Water → HCID 67492851, compound

HRID 384080Notes

Reaction equation

HRID 384080 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([C:15]3([CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:18][O:17][CH2:16]3)[CH:12]=[CH:13][CH:14]=2)O1.I[C:30]1[CH:35]=[CH:34][N:33]=[C:32]2[N:36]([C:43]([C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[N:37]=[C:38]([C:39]([F:42])([F:41])[F:40])[C:31]=12.C(=O)([O-])[O-].[Na+].[Na+].O>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.C(OCC)(=O)C>[F:40][C:39]([F:42])([F:41])[C:38]1[C:31]2[C:32](=[N:33][CH:34]=[CH:35][C:30]=2[C:9]2[CH:10]=[C:11]([C:15]3([CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:25])([CH3:24])[CH3:26])[CH2:16][O:17][CH2:18]3)[CH:12]=[CH:13][CH:14]=2)[N:36]([C:43]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[N:37]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 579697084-Iodo-3-(trifluoromethyl)-1-(triphenylmethyl)-1H-pyrazolo[3,4-b]pyridineHCID 57969842HCID 57969842, compound

Product 1

HCID 67492851HCID 67492851, compoundYield 50.3%

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

tert-Butyl N-[[3-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]oxetan-3-yl]methyl]carbamate (65 mg, 0.1670 mmol) was dissolved in dioxane (3 mL) and 4-iodo-3-(trifluoromethyl)-1-trityl-pyrazolo[3,4-b]pyridine (92.74 mg, 0.1670 mmol) was added followed by sodium carbonate (250.5 μL of 2 M, 0.5010 mmol). The reaction was degassed and filled with nitrogen 5 times then Pd[P(tBu)3]2 (12.80 mg, 0.02505 mmol) was added. The reaction was heated at 60° C. overnight. After cooling, water was added followed by ethyl acetate. The aqueous layer was extracted three times with ethyl acetate, the combined organics washed with brine, dried over MgSO4, filtered and the solvent removed under reduced pressure. The crude product was purified on silica (Companion, 12 g) eluting with 2.5-50% EtOAc:Pet.ether to give tert-butyl N-[[3-[3-[3-(trifluoromethyl)-1-trityl-pyrazolo[3,4-b]pyridin-4-yl]phenyl]oxetan-3-yl]methyl]carbamate as a white foam (58 mg, 50%).

Workup

  1. customThe reaction was degassed
  2. additionfilled with nitrogen 5 times
  3. temperatureAfter cooling
  4. extractionThe aqueous layer was extracted three times with ethyl acetate
  5. washthe combined organics washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customThe crude product was purified on silica (Companion, 12 g)
  10. washeluting with 2.5-50% EtOAc

Sources & evidence

ORD record
ord-2bca417729a540b1ada950ff920ce014
Source dataset
uspto-grants-2013_02
Patent number
US08367697B2

Reaction notes

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