Dichloromethane → 6-(3,5-dimethoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine

HRID 1778649Notes

Reaction equation

HRID 1778649 reaction equation
Cl[C:2]1[N:7]=[C:6]2[N:8]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[N:9]=[CH:10][C:5]2=[CH:4][N:3]=1.[CH3:17][O:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[C:23]([O:25][CH3:26])[CH:24]=1.ClCCl.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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]>[CH3:17][O:18][C:19]1[CH:20]=[C:21]([C:2]2[N:7]=[C:6]3[N:8]([CH:11]4[CH2:16][CH2:15][CH2:14][CH2:13][O:12]4)[N:9]=[CH:10][C:5]3=[CH:4][N:3]=2)[CH:22]=[C:23]([O:25][CH3:26])[CH:24]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 4374257(3,5-Dimethoxyphenyl)boronic acidHCID 867228006-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine

Product 1

HCID 867228016-(3,5-dimethoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (5.2 mmol), (3,5-dimethoxyphenyl)boronic acid (1.0 g, 5.7 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complexed with dichloromethane (1:1) (0.3 g, 0.4 mmol) and potassium phosphate (2.2 g) in 1,4-dioxane (10 mL) and water (2 mL) in a reaction vial was degassed and sealed. The mixture was stirred at 100° C. for 3 h. After cooling, the reaction mixture was extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-35%) to afford the desired product. LCMS (M+H)+=341.1.

Workup

  1. customvial was degassed
  2. customsealed
  3. temperatureAfter cooling
  4. extractionthe reaction mixture was extracted with ethyl acetate (3×20 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-35%)

Sources & evidence

ORD record
ord-28856244622a4107be26e1e938257f3b
Source dataset
uspto-grants-2016_02
Patent number
US09266892B2

Reaction notes

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