rel-(2R,6S)-2,6-dimethylpiperazine → 8-Cyano-1-cyclopropyl-7-[(3RS,5SR)-3,5-dimethylpiperazin-1-yl]-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid-hydrochloride

HRID 251851Notes

Reaction equation

HRID 251851 reaction equation
[Cl:1][C:2]1[C:11]([C:12]#[N:13])=[C:10]2[C:5]([C:6](=[O:20])[C:7]([C:17]([OH:19])=[O:18])=[CH:8][N:9]2[CH:14]2[CH2:16][CH2:15]2)=[CH:4][C:3]=1[F:21].[CH3:22][C@H:23]1[CH2:28][NH:27][CH2:26][C@@H:25]([CH3:29])[NH:24]1>C(#N)C>[ClH:1].[C:12]([C:11]1[C:2]([N:27]2[CH2:26][CH:25]([CH3:29])[NH:24][CH:23]([CH3:22])[CH2:28]2)=[C:3]([F:21])[CH:4]=[C:5]2[C:10]=1[N:9]([CH:14]1[CH2:16][CH2:15]1)[CH:8]=[C:7]([C:17]([OH:19])=[O:18])[C:6]2=[O:20])#[N:13]

Participants

4

Reactant 2

HCID 6950261rel-(2R,6S)-2,6-dimethylpiperazineHCID 153471917-Chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid

Product 1

HCID 668612758-Cyano-1-cyclopropyl-7-[(3RS,5SR)-3,5-dimethylpiperazin-1-yl]-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid-hydrochlorideYield 22.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 500.0 mg (1.63 mmol) of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (for preparation see: DE 19854357) and 446.8 mg (3.91 mmol) of cis-2,6-dimethylpiperazine in 50 ml of acetonitrile is stirred over night at 50° C. The solvent is removed completely on a rotary evaporator, the residue is taken up in 50 ml of water and the pH is adjusted to pH 11 with a 1N sodium hydroxide solution (the residue dissolves). The solution is then adjusted to pH 7 with 1N hydrochloric acid. The precipitate is filtered off, washed with water and diethylether and dried under high vacuum. 157 mg of the title compound are obtained. The filtrate is extracted with dichloromethane, the organic phase is concentrated and the residue is purified by RP-HPLC. An additional 351 mg of the title compound are obtained.

Workup

  1. customThe solvent is removed completely on a rotary evaporator
  2. dissolutiondissolves)
  3. filtrationThe precipitate is filtered off
  4. washwashed with water and diethylether
  5. customdried under high vacuum

Sources & evidence

ORD record
ord-227bc7ad1c304261aff4596961b63a36
Source dataset
uspto-grants-2011_01
Patent number
US07867992B2

Reaction notes

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