1,4-Dioxane → 2-Chloro-5-(1-methyl-1H-pyrazol-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine

HRID 529659Notes

Reaction equation

HRID 529659 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([O:20][CH:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:5]2[C:10](I)=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:6]=2[N:7]=1.[CH3:27][N:28]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[N:29]1.O1CCOCC1>O>[Cl:1][C:2]1[N:3]=[C:4]([O:20][CH:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:5]2[C:10]([C:31]3[CH:30]=[N:29][N:28]([CH3:27])[CH:32]=3)=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 867264332-Chloro-5-iodo-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 867264342-Chloro-5-(1-methyl-1H-pyrazol-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidineYield 88%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

To a degassed mixture of 2-chloro-5-iodo-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.1 equiv) and potassium phosphate tribasic trihydrate (3 equiv) in a 10:1 mixture of 1,4-dioxane and water (0.09 M)) was added palladium 1,1-bis(diphenylphosphion)ferrocene dichloride (0.2 equiv). The mixture was stirred at 110° C. for 2 h. The suspension was cooled to room temperature and filtered. The filtrate was concentrated and the residue obtained was purified by silica gel chromatography (20% ethyl acetate in petroleum ether) to afford the title compound (88% yield). MS (ESI) m/z=464.1 [M+1]+.

Workup

  1. temperatureThe suspension was cooled to room temperature
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. customthe residue obtained
  5. customwas purified by silica gel chromatography (20% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-eef997e80f0e48c1bab8ae81b7de194d
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

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