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

HRID 564666Notes

Reaction equation

HRID 564666 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])[CH:14]=2)=[O:12])[CH:5]=[CH:6][C:7]=1[F:8].CC1(C)C(C)(C)OB([C:51]2[CH:52]=[C:53]([CH2:57][CH:58]3[CH2:63][CH2:62][N:61](C(OC(C)(C)C)=O)[CH2:60][CH2:59]3)[CH:54]=[CH:55][CH:56]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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>[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:55]5[CH:56]=[CH:51][CH:52]=[C:53]([CH2:57][CH:58]6[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]6)[CH:54]=5)[C:7]([F:8])=[CH:6][CH:5]=4)=[O:12])[CH: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

7

Reactant 3

HCID 11430Potassium CarbonateHCID 57813256N-[(3-Bromo-4-fluorophenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamideHCID 578134461,1-Dimethylethyl 4-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}-1-piperidinecarboxylate

Product 1

HCID 44181204N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-{[6-fluoro-3'-(4-piperidinylmethyl)-3-biphenylyl]methyl}-1,3-benzenedicarboxamideYield 21.9%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of N-[(3-bromo-4-fluorophenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide (0.641 g, 0.1 mmol) in 1,4-dioxane (1.5 ml) and water (0.500 ml) was added 1,1-dimethylethyl 4-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}-1-piperidinecarboxylate (0.048 g, 0.120 mmol), Pd(Ph3P)4 (4.62 mg, 4.00 μmol), and K2CO3 (0.041 g, 0.300 mmol). This mixture was heated using a microwave instrument at 150° C. for 15 min. The organic layer was separated, concentrated using a Glas-Col evaporator, purified using a Gilson HPLC (with TFA), concentrated by GeneVav EZ-2 evaporator. The resulting solid was added to DCM (0.3 mL) then TFA (0.15 mL) and this mixture was left stand for 30 min before it was concentrated using a Glas-Col evaporator. The concentrate was purified using a Gilson HPLC (with TFA), concentrated by GeneVav EZ-2 evaporator, basified by amine cartridge to afford the title compound 0.016 g (21%). LC-MS m/z 732 (M+H)+.

Workup

  1. temperatureThis mixture was heated
  2. customat 150° C.
  3. customfor 15 min
  4. customThe organic layer was separated
  5. concentrationconcentrated
  6. customa Glas-Col evaporator
  7. custompurified
  8. concentrationconcentrated by GeneVav EZ-2 evaporator
  9. additionThe resulting solid was added to DCM (0.3 mL)
  10. concentrationwas concentrated
  11. customa Glas-Col evaporator
  12. customThe concentrate was purified
  13. concentrationconcentrated by GeneVav EZ-2 evaporator

Sources & evidence

ORD record
ord-c1b55d61b05c47c08d4f039ee3a3304d
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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