Potassium Phosphate, Tribasic → HCID 86701076, compound

HRID 1916503Notes

Reaction equation

HRID 1916503 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([CH:11]=[O:12])=[N:9][N:8]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][O:14]3)[C:5]2=[N:6][CH:7]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[N:27]1[CH:32]=[CH:31][CH:30]=[C:29](B(O)O)[CH:28]=1>CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:2]2[CH:3]=[C:4]3[C:10]([CH:11]=[O:12])=[N:9][N:8]([CH:13]4[CH2:18][CH2:17][CH2:16][CH2:15][O:14]4)[C:5]3=[N:6][CH:7]=2)[CH:28]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acidHCID 583775865-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde

Product 1

HCID 86701076HCID 86701076, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a heterogeneous solution of 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde (III) (328 mg, 1.05 mmol) and K3PO4 (334 mg, 1.57 mmol) in DMF (10 mL) and water (2 mL) was added pyridin-3-ylboronic acid (143 mg, 1.16 mmol). The solution was purged with argon by using argon/vacuum cycle (3×). Pd(PPh3)4 (36 mg, 0.03 mmol) was added to the solution and again purged with argon. The solution was heated at 90° C. for 4 h under argon. The DMF was removed under vacuum. The residue was partitioned between EtOAc and water. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined EtOAc was dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified through a silica gel column (10:90 EtOAc:hexane→50:50 EtOAc:hexane) to produce 5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde (CXXXI) as an off-white waxy solid (283 mg, 0.92 mmol, 91% yield). 1H NMR (DMSO-d6) δ ppm 1.57-1.68 (m, 3H), 1.75-1.89 (m, 1H), 2.01-2.13 (m, 2H), 2.49-2.56 (m, 1H), 3.78 (dt, J=11 Hz, J=4 Hz, 1H), 3.94-4.03 (m, 1H), 6.25 (dd, J=10 Hz, J=2 Hz, 1H), 7.58-7.64 (m, 1H), 8.25 (td, J=8 Hz, J=2 Hz, 1H), 8.66 (dd, J=5 Hz, J=2 Hz, 1H), 8.77 (d, J=2 Hz, 1H), 9.02 (d, J=2 Hz, 1H), 9.09 (d, J=2 Hz, 1H), 10.21 (s, 1H); ESIMS found for C17H16N4O2 m/z 309.4 (M+H).

Workup

  1. customThe solution was purged with argon
  2. customagain purged with argon
  3. customThe DMF was removed under vacuum
  4. customThe residue was partitioned between EtOAc and water
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with EtOAc
  7. dry with materialThe combined EtOAc was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified through a silica gel column (10:90 EtOAc:hexane→50:50 EtOAc:hexane)

Sources & evidence

ORD record
ord-02a4734d01db47b693fea55b7cdfd4af
Source dataset
uspto-grants-2013_12
Patent number
US08618128B1

Reaction notes

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