Potassium Carbonate → HCID 71621695, compound

HRID 2278852Notes

Reaction equation

HRID 2278852 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])[N:9]=2)=[N:4][C:3]=1[NH2:25].[CH3:26][C:27]1[CH:32]=[C:31](B(O)O)[CH:30]=[CH:29][N:28]=1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>O1CCOCC1.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]>[F:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[CH2:17][N:10]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:16]2[C:8]([C:5]2[N:6]=[N:7][C:2]([C:31]3[CH:30]=[CH:29][N:28]=[C:27]([CH3:26])[CH:32]=3)=[C:3]([NH2:25])[N:4]=2)=[N:9]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 75806TricyclohexylphosphineHCID 41926642-Methylpyridine-4-boronic acidHCID 89690930HCID 89690930, compound

Product 1

HCID 71621695HCID 71621695, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 312751,4-DioxaneSolvent

Procedure

Under an argon atmosphere, 140 mg (purity 65%, 0.256 mmol) of 6-chloro-3-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-1,2,4-triazine-5-amine were suspended in 5 ml of absolute dioxane. 105 mg (0.767 mmol) of (2-methylpyridin-4-yl)boronic acid, 1.023 ml (1.023 mmol) of 1N aqueous potassium carbonate solution and 14 mg (0.051 mmol) of tricyclohexylphosphine were added and argon was passed through the suspension for 10 min with stirring. Then, 28 mg (0.038 mmol) of 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) chloride were added and the reaction mixture was stirred for 30 min in the microwave at 140° C. Again, 19 mg (0.026 mmol) of 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) chloride were added and the reaction mixture was stirred for 40 min in the microwave at 150° C. After cooling, the mixture was filtered over an Extrelut cartridge and after-washed with a mixture of dichloromethane/methanol (v/v=20:1). The filtrate was concentrated and the residue was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 20:80→100:0). This gave 53 mg of the target compound (purity 92%; 41% of theory).

Workup

  1. stirringthe reaction mixture was stirred for 30 min in the microwave at 140° C
  2. stirringthe reaction mixture was stirred for 40 min in the microwave at 150° C
  3. temperatureAfter cooling
  4. filtrationthe mixture was filtered over an Extrelut cartridge
  5. washafter-washed with a mixture of dichloromethane/methanol (v/v=20:1)
  6. concentrationThe filtrate was concentrated
  7. customthe residue was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 20:80→100:0)

Sources & evidence

ORD record
ord-c6e6e32c83964d53b4c3e4c8eb72d19c
Source dataset
uspto-grants-2015_09
Patent number
US09133191B2

Reaction notes

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