Water → N-(3-(4-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)phenyl)-3-methylbut-2-enamide

HRID 570785Notes

Reaction equation

HRID 570785 reaction equation
[CH3:1][C:2]([CH3:22])=[CH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9](B2OC(C)(C)C(C)(C)O2)[CH:8]=1)=[O:5].I[C:24]1[C:28]([CH:29]=[O:30])=[CH:27][N:26]([CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][O:32]2)[N:25]=1.C([O-])(O)=O.[Na+].O>O1CCOCC1.CO.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:29]([C:28]1[C:24]([C:9]2[CH:8]=[C:7]([NH:6][C:4](=[O:5])[CH:3]=[C:2]([CH3:1])[CH3:22])[CH:12]=[CH:11][CH:10]=2)=[N:25][N:26]([CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][O:32]2)[CH:27]=1)=[O:30]

Participants

8

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 904242893-Iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-carbaldehydeHCID 904257663-methyl-N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)but-2-enamide

Product 1

HCID 90425471N-(3-(4-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)phenyl)-3-methylbut-2-enamideYield 73.43%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 3-methyl-N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)but-2-enamide (0.261 g, 0.00098 mol) and 3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-carbaldehyde (0.250 g, 0.000817 mol) in 1,4-dioxane (8 ml) was added saturated NaHCO3 solution (8 mL). The reaction mixture was degassed using argon for 0.5 h. Tetrakis(triphenylphosphine) palladium (0.094 g, 0.000081 mol) was added under an argon atm. and the resultant suspension was heated for 8 h at 90° C. The reaction was poured into water (50 mL) extracted with EtOAc (40 mL×2). The combined extracts were washed with brine (50 mL) dried over sodium sulphate and concentrated under vacuum. The residue was purified by SGC using DCM:MeOH (0-1%) as eluent to obtain N-(3-(4-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)phenyl)-3-methylbut-2-enamide (0.210 g, Yield 73.43%). LCMS (ESI): RT=2.20 min, m/z=354.3 [M+H]+.

Workup

  1. customThe reaction mixture was degassed
  2. customfor 0.5 h
  3. extractionextracted with EtOAc (40 mL×2)
  4. washThe combined extracts were washed with brine (50 mL)
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by SGC

Sources & evidence

ORD record
ord-5bd74064b9ca48d6ab93cfa4adf8b3fa
Source dataset
uspto-grants-2015_05
Patent number
US09023883B2

Reaction notes

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