Hydrochloric Acid → Ethyl 7-(3-acetylamino-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate

HRID 246964Notes

Reaction equation

HRID 246964 reaction equation
[C:1]([NH:4][CH:5]1[CH2:9][CH2:8][N:7]([C:10]2[C:27]([F:28])=[CH:26][C:13]([C:14]([C:16](=[CH:22]N(C)C)[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[O:15])=[C:12]([NH:29][C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=3[F:37])[N:11]=2)[CH2:6]1)(=[O:3])[CH3:2].Cl.C(Cl)(Cl)Cl.O>C(O)C.C(OCC)C>[C:1]([NH:4][CH:5]1[CH2:9][CH2:8][N:7]([C:10]2[N:11]=[C:12]3[C:13]([C:14](=[O:15])[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:22][N:29]3[C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=3[F:37])=[CH:26][C:27]=2[F:28])[CH2:6]1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 6212ChloroformHCID 70391376ethyl 2-[6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]-3-(N,N-dimethylamino)acrylate

Product 1

HCID 13652939Ethyl 7-(3-acetylamino-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylateYield 98.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

In 4 ml of ethanol was suspended 200 mg of ethyl 2-[6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]-3-(N,N-dimethylamino)acrylate, and 0.4 ml of 1N hydrochloric acid was added thereto, after which the resulting mixture was subjected to reaction at room temperature for 5 minutes. Subsequently, to the reaction mixture were added 10 ml of chloroform and 10 ml of water, and the organic layer was separated, washed successively with 10 ml of water and 10 ml of saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and to the crystalline material thus obtained was added 4 ml of diethyl ether, after which crystals were collected by filtration to obtain 180 mg (yield 98.6%) of ethyl 7-(3-acetylamino-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate. The physical properties of this compound were identical with those of the compound obtained in Example 39.

Workup

  1. additionwas added
  2. customafter which the resulting mixture was subjected to reaction at room temperature for 5 minutes
  3. customthe organic layer was separated
  4. washwashed successively with 10 ml of water and 10 ml of saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was removed by distillation under reduced pressure
  7. customto the crystalline material thus obtained
  8. filtrationafter which crystals were collected by filtration

Sources & evidence

ORD record
ord-e6aa2c6df7b54964a29031e59e1220f9
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

Loading…