Water → 3-(5-Methanesulfonyl-pyridin-3-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine

HRID 1396568Notes

Reaction equation

HRID 1396568 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([NH2:11])=[N:8][CH:9]=2)[N:4]([CH3:12])[N:3]=1.[CH3:13][S:14]([C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[N:21][CH:22]=1)(=[O:16])=[O:15].C([O-])([O-])=O.[Na+].[Na+].O>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].CCOCC>[CH3:13][S:14]([C:17]1[CH:18]=[C:19]([C:2]2[C:10]3[C:5](=[N:6][C:7]([NH2:11])=[N:8][CH:9]=3)[N:4]([CH3:12])[N:3]=2)[CH:20]=[N:21][CH:22]=1)(=[O:16])=[O:15]

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 441193815-(Methylsulphonyl)pyridine-3-boronic acidHCID 689626923-Bromo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine2×

Product 1

HCID 689582303-(5-Methanesulfonyl-pyridin-3-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Procedure

3-Bromo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine (Intermediate 3) (150 mg, 0.66 mmol) and 5-(methylsulfonyl)pyridine-3-boronic acid (200 mg, 0.99 mmol) are suspended in 1,4-dioxane (4 ml). 2M aqueous Na2CO3 (1 ml) is added and the reaction mixture is degassed by bubbling argon through for 5 minutes. Pd(dppf)Cl2 (27 mg, 0.033 mmol) is added and the reaction mixture is heated using microwave radiation at 100° C. for 30 minutes. Water (20 ml) and Et2O (50 ml) are added to the reaction mixture and the resulting grey solid is collected by filtration washing further with water. The solid is suspended in MeOH and excess TFA is added until a solution forms. The organic solvent is reduced in vacuo and the crude residue is purified by reverse phase column chromatography (Isolute™ C18, water/acetonitrile, 0.1% TFA), the appropriate fractions are combined and concentrated in vacuo. The resulting solid is refluxed in EtOH, cooled to room temperature, filtered and dried under vacuum to afford the title compound.

Workup

  1. customthe reaction mixture is degassed
  2. customby bubbling argon through for 5 minutes
  3. temperaturethe reaction mixture is heated
  4. customat 100° C.
  5. customfor 30 minutes
  6. filtrationthe resulting grey solid is collected by filtration
  7. washwashing further with water
  8. additionexcess TFA is added until a solution forms
  9. customthe crude residue is purified by reverse phase column chromatography (Isolute™ C18, water/acetonitrile, 0.1% TFA)
  10. concentrationconcentrated in vacuo
  11. temperatureThe resulting solid is refluxed in EtOH
  12. filtrationfiltered
  13. customdried under vacuum

Sources & evidence

ORD record
ord-fe1c974e0b0c4cdcb6e2842cb773dfdd
Source dataset
uspto-grants-2014_12
Patent number
US08901134B2

Reaction notes

Loading…