Potassium Carbonate → N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(3'-formyl-6-methyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamide

HRID 662090Notes

Reaction equation

HRID 662090 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:9][NH:10][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([NH:21][CH2:22][C:23]3[C:24]([NH:36][CH:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)=[C:25]4[CH:33]=[N:32][N:31]([CH2:34][CH3:35])[C:26]4=[N:27][C:28]=3[CH2:29][CH3:30])=[O:20])[N:14]=2)=[O:12])[CH:5]=[CH:6][C:7]=1[CH3:8].[CH:43]([C:45]1[CH:46]=[C:47](B(O)O)[CH:48]=[CH:49][CH:50]=1)=[O:44].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C(Cl)Cl.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>[CH2:34]([N:31]1[C:26]2=[N:27][C:28]([CH2:29][CH3:30])=[C:23]([CH2:22][NH:21][C:19]([C:15]3[CH:16]=[CH:17][CH:18]=[C:13]([C:11]([NH:10][CH2:9][C:4]4[CH:3]=[C:2]([C:49]5[CH:48]=[CH:47][CH:46]=[C:45]([CH:43]=[O:44])[CH:50]=5)[C:7]([CH3:8])=[CH:6][CH:5]=4)=[O:12])[N:14]=3)=[O:20])[C:24]([NH:36][CH:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)=[C:25]2[CH:33]=[N:32]1)[CH3:35]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 27343563-Formylphenylboronic acidHCID 57819372N-[(3-bromo-4-methylphenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamide

Product 1

HCID 57819380N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(3'-formyl-6-methyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamideYield 93%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

N-[(3-Bromo-4-methylphenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamide (1.86 g, 2.93 mmol), (3-formylphenyl)boronic acid (0.439 g, 2.93 mmol), potassium carbonate (1.215 g, 8.79 mmol), and Pd(Ph3P)4 (0.169 g, 0.147 mmol) were combined in three 10-20 mL Biotage microwave vials in 1,4-dioxane (27 mL) and water (9 mL). The vials were capped and the mixture was heated in the microwave at normal power at 100° C. for 15 min. The crude product was partitioned between EtOAc (200 mL) and water (70 mL). The phases were separated, and the organic phase was washed with water (2×50 mL), brine (50 mL), dried over anhydrous Na2SO4, filtered and evaporated to give the crude residues. It was taken up in DCM and absorbed on Isolute® Sorbent and purified by a CombiFlash on a 120 g silica column eluted with 0-10% MeOH/DCM. Product fractions were combined and concentrated under vacuum to give (N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(3′-formyl-6-methyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamide (1.85 g, 2.72 mmol, 93% yield)) as a white solid. LC-MS m/z 660 (M+H)+, 0.94 min (ret time).

Workup

  1. customThe vials were capped
  2. customThe crude product was partitioned between EtOAc (200 mL) and water (70 mL)
  3. customThe phases were separated
  4. washthe organic phase was washed with water (2×50 mL), brine (50 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give the crude residues
  9. customabsorbed on Isolute® Sorbent
  10. custompurified by a CombiFlash on a 120 g silica column
  11. washeluted with 0-10% MeOH/DCM
  12. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-72a4948ab9e741c7b32c423e556c1371
Source dataset
uspto-grants-2011_12
Patent number
US08084449B2

Reaction notes

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