Sodium Carbonate → HCID 68253483, compound

HRID 2405893Notes

Reaction equation

HRID 2405893 reaction equation
[CH2:1]([O:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]2[N:10]([C:14]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:11]=[C:12](I)[C:5]=12)[CH3:2].[F:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[N:35]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH2:1]([O:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]2[N:10]([C:14]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:11]=[C:12]([C:36]3[CH:37]=[CH:38][CH:39]=[C:34]([F:33])[N:35]=3)[C:5]=12)[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 426145762-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 68253447HCID 68253447, compound

Product 1

HCID 68253483HCID 68253483, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

4-ethoxy-3-iodo-1-trityl-pyrazolo[3,4-d]pyrimidine (590 mg, 1.11 mmol), 2-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (296.7 mg, 1.33 mmol) and Na2CO3 (1.662 mL of 2 M, 3.324 mmol) were suspended in anhydrous Dioxane (25 mL) and degassed (vacuum/nitrogen cycles×5). Pd[P(tBu)3]2 (56.62 mg, 0.11 mmol) was added and the reaction mixture was degassed again (vacuum/nitrogen cycles×5) and stirred at 60° C. for 3 hours. After this time, the reaction mixture was allowed to cool to ambient temperature. DCM, saturated aqueous Na2CO3 and brine were added and the aqueous layer was extracted with DCM (4×50 mL). The combined organics were dried (Na2SO4), filtered and concentrated in vacuo. The crude mixture was purified by column chromatography (ISCO Companion™, 120 g column, eluting with EtOAc/petroleum ether) to give the sub title compound (139.1 mg, 25% Yield). 1H NMR (400 MHz, DMSO) δ 8.17 (1H, s), 7.77 (1H, m), 7.63 (1H, m), 7.24-7.11 (15H, m), 6.89-6.81 (1H, m), 4.50 (2H, q) and 1.44 (3H, t).

Workup

  1. customdegassed (vacuum/nitrogen cycles×5)
  2. customthe reaction mixture was degassed again (vacuum/nitrogen cycles×5)
  3. temperatureto cool to ambient temperature
  4. additionDCM, saturated aqueous Na2CO3 and brine were added
  5. extractionthe aqueous layer was extracted with DCM (4×50 mL)
  6. dry with materialThe combined organics were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude mixture was purified by column chromatography (ISCO Companion™, 120 g column, eluting with EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-17b57946bbf54f5792fadc4ad009c361
Source dataset
uspto-grants-2014_08
Patent number
US08809335B2

Reaction notes

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