Sodium Carbonate → 6,8-Difluoro-1-(formylmethylamino)-7-(4-methylpiperazin-1-YL)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester

HRID 443210

반응식

HRID 443210 반응식
C(OC(=O)CC=NNCC=O)C.[CH3:13][CH2:14][O-:15].CC[O-].[Mg+2].FC1C(F)=C(F)C(F)=CC=1C(Cl)=O.C(=O)([O-])[O-].[Na+].[Na+].[CH3:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1.C(O[C:49](=[O:69])[C:50]([C:57](=[O:68])[C:58]1[CH:63]=[C:62]([F:64])[C:61](F)=[C:60]([F:66])[C:59]=1F)=[CH:51][NH:52][N:53]([CH:55]=[O:56])[CH3:54])C>C(OCC)(=O)C.O.C(O)=O>[CH2:14]([O:15][C:49]([C:50]1[C:57](=[O:68])[C:58]2[C:59](=[C:60]([F:66])[C:61]([N:43]3[CH2:44][CH2:45][N:40]([CH3:39])[CH2:41][CH2:42]3)=[C:62]([F:64])[CH:63]=2)[N:52]([N:53]([CH3:54])[CH:55]=[O:56])[CH:51]=1)=[O:69])[CH3:13]

참가 물질

10

반응물 6

HCID 10340Sodium CarbonateHCID 531671-MethylpiperazineHCID 164963Magnesium ethanolateHCID 27336892,3,4,5-Tetrafluorobenzoyl chlorideHCID 867540523-(Formylmethylhydrazono)-propionic acid ethyl esterHCID 178472136HCID 178472136, 화합물

생성물 1

HCID 544708606,8-Difluoro-1-(formylmethylamino)-7-(4-methylpiperazin-1-YL)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester

시약·촉매·용매 3

HCID 284Formic Acid용매HCID 962Water용매HCID 8857Ethyl Acetate용매2회

실험 절차

A yellow suspension of 8.61 g (50 mmol) of 3-(formylmethylhydrazono)-propionic acid ethyl ester and 5.72 g (50 mmol) of magnesium ethylate in 30 ml of ethyl acetate were heated at reflux for 65 min. The solution was cooled to 0°-5° C., and at this temperature a solution of 10.63 g (50 mmol) of 2,3,4,5-tetra-fluoro-benzoic acid chloride in 10 ml of ethyl acetate was added dropwise in the course of 20 min. Subsequently the suspension was stirred for 30 min. in the cold and afterwards for 18.5 hours at room temperature. After the addition of a solution of 7.0 ml of 85% formic acid in 50 ml of water the mixture was well mixed and the two phases separated. The aqueous phase was extracted twice with each 50 ml of ethyl acetate, the united organic phases dried over sodium sulphate, filtered and evaporated at 50° C./20 torr. The residue of 3-(2-formyl-2-methyl-hydrazino)-2-(2,3,4,5-tetrafluorobenzoyl)acrylic acid ethyl ester (18.81 g) was dissolved in 55 ml of butyl acetate, 5.83 g (55 nmol) of sodium carbonate were added, and the mixture was heated with stirring for 25 min. at reflux. 11.1 ml (100 mmol) of N-methylpiperazine were added to the resulting suspension of 3-(2-formyl-2-methyl-hydrazino)-2-(2,3,4,5-tetrafluorobenzoyl)acrylic acid ethyl ester and heated for 4.5 hours under reflux using a water trap, in the course of which the temperature rose from 114° to 125° C. The suspension was evaporated at 50° C./20 torr and the resulting brown residue (31.8 g) worked up in analogy to Example 3 resulting in 10.2 g (50%) of 6.8-difluoro-1,4-dihydro-1-(N-methylformamido)-7-(4-methyl- 1-piperazinyl)-4-oxo-3-quinoline-carboxylic acid ethyl ester as yellowish crystals of mp 178° C.

후처리

  1. temperaturewere heated
  2. temperatureat reflux for 65 min
  3. temperatureThe solution was cooled to 0°-5° C.
  4. additionwas well mixed
  5. customthe two phases separated
  6. extractionThe aqueous phase was extracted twice with each 50 ml of ethyl acetate
  7. dry with materialthe united organic phases dried over sodium sulphate
  8. filtrationfiltered
  9. customevaporated at 50° C./20 torr
  10. dissolutionThe residue of 3-(2-formyl-2-methyl-hydrazino)-2-(2,3,4,5-tetrafluorobenzoyl)acrylic acid ethyl ester (18.81 g) was dissolved in 55 ml of butyl acetate
  11. temperaturethe mixture was heated
  12. stirringwith stirring for 25 min.
  13. temperatureat reflux
  14. temperatureheated for 4.5 hours
  15. temperatureunder reflux
  16. customrose from 114° to 125° C
  17. customThe suspension was evaporated at 50° C./20 torr

출처 및 근거

ORD 기록
ord-d4923dd1702f4f9f8e49f0ac6c2209c0
출처 데이터셋
uspto-grants-1999_04
특허 번호
US05892040

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