Sodium Carbonate → 3-(4-(4-(7-Methoxy-1,5-naphthyridin-4-yloxy)phenylamino)phthalazin-1-yl)benzonitrile

HRID 1042804Notes

Reaction equation

HRID 1042804 reaction equation
[C:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1)#[N:2].Cl[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][C:31]3[C:40]4[C:35](=[CH:36][C:37]([O:41][CH3:42])=[CH:38][N:39]=4)[N:34]=[CH:33][CH:32]=3)=[CH:26][CH:25]=2)=[N:15][N:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>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]>[CH3:42][O:41][C:37]1[CH:36]=[C:35]2[C:40]([C:31]([O:30][C:27]3[CH:28]=[CH:29][C:24]([NH:23][C:16]4[C:17]5[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=5)[C:13]([C:7]5[CH:8]=[C:3]([CH:4]=[CH:5][CH:6]=5)[C:1]#[N:2])=[N:14][N:15]=4)=[CH:25][CH:26]=3)=[CH:32][CH:33]=[N:34]2)=[N:39][CH:38]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 866286654-chloro-N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)phthalazin-1-amine

Product 1

HCID 673179683-(4-(4-(7-Methoxy-1,5-naphthyridin-4-yloxy)phenylamino)phthalazin-1-yl)benzonitrile

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, 1,4-dioxane (1.4 mL) was added and the tube was purged with nitrogen for 5 min and sealed. 3-Cyanophenylboronic acid (0.056 g, 0.384 mmol), 4-chloro-N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)phthalazin-1-amine (0.150 g, 0.349 mmol), and 2.0 M sodium carbonate (0.349 mL, 0.698 mmol) were added to the tube, followed by 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (0.013 g, 0.017 mmol). The tube was purged with nitrogen, sealed, and the mixture was heated to 100° C. for 17 h. The mixture was allowed to cool to RT and was concentrated in vacuo. The crude material was purified by silica gel chromatography using 0-100% CH2Cl2:MeOH(90:10)/CH2Cl2. The remaining impurities were removed by diluting the crude with methanol causing a light yellow solid to precipitate, which were filtered and air dried to yield 3-(4-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenylamino)phthalazin-1-yl)benzonitrile. MS [M+H]=497.0; Calc'd 496.5 for C30H20N6O2.

Workup

  1. customIn a nitrogen purged
  2. customsealed tube
  3. addition1,4-dioxane (1.4 mL) was added
  4. customthe tube was purged with nitrogen for 5 min
  5. customsealed
  6. customThe tube was purged with nitrogen
  7. customsealed
  8. temperatureto cool to RT
  9. concentrationwas concentrated in vacuo
  10. customThe crude material was purified by silica gel chromatography
  11. customThe remaining impurities were removed
  12. additionby diluting the crude with methanol causing a light yellow solid
  13. customto precipitate
  14. filtrationwhich were filtered
  15. customair dried

Sources & evidence

ORD record
ord-f5d81c005a2f47eaad5b25343bd380fc
Source dataset
uspto-grants-2013_10
Patent number
US08557816B2

Reaction notes

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