1-Methyl-2-(tributylstannyl)-1H-imidazole → N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)-4-(1-methyl-1H-imidazol-2-yl)phthalazin-1-amine

HRID 503540Notes

Reaction equation

HRID 503540 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[Sn](CCCC)(CCCC)CCCC.Cl[C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][C:39]3[C:48]4[C:43](=[CH:44][C:45]([O:49][CH3:50])=[CH:46][N:47]=4)[N:42]=[CH:41][CH:40]=3)=[CH:34][CH:33]=2)=[N:23][N:22]=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:50][O:49][C:45]1[CH:44]=[C:43]2[C:48]([C:39]([O:38][C:35]3[CH:36]=[CH:37][C:32]([NH:31][C:24]4[C:25]5[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=5)[C:21]([C:3]5[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=5)=[N:22][N:23]=4)=[CH:33][CH:34]=3)=[CH:40][CH:41]=[N:42]2)=[N:47][CH:46]=1

Participants

4

Reactant 2

HCID 27632521-Methyl-2-(tributylstannyl)-1H-imidazoleHCID 866286654-chloro-N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)phthalazin-1-amine

Product 1

HCID 67318303N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)-4-(1-methyl-1H-imidazol-2-yl)phthalazin-1-amineYield 29.4%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
100 °C

Procedure

In a nitrogen purged sealed tube was added 1,4-dioxane (1.35 mL), and the solution was purged with nitrogen for 5 minutes, then sealed. 1-Methyl-2-(tributylstannyl)-1H-imidazole (0.311 g, 0.837 mmol), 4-chloro-N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)phthalazin-1-amine (0.120 g, 0.279 mmol) were added to the tube, which was then purged with nitrogen and sealed. To the tube was added 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (0.102 mg, 0.140 mmol), and the tube was purged with nitrogen, sealed, and heated to 100° C., while stirring the reaction for 17 hours. The reaction was cooled to RT, and concentrated. The concentrate was purified using reverse phase chromatography, the product fractions were concentrated, extracted into DCM, washed once with sodium carbonate and once with water, upon which the title compound precipiated. The solids were filtered, washed with water, air dried to yield N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)-4-(1-methyl-1H-imidazol-2-yl)phthalazin-1-amine (0.039 g) as light yellow solid. MS [M+H]=476.0; Calc'd 475.5 for C27H21N7O2.

Workup

  1. customIn a nitrogen purged
  2. customsealed tube
  3. additionwas added 1,4-dioxane (1.35 mL)
  4. customthe solution was purged with nitrogen for 5 minutes
  5. customsealed
  6. customwas then purged with nitrogen
  7. customsealed
  8. customthe tube was purged with nitrogen
  9. customsealed
  10. customthe reaction for 17 hours
  11. temperatureThe reaction was cooled to RT
  12. concentrationconcentrated
  13. customThe concentrate was purified
  14. concentrationthe product fractions were concentrated
  15. extractionextracted into DCM
  16. washwashed once with sodium carbonate and once with water, upon which the title compound precipiated
  17. filtrationThe solids were filtered
  18. washwashed with water, air
  19. customdried

Sources & evidence

ORD record
ord-d167b8bd2ff5440c90e97664a6b3d613
Source dataset
uspto-grants-2010_08
Patent number
US07776857B2

Reaction notes

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