Acetonitrile → n-[6-Chloro-2-[methyl[3-(methylamino)propyl]amino]-5-quinolinyl]-1-cyclohexyl-cyclopropanecarboxamide, hydrochloride

HRID 2217821Notes

Reaction equation

HRID 2217821 reaction equation
[CH:1]1([C:7]2([C:10]([NH:12][C:13]3[C:22]([Cl:23])=[CH:21][CH:20]=[C:19]4[C:14]=3[CH:15]=[CH:16][C:17](Cl)=[N:18]4)=[O:11])[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C[N:26]([CH3:31])[CH2:27][CH2:28][CH2:29][NH2:30].[C:32](#N)C>>[ClH:23].[Cl:23][C:22]1[C:13]([NH:12][C:10]([C:7]2([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)[CH2:9][CH2:8]2)=[O:11])=[C:14]2[C:19](=[CH:20][CH:21]=1)[N:18]=[C:17]([N:30]([CH3:32])[CH2:29][CH2:28][CH2:27][NH:26][CH3:31])[CH:16]=[CH:15]2

Participants

4

Reactant 3

HCID 6342AcetonitrileHCID 7993N,N-Dimethyl-1,3-propanediamineHCID 860130111-Cyclohexyl-N-(2,6-dichloro-5-quinolinyl)-cyclopropanecarboxamide

Product 1

HCID 11178787n-[6-Chloro-2-[methyl[3-(methylamino)propyl]amino]-5-quinolinyl]-1-cyclohexyl-cyclopropanecarboxamide, hydrochloride

Conditions

Temperature
100 °C

Procedure

To a 10 mL vial was added 1-cyclohexyl-N-(2,6-dichloro-5-quinolinyl)-cyclopropanecarboxamide (example 26 (b)) (0.13 g), N,N-dimethyl-1,3-propanediamine (0.13 mL) and acetonitrile (3 mL). The vial was sealed and heated at 100° C. in a microwave for 20 minutes followed by 30 minutes at 110° C. The solvent was removed from the cooled reaction under reduced pressure, saturated aqueous sodium hydrogen carbonate solution (30 mL) was added and the mixture was extracted with dichloromethane (3×50 mL). The combined organics were washed with water (50 mL) and brine (50 mL) before being dried, filtered and concentrated. Purification (Varian SCX cartridge, using methanol and 10% ammonia in methanol as eluant) gave a crude product which was further purified by chromatography (SiO2, ammonia:methanol:dichloromethane, 1:2.5:96.5 as eluant). The product was converted to its hydrochloride salt by dissolution in dichloromethane and treatment with 4M hydrogen chloride in 1,4 dioxane (5 mL). Removal of volatiles and recrystallisation from methanol/acetonitrile afforded the title compound (0.075 g).

Workup

  1. customThe vial was sealed
  2. customThe solvent was removed from the cooled reaction under reduced pressure, saturated aqueous sodium hydrogen carbonate solution (30 mL)
  3. additionwas added
  4. extractionthe mixture was extracted with dichloromethane (3×50 mL)
  5. washThe combined organics were washed with water (50 mL) and brine (50 mL)
  6. custombefore being dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification (Varian SCX cartridge, using methanol and 10% ammonia in methanol as eluant)
  10. customgave a crude product which
  11. customwas further purified by chromatography (SiO2, ammonia:methanol:dichloromethane, 1:2.5:96.5 as eluant)
  12. dissolutionThe product was converted to its hydrochloride salt by dissolution in dichloromethane
  13. customRemoval of volatiles and recrystallisation from methanol/acetonitrile

Sources & evidence

ORD record
ord-5fb6d0f1eb8d476ebc815f680d6c527f
Source dataset
uspto-grants-2008_08
Patent number
US07408065B2

Reaction notes

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