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

HRID 564419Notes

Reaction equation

HRID 564419 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][NH:9][C:10]([C:12]2[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]([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:13]=2)=[O:11])[CH:5]=[CH:6][CH:7]=1.[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:14]3[CH:15]=[C:16]([CH3:18])[CH:17]=[C:12]([C:10]([NH:9][CH2:8][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)[CH:7]=[CH:6][CH:5]=4)=[O:11])[CH:13]=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 57813471N-[(3-bromophenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-5-methyl-1,3-benzenedicarboxamide

Product 1

HCID 57813328N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(3'-formyl-3-biphenylyl)methyl]-5-methyl-1,3-benzenedicarboxamideYield 67.2%

Reagents, catalysts & solvents 4

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

Procedure

N-[(3-Bromophenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-5-methyl-1,3-benzenedicarboxamide (0.825 g, 1.302 mmol), (3-formylphenyl)boronic acid (0.195 g, 1.302 mmol), potassium carbonate (0.540 g, 3.91 mmol), and Pd(Ph3P)4 (0.075 g, 0.065 mmol) were divided into 3 portions and added to three 2-5 mL Biotage microwave vials in 1,4-dioxane (3 mL) and water (1 mL). The vials were capped and the mixtures were microwaved at normal power in the Emrys Optimizer at 100° C. for 15 min. The combined crude product was partitioned between EtOAc (75 mL) and water (20 mL). The phases were separated, and the organic phase was washed with water (2×20 mL), brine (20 mL), dried over anhydrous Na2SO4 filtered and evaporated to give the crude residue. The residue was taken up in DCM and absorbed on Isolute® Sorbent and purified by Combiflash using an 80 g silica column eluted with 0-10% DCM/MeOH. The product fractions were combined and concentrated to give (N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(3′-formyl-3-biphenylyl)methyl]-5-methyl-1,3-benzenedicarboxamide (584.1 mg, 0.875 mmol, 67.2% yield)) as a white solid. LC-MS m/z 659.6 (M+H)+, 1.01 min (ret time); mp 109-112° C.

Workup

  1. customThe vials were capped
  2. customthe mixtures were microwaved at normal power in the Emrys Optimizer at 100° C. for 15 min
  3. customwas partitioned between EtOAc (75 mL) and water (20 mL)
  4. customThe phases were separated
  5. washthe organic phase was washed with water (2×20 mL), brine (20 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customto give the crude residue
  10. customabsorbed on Isolute® Sorbent
  11. custompurified by Combiflash
  12. washeluted with 0-10% DCM/MeOH
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-5427947fa65243678b8929e5e05b5c5f
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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