Water → HCID 123458513, compound

HRID 1056990Notes

Reaction equation

HRID 1056990 reaction equation
Br[C:2]1[C:7]2[N:8]([CH3:11])[CH:9]=[N:10][C:6]=2[C:5]([O:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[F:20])=[C:4]([C:21]2[C:22]3[CH:31]=[N:30][N:29]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[C:23]=3[C:24](=[O:28])[N:25]([CH3:27])[CH:26]=2)[CH:3]=1.[CH3:40][C:41]1(C)C(C)(C)OB(C=C)O1.ClCCl.C(=O)([O-])[O-].[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]>[F:20][C:14]1[CH:15]=[C:16]([F:19])[CH:17]=[CH:18][C:13]=1[O:12][C:5]1[C:6]2[N:10]=[CH:9][N:8]([CH3:11])[C:7]=2[C:2]([CH:40]=[CH2:41])=[CH:3][C:4]=1[C:21]1[C:22]2[CH:31]=[N:30][N:29]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[C:23]=2[C:24](=[O:28])[N:25]([CH3:27])[CH:26]=1

Participants

8

Reactant 6

HCID 962WaterHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 123392201HCID 123392201, compound

Product 1

HCID 123458513HCID 123458513, compoundYield 85.4%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
80 °C

Procedure

A mixture of 4-[7-bromo-4-(2,4-difluorophenoxy)-1-methyl-1H-benzimidazol-5-yl]-6-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one (0.0990 g, 0.160 mmol), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (0.0408 mL, 0.241 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.0131 g, 0.0160 mmol) and potassium carbonate (0.0555 g, 0.401 mmol) in 1,4-dioxane (1.0 mL, 12.8 mmol) and water (0.580 mL, 32.2 mmol) was degassed with nitrogen for 10 min, warmed to 80° C. and stirred at 80° C. for 2 h. The reaction mixture was diluted with water and ethyl acetate. Layers were separated and the organic layer was washed with brine, dried with sodium sulfate, filtered, and concentrated in vacuo to give a crude residue. Purification by flash column chromatography (100% hexanes to 100% EtOAc [EtOAc contained 5% MeOH]) gave the desired product (77 mg, 85%) as a white foam. LCMS calculated for C29H32F2N5O3Si (M+H)+: m/z=564.2. found: 564.1.

Workup

  1. customwas degassed with nitrogen for 10 min
  2. additionThe reaction mixture was diluted with water and ethyl acetate
  3. customLayers were separated
  4. washthe organic layer was washed with brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a crude residue
  9. customPurification by flash column chromatography (100% hexanes to 100% EtOAc [EtOAc contained 5% MeOH])

Sources & evidence

ORD record
ord-29755c2fd9d5406aa2553045c1efb8d7
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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