Dichloromethane → 5-[6-(2,6-difluoro-3,5-dimethoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-N,N-dimethyl-2,3-dihydro-1-benzofuran-2-carboxamide

HRID 1778657Notes

Reaction equation

HRID 1778657 reaction equation
[F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([F:12])[C:3]=1[C:13]1[N:18]=[C:17]2[NH:19][N:20]=[C:21](I)[C:16]2=[CH:15][N:14]=1.[CH3:23][N:24]([CH3:45])[C:25]([CH:27]1[CH2:31][C:30]2[CH:32]=[C:33](B3OC(C)(C)C(C)(C)O3)[CH:34]=[CH:35][C:29]=2[O:28]1)=[O:26].ClCCl.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([F:12])[C:3]=1[C:13]1[N:18]=[C:17]2[NH:19][N:20]=[C:21]([C:33]3[CH:34]=[CH:35][C:29]4[O:28][CH:27]([C:25]([N:24]([CH3:23])[CH3:45])=[O:26])[CH2:31][C:30]=4[CH:32]=3)[C:16]2=[CH:15][N:14]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 86722799N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1-benzofuran-2-carboxamideHCID 178493522HCID 178493522, compound

Product 1

HCID 1784935005-[6-(2,6-difluoro-3,5-dimethoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-N,N-dimethyl-2,3-dihydro-1-benzofuran-2-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-(2,6-difluoro-3,5-dimethoxyphenyl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidine (15.0 mg, 0.0359 mmol), N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1-benzofuran-2-carboxamide (13.6 mg, 0.0430 mmol) (Peak I), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (1.8 mg, 0.0022 mmol) and potassium phosphate (22.8 mg, 0.108 mmol) in 1,4-dioxane (0.48 mL) and water (0.24 mL) in a reaction vial was sealed, and degassed and recharged with nitrogen for three times. The mixture was stirred at 100° C. overnight. After cooling, the mixture was diluted with methanol, and purified by RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+=482.1.

Workup

  1. customin a reaction
  2. customvial was sealed
  3. customdegassed
  4. temperatureAfter cooling
  5. additionthe mixture was diluted with methanol
  6. custompurified by RP-HPLC (pH=10)

Sources & evidence

ORD record
ord-595bd3fd645146b18e49b5cb5000947c
Source dataset
uspto-grants-2016_02
Patent number
US09266892B2

Reaction notes

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