Dichloromethane → HCID 66924231, compound

HRID 1362834Notes

Reaction equation

HRID 1362834 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:17])=[C:11](F)[C:12]=3[O:14][CH3:15])[C:7](=[O:18])[C:6]([C:19]([OH:21])=[O:20])=[CH:5]2)[CH2:3][CH2:2]1.[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH:32]([NH:35][CH:36]2[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].ClCCl>C(#N)C>[C:22]([O:26][C:27]([N:29]1[CH2:30][CH2:31][CH:32]([NH:35][CH:36]2[CH2:41][CH2:40][N:39]([C:11]3[C:12]([O:14][CH3:15])=[C:13]4[C:8]([C:7](=[O:18])[C:6]([C:19]([OH:21])=[O:20])=[CH:5][N:4]4[CH:1]4[CH2:3][CH2:2]4)=[CH:9][C:10]=3[F:17])[CH2:38][CH2:37]2)[CH2:33][CH2:34]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 70194651-Cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acidHCID 59898565HCID 59898565, compound

Product 1

HCID 66924231HCID 66924231, compoundYield 17.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
62.5 °C

Procedure

To a stirred solution of 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (295 mg, 1.0 mmol) in acetonitrile (5 mL) was added 4-(piperidin-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (339 mg, 1.2 mmol) followed by the addition of 8-diazabicyclo[5.4.0]undec-7-ene (DBU, 182 mg, 1.2 mmol). The resulting stirred solution was then heated in a 60-65° C. oil bath for two days. The cooled reaction mixture was filtered through a fritted funnel. The filtrate was condensed to dryness. Dichloromethane was added into this residue and washed with water twice. The resulting organic layer was washed one more time with saturated brine and dried over sodium sulfate. The solvent was removed under reduced pressure to give crude material as light brown syrup. This crude product was further purified with 10% methanol in dichloromethane by preparative TLC plate to afford pure title product as yellow solid (100 mg). ESI MS m/z 559 (M+H+); 1H NMR (400 MHz, CDCl3) δ 8.73 (s, 1H), 7.76 (d, J=12.4 Hz, 1H), 3.98 (m, 3H), 3.71 (s, 3H), 3.51 (d, J=12.1 Hz, 2H), 3.17 (t, J=12.3 Hz, 2H), 2.76 (br s, 1H), 1.92 (d, J=11.8 Hz, 2H), 1.83 (d, J=11.6 Hz, 2H), 1.49 (q, J=8.6 Hz, 2H), 1.38 (s, 9H), 1.20 (q, J=7.9 Hz, 2H), 1.15 (d, J=7.1 Hz, 2H), 0.94 (d, J=5.6 Hz, 2H).

Workup

  1. customThe cooled reaction mixture
  2. filtrationwas filtered through a fritted funnel
  3. customcondensed to dryness
  4. washwashed with water twice
  5. washThe resulting organic layer was washed one more time with saturated brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customto give crude material as light brown syrup
  9. customThis crude product was further purified with 10% methanol in dichloromethane by preparative TLC plate

Sources & evidence

ORD record
ord-e403ab9b256b4159a69ff81520c986d7
Source dataset
uspto-grants-2011_02
Patent number
US07884099B2

Reaction notes

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