HCID 12231775, compound → HCID 59427353, compound

HRID 1013695Notes

Reaction equation

HRID 1013695 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:10]=[CH:11][N:12]=[C:13]3[C:18]=2[N:17]=[CH:16][C:15]([O:19][CH3:20])=[CH:14]3)=[CH:4][CH:3]=1.[C:21]1([C:27]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:30]([NH2:37])=[N:29][N:28]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:20][O:19][C:15]1[CH:14]=[C:13]2[C:18]([C:9]([O:8][C:5]3[CH:4]=[CH:3][C:2]([NH:37][C:30]4[C:31]5[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=5)[C:27]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)=[N:28][N:29]=4)=[N:7][CH:6]=3)=[CH:10][CH:11]=[N:12]2)=[N:17][CH:16]=1

Participants

5

Reactant 3

HCID 12231775HCID 12231775, compoundHCID 23676156Sodium t-butoxideHCID 86628669HCID 86628669, compound

Product 1

HCID 59427353HCID 59427353, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

In a nitrogen purged sealed tube was added toluene (1.5 mL), purged the solvent with nitrogen for 5 minutes and sealed the tube. To the tube was added 8-(6-bromopyridin-3-yloxy)-3-methoxy-1,5-naphthyridine (0.100 g, 0.301 mmol), 4-phenylphthalazin-1-amine (0.080 g, 0.361 mmol), sodium tert-butoxide (0.072 g, 0.753 mmol), and the tube was again purged with nitrogen and sealed. Added tBu X-phos (0.013 g, 0.030 mmol), tris(dibenzylideneacetone)dipalladium (o) (0.007 g, 0.008 mmol), purged the reaction with nitrogen, sealed, heated the tube to 100° C., stirring for 24 h. The reaction was cooled to RT, filtered through pad of silica gel, washed with 100% CH2Cl2:MeOH(90:110)/CH2Cl2 and concentrated. The crude was purified using reverse phase chromatography, extracted the concentrated product fractions into DCM, washed the organic layer 1× with sodium carbonate, 1×H2O, dried with Na2SO4, filtered solution through fritted funnel, and concentrated the filtrate to afford N-(5-(7-methoxy-1,5-naphthyridin-4-yloxy)pyridin-2-yl)-4-phenylphthalazin-1-amine as light yellow solid. MS [M+H]=473; Calc'd 472.5 for C28H20N6O2.

Workup

  1. customIn a nitrogen purged
  2. customsealed tube
  3. additionwas added toluene (1.5 mL)
  4. custompurged the solvent with nitrogen for 5 minutes
  5. customsealed the tube
  6. customthe tube was again purged with nitrogen
  7. customsealed
  8. customthe reaction with nitrogen
  9. customsealed
  10. temperatureThe reaction was cooled to RT
  11. filtrationfiltered through pad of silica gel
  12. washwashed with 100% CH2Cl2:MeOH(90:110)/CH2Cl2
  13. concentrationconcentrated
  14. customThe crude was purified
  15. extractionextracted the concentrated product fractions into DCM
  16. washwashed the organic layer 1× with sodium carbonate, 1×H2O
  17. dry with materialdried with Na2SO4
  18. filtrationfiltered solution through fritted funnel
  19. concentrationconcentrated the filtrate

Sources & evidence

ORD record
ord-7bd256f21f72455885cbd4859ea9ecf7
Source dataset
uspto-grants-2011_07
Patent number
US07981891B2

Reaction notes

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