Triphenylphosphine → 4-Chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

HRID 347324

Reaction equation

HRID 347324 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[Cl:15][C:16]1[C:25]2[C:20](=[CH:21][C:22]([OH:28])=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][C:17]=1[C:29]#[N:30].O[CH2:32][CH2:33][CH2:34][N:35]1[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl.O>[Cl:15][C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:28][CH2:32][CH2:33][CH2:34][N:35]3[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]3)=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][C:17]=1[C:29]#[N:30]

Participants

7

Reactant 4

HCID 11776Triphenylphosphine2×HCID 75555Diisopropyl diazene-1,2-dicarboxylate2×HCID 792083-(4-Methyl-1-piperazine)propan-1-olHCID 1357436694-Chloro-7-hydroxy-6-methoxyquinoline-3-carbonitrile

Product 1

HCID 117491774-Chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

A solution of diisopropyl azodicarboxylate (12.1 ml) in methylene chloride (50 ml) was added dropwise during 30 minutes to a stirred mixture of 4-chloro-3-cyano-7-hydroxy-6-methoxyquinoline (12 g), 1-(3-hydroxypropyl)-4-methylpiperazine (9.7 g), triphenylphosphine (16.1 g) and methylene chloride (200 ml) that had been cooled to 5° C. The resultant mixture was allowed to warm to ambient temperature and was then stirred for 1 hour. Further portions of diisopropyl azodicarboxylate (1.2 ml) and triphenylphosphine (1.6 g) were added and the mixture was stirred at ambient temperature for a further 1 hour. The mixture was poured into water and the organic layer was separated, washed with a saturated brine solution, dried over magnesium sulphate and evaporated. The material so obtained was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride and methanol as eluent. There was thus obtained the required starting material as a solid (14.5 g); NMR Spectrum: (DMSOd6) 1.95 (m, 2H), 2.13 (s, 3H), 2.24–2.5 (m, 10H), 4.0 (s, 3H), 4.25 (t, 2H), 7.43 (s, 1H), 7.51 (s, 1H), 8.95 (s, 1H); Mass Spectrum: M+H+ 375 and 377.

Workup

  1. temperatureto warm to ambient temperature
  2. stirringthe mixture was stirred at ambient temperature for a further 1 hour
  3. customthe organic layer was separated
  4. washwashed with a saturated brine solution
  5. dry with materialdried over magnesium sulphate
  6. customevaporated
  7. customThe material so obtained
  8. customwas purified by column chromatography on silica using
  9. temperatureincreasingly polar mixtures of methylene chloride and methanol as eluent
  10. customThere was thus obtained the

Sources & evidence

ORD record
ord-fccd35cb9d694bdd895561c7bbd803c6
Source dataset
uspto-grants-2007_02
Patent number
US07173136B2

Linked notes

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