Potassium Carbonate → HCID 71621380, compound

HRID 2278844Notes

Reaction equation

HRID 2278844 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].[F:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[N:31][CH:32]=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:29]3[CH:30]=[N:31][CH:32]=[C:27]([F:26])[CH:28]=3)=[C:3]([NH2:25])[N:4]=2)=[N:9]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 75806TricyclohexylphosphineHCID 44717403(5-Fluoropyridin-3-yl)boronic acidHCID 89690930HCID 89690930, compound

Product 1

HCID 71621380HCID 71621380, compoundYield 77.4%

Reagents, catalysts & solvents 2

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

Procedure

Under an argon atmosphere, 100 mg (purity 65%, 0.183 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 4 ml of absolute dioxane. 103 mg (0.731 mmol) of (5-fluoropyridin-3-yl)boronic acid and 25 mg (0.183 mmol) of potassium carbonate were added and argon was passed through the suspension for 10 min with stirring. Then, 3 mg (4.020 mol) of 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) chloride were added and again argon was passed through the mixture for 1 min. The reaction mixture was stirred for 20 min in the microwave at 140° C. 5 mg (0.018 mmol) of tricyclohexylphosphine were added and the mixture was again stirred for 20 min in the microwave at 140° 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). 59 mg of the target compound were obtained (58% of theory).

Workup

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

Sources & evidence

ORD record
ord-c62a8dc62e0640f7b1dfe87a932ca746
Source dataset
uspto-grants-2015_09
Patent number
US09133191B2

Reaction notes

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