2-Pyridinemethanamine → 7-(3,5-dimethyl-4-isoxazolyl)-6-(methoxy)-N4-(2-pyridinylmethyl)-3,4-quinolinediamine

HRID 1042998Notes

Reaction equation

HRID 1042998 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:14]3[C:15]([CH3:20])=[N:16][O:17][C:18]=3[CH3:19])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[N+:21]([O-])=O.[N:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH2:30][NH2:31]>C(#N)C>[CH3:20][C:15]1[C:14]([C:8]2[CH:7]=[C:6]3[C:11]([C:2]([NH:31][CH2:30][C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][N:24]=4)=[C:3]([NH2:21])[CH:4]=[N:5]3)=[CH:10][C:9]=2[O:12][CH3:13])=[C:18]([CH3:19])[O:17][N:16]=1

Participants

4

Reactant 2

HCID 195092-PyridinemethanamineHCID 574655804-(4-Chloro-6-methoxy-3-nitroquinolin-7-yl)-3,5-dimethylisoxazole

Product 1

HCID 672071317-(3,5-dimethyl-4-isoxazolyl)-6-(methoxy)-N4-(2-pyridinylmethyl)-3,4-quinolinediamine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

A solution of 4-chloro-7-(3,5-dimethyl-4-isoxazolyl)-6-(methoxy)-3-nitroquinoline (for a preparation see intermediate 18, 2.5 g,) and (2-pyridinylmethyl)amine (1.41 g) in acetonitrile (30 ml) were heated at 80° C. for 2 h. The mixture was extracted with DCM and the organic washed with a saturated solution of sodium hydrogen carbonate, dried over Na2SO4, filtered and concentrated to dryness. The residue was taken-up in diethyl ether, filtered and dried under vacuum. The residue was dissolved in ethanol (20 ml) and HCl (3.8 ml, conc.). Tin (II) chloride dihydrate (5.6 g) was then added in four portions and the reaction mixture was stirred for 1 h at 40° C. The mixture was hydrolysed using sodium hydroxide (1N), extracted with DCM and the organic were dried over Na2SO4. The mixture was filtered through Celite and concentrated to dryness. The crude product was purified by chromatography on silica gel eluting with DCM/methanol (56.5/3.5) to give 7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-N4-(pyridin-2-ylmethyl)quinoline-3,4-diamine (500 mg) as a clear brown foam.

Workup

  1. extractionThe mixture was extracted with DCM
  2. washthe organic washed with a saturated solution of sodium hydrogen carbonate
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. filtrationfiltered
  7. customdried under vacuum
  8. dissolutionThe residue was dissolved in ethanol (20 ml)
  9. additionTin (II) chloride dihydrate (5.6 g) was then added in four portions
  10. extractionextracted with DCM
  11. dry with materialthe organic were dried over Na2SO4
  12. filtrationThe mixture was filtered through Celite
  13. concentrationconcentrated to dryness
  14. customThe crude product was purified by chromatography on silica gel eluting with DCM/methanol (56.5/3.5)

Sources & evidence

ORD record
ord-fae28f6bbe244308bf169f3f939e9f66
Source dataset
uspto-grants-2013_10
Patent number
US08557984B2

Reaction notes

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