-5-azaspiro[2.4]-heptan-5-yl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride

HRID 1415959Notes

Reaction equation

HRID 1415959 reaction equation
CS(C)=O.C(OC([NH:12][CH:13]1[C:17]2([CH2:19][CH2:18]2)[CH2:16][NH:15][CH2:14]1)=O)(C)(C)C.C(N(CC)CC)C.[NH2:27][C:28]1[CH:29]=[C:30]([N:36]2[C:45]3[C:40](=[CH:41][C:42]([F:47])=[C:43]([Cl:46])[N:44]=3)[C:39](=[O:48])[C:38]([C:49]([OH:51])=[O:50])=[CH:37]2)[C:31]([F:35])=[CH:32][C:33]=1[F:34]>C(OCC)C>[ClH:46].[NH2:27][C:28]1[CH:29]=[C:30]([N:36]2[C:45]3[C:40](=[CH:41][C:42]([F:47])=[C:43]([N:15]4[CH2:14][CH:13]([NH2:12])[C:17]5([CH2:18][CH2:19]5)[CH2:16]4)[N:44]=3)[C:39](=[O:48])[C:38]([C:49]([OH:51])=[O:50])=[CH:37]2)[C:31]([F:35])=[CH:32][C:33]=1[F:34]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 110899701-(3-Amino-4,6-difluorophenyl)-7-chloro-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acidHCID 14930995Tert-butyl 5-azaspiro[2.4]heptan-7-ylcarbamate

Product 1

HCID 699601751-(3-Amino-4,6-difluorophenyl)-7-(7-amino-5-azaspiro[2.4]-heptan-5-yl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochlorideYield 46%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

To 2 ml of dimethylsulfoxide were added 173 mg of 7-tert-butyloxycarbonylamino-5-azaspiro[2.4]heptane B form and 164 mg of triethylamine. With heating and stirring at 80° C., 200 mg of 1-(3-amino-4,6-difluorophenyl)-7-chloro-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid was added to the solution, which was stirred at the temperature overnight. After the reaction solution was allowed to cool down, diethyl ether was added thereto. The diethyl ether layer was concentrated in vacua. The residue was combined with chloroform, washed with water, and dried over magnesium sulfate. The solvent was distilled off. Diethyl ether was added to the residue whereupon the solid was collected by filtration. To the solid were added 30 ml of chloroform and 5 ml of 4N hydrochloric acid/dioxane. After stirring at room temperature for 2 hours, the reaction solution was concentrated in vacua. Diethyl ether was added to the residue whereupon the solid was collected by filtration and washed with diethyl ether to give 120 mg of the title compound.

Workup

  1. temperatureWith heating
  2. stirringwas stirred at the temperature overnight
  3. temperatureto cool down
  4. concentrationThe diethyl ether layer was concentrated in vacua
  5. washwashed with water
  6. dry with materialdried over magnesium sulfate
  7. distillationThe solvent was distilled off
  8. additionDiethyl ether was added to the residue whereupon the solid
  9. filtrationwas collected by filtration
  10. additionTo the solid were added 30 ml of chloroform and 5 ml of 4N hydrochloric acid/dioxane
  11. stirringAfter stirring at room temperature for 2 hours
  12. concentrationthe reaction solution was concentrated in vacua
  13. additionDiethyl ether was added to the residue whereupon the solid
  14. filtrationwas collected by filtration
  15. washwashed with diethyl ether

Sources & evidence

ORD record
ord-d811ef60cd9044418ea07ac909436f24
Source dataset
uspto-grants-1999_06
Patent number
US05910498

Reaction notes

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