2,4-Dichlorobenzylamine → N-(2,4-Dichlorobenzyl)-7-[(3RS,5RS)-3,5-dimethylpiperazin-1-yl]-6-fluoro-8-methoxy-1-(2,2,2-trifluoroethyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide

HRID 2099315Notes

Reaction equation

HRID 2099315 reaction equation
C(N(CC)C(C)C)(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH3:43][C@H:44]1[NH:49][C@@H:48]([CH3:50])[CH2:47][N:46]([C:51]2[C:60]([O:61][CH3:62])=[C:59]3[C:54]([C:55](=[O:71])[C:56]([C:68](O)=[O:69])=[CH:57][N:58]3[CH2:63][C:64]([F:67])([F:66])[F:65])=[CH:53][C:52]=2[F:72])[CH2:45]1.[Cl:73][C:74]1[CH:81]=[C:80]([Cl:82])[CH:79]=[CH:78][C:75]=1[CH2:76][NH2:77].C(#N)C>CN(C)C=O.C(OCC)(=O)C>[Cl:73][C:74]1[CH:81]=[C:80]([Cl:82])[CH:79]=[CH:78][C:75]=1[CH2:76][NH:77][C:68]([C:56]1[C:55](=[O:71])[C:54]2[C:59](=[C:60]([O:61][CH3:62])[C:51]([N:46]3[CH2:45][CH:44]([CH3:43])[NH:49][CH:48]([CH3:50])[CH2:47]3)=[C:52]([F:72])[CH:53]=2)[N:58]([CH2:63][C:64]([F:66])([F:67])[F:65])[CH:57]=1)=[O:69]

Participants

8

Reactant 5

HCID 14852,4-DichlorobenzylamineHCID 6342AcetonitrileHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 577941837-(cis-3,5-Dimethylpiperazin-1-yl)-6-fluoro-8-methoxy-1-(2,2,2-trifluoroethyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Product 1

HCID 76607220N-(2,4-Dichlorobenzyl)-7-[(3RS,5RS)-3,5-dimethylpiperazin-1-yl]-6-fluoro-8-methoxy-1-(2,2,2-trifluoroethyl)-4-oxo-1,4-dihydroquinoline-3-carboxamideYield 0.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under argon, 7.52 g (58.2 mmol) of N,N-diisopropylethylamine and 7.71 g (14.81 mmol) of PyBOP are added to 5.20 g (10.58 mmol) of 7-(cis-3,5-dimethylpiperazin-1-yl)-6-fluoro-8-methoxy-1-(2,2,2-trifluoroethyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydroformate (Example 31A) and 3.73 g (21.2 mmol) of 2,4-dichlorobenzylamine in 10.7 ml of dimethylformamide and the mixture is stirred at room temperature overnight. The reaction mixture is diluted with 1500 ml of ethyl acetate and washed three times with water. The combined aqueous phases are extracted once with ethyl acetate. The combined organic phases are washed with a saturated sodium chloride solution, dried over sodium sulfate and concentrated. The residue is stirred with 30 ml of acetonitrile. The solid is then collected by filtration and dried under high vacuum. 6.80 mg of the target compound are obtained as a cocrystallisate with 1 eq. of acetonitrile. For smaller quantities the residue after extraction can be purified by preparative HPLC (by one of the methods 5 to 8).

Workup

  1. washwashed three times with water
  2. extractionThe combined aqueous phases are extracted once with ethyl acetate
  3. washThe combined organic phases are washed with a saturated sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. stirringThe residue is stirred with 30 ml of acetonitrile
  7. filtrationThe solid is then collected by filtration
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-405ae29eece54f16b64592e028ce1f0f
Source dataset
uspto-grants-2009_08
Patent number
US07569563B2

Reaction notes

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