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

HRID 443208Notes

Reaction equation

HRID 443208 reaction equation
[CH2:1]([O:3][C:4](=[O:24])[C:5]([C:12](=[O:23])[C:13]1[CH:18]=[C:17]([F:19])[C:16](F)=[C:15]([F:21])[C:14]=1F)=[CH:6][NH:7][N:8]([CH:10]=[O:11])[CH3:9])[CH3:2].[CH3:25][N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:5]1[C:12](=[O:23])[C:13]2[C:14](=[C:15]([F:21])[C:16]([N:29]3[CH2:30][CH2:31][N:26]([CH3:25])[CH2:27][CH2:28]3)=[C:17]([F:19])[CH:18]=2)[N:7]([N:8]([CH3:9])[CH:10]=[O:11])[CH:6]=1)=[O:24])[CH3:2]

Participants

4

Reactant 2

HCID 531671-Methylpiperazine2×HCID 178472136HCID 178472136, compound

Product 1

HCID 544708606,8-Difluoro-1-(formylmethylamino)-7-(4-methylpiperazin-1-YL)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl esterYield 88.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A suspension of 4.92 g (15 mmol) of 3-(2-formyl-2-methylhydrazino)-2-(2,3,4,5-tetrafluorobenzoyl)acrylic acid ethyl ester and 3.41 ml (30.1 mmol) of N-methyl-piperazine in 15 ml of toluene were heated at reflux for 7.5 hours after which a clear, yellow solution was formed. After the addition of further 2.08 ml of N-methyl-piperazine the mixture was heated for 2 hours, cooled and evaporated at 49° C./130 torr. The yellowish oil (13.7 g) was taken up in 30 ml of dichloromethane, washed with 50 ml of water and subsequently twice with each 7.5 ml of half-saturated brine. The aqueous extracts were washed twice with each 15 ml of dichlormethane, the organic phases united, dried over magnesium sulphate, filtered and evaporated at 47° C./20 torr. The crystalline, beige residue (6.1 g) was suspended in 40 ml of tert.-butylmethyl ether, vigorously digested for 50 min., the crystals filtered, washed twice with each 10 ml of tert.-butylmethyl ether and dried at 45° C./13 torr. 5.41 g (88%) of 6,8-difluoro-1,4-dihydro-1-(N-methylformamido)7-(4-methyl- 1-piperazinyl)-4-oxo-3-quinoline-carboxylic acid ethyl ester were obtained as beige crystals of mp 180° C.

Workup

  1. temperaturewere heated
  2. temperatureat reflux for 7.5 hours after which a clear, yellow solution
  3. customwas formed
  4. temperaturewas heated for 2 hours
  5. temperaturecooled
  6. customevaporated at 49° C./130 torr
  7. washwashed with 50 ml of water and subsequently twice with each 7.5 ml of half-saturated brine
  8. washThe aqueous extracts were washed twice with each 15 ml of dichlormethane
  9. dry with materialdried over magnesium sulphate
  10. filtrationfiltered
  11. customevaporated at 47° C./20 torr
  12. filtrationthe crystals filtered
  13. washwashed twice with each 10 ml of tert.-butylmethyl ether
  14. customdried at 45° C./13 torr

Sources & evidence

ORD record
ord-dd278d90f3f44241a5f10f903e0ee951
Source dataset
uspto-grants-1999_04
Patent number
US05892040

Reaction notes

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