Cesium carbonate → 3-(4-Benzyloxy-3-fluoro-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine

HRID 1396541Notes

Reaction equation

HRID 1396541 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.[CH2:13]([O:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][C:22]=1[F:30])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:13]([O:20][C:21]1[CH:26]=[CH:25][C:24]([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:23][C:22]=1[F:30])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 27377884-Benzyloxy-3-fluorophenylboronic AcidHCID 689626923-Bromo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine2×

Product 1

HCID 689679423-(4-Benzyloxy-3-fluoro-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

3-Bromo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine (Intermediate 3) (0.33 g, 1.46 mmol) and 4-benzyloxy-3-fluoro phenylboronic acid (0.43 g, 1.75 mmol) are suspended in 1,4-dioxane (5 ml) in a microwave vial flushed with argon. A solution of Cs2CO3 (1.43 g, 4.38 mmol) in water (1.5 ml) is added followed by Pd(PPh3)4 (0.085 g, 0.073 mmol) and the reaction mixture is heated using microwave radiation at 150° C. for 0.5 hours. After cooling to room temperature the reaction mixture is diluted with EtOAc (100 ml) and washed with saturated NaHCO3. The organic portion is dried over MgSO4, filtered, concentrated in vacuo and the resulting crude solid is triturated with EtOAc (˜20 ml) to afford the title compound as an off-white solid.

Workup

  1. customvial flushed with argon
  2. temperaturethe reaction mixture is heated
  3. customat 150° C.
  4. customfor 0.5 hours
  5. washwashed with saturated NaHCO3
  6. dry with materialThe organic portion is dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customthe resulting crude solid is triturated with EtOAc (˜20 ml)

Sources & evidence

ORD record
ord-a2f4f180d8404f908258af1f3259f704
Source dataset
uspto-grants-2014_12
Patent number
US08901134B2

Reaction notes

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