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

HRID 1396556Notes

Reaction equation

HRID 1396556 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.CC1(C)C(C)(C)OB([C:21]2[CH:22]=[C:23]([C:28]([F:31])([F:30])[F:29])[C:24]([NH2:27])=[N:25][CH:26]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.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>[NH2:27][C:24]1[N:25]=[CH:26][C:21]([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:22][C:23]=1[C:28]([F:31])([F:29])[F:30]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 468641035-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-amine2×HCID 689626923-Bromo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine2×

Product 1

HCID 689614863-(6-Amino-5-trifluoromethyl-pyridin-3-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

3-Bromo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine (Intermediate 3) (0.1 g, 0.438 mmol), tetrakis(triphenylphosphine)palladium (0.031 g, 0.027 mmol), 5-(4,4,5,5-tetra methyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-pyridin-2-ylamine (Intermediate 10) (0.135 g, 0.669 mmol), cesium carbonate (0.290 g, 0.892 mmol) and water (1 ml) are suspended in 1,4-dioxane (4 ml) and heated using microwave radiation at 150° C. for 45 minutes. The reaction mixture is cooled to room temperature, filtered through Celite® (filter agent) and washed with EtOAc. The solvents are removed in vacuo and purification of the crude residue by flash chromatography on silica eluting with iso-hexanes:EtOAc (2:1) results in an off white solid. The solid is further purified by recrystallisation from 1:1 MeOH/EtOAc resulting in a white solid which is collected by filtration and dried under vacuum to afford the title compound.

Workup

  1. temperatureheated
  2. customat 150° C.
  3. customfor 45 minutes
  4. filtrationfiltered through Celite® (filter agent)
  5. washwashed with EtOAc
  6. customThe solvents are removed in vacuo and purification of the crude residue by flash chromatography on silica eluting with iso-hexanes:EtOAc (2:1)
  7. customresults in an off white solid
  8. customThe solid is further purified by recrystallisation from 1:1 MeOH/EtOAc resulting in a white solid which
  9. filtrationis collected by filtration
  10. customdried under vacuum

Sources & evidence

ORD record
ord-a5e79532caf74bb08795440f645ec9e4
Source dataset
uspto-grants-2014_12
Patent number
US08901134B2

Reaction notes

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