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]-5-methyl-1,3-benzenedicarboxamide

HRID 564426Notes

Reaction equation

HRID 564426 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:9][NH:10][C:11]([C:13]2[CH:18]=[C:17]([CH3:19])[CH:16]=[C:15]([C:20]([NH:22][CH2:23][C:24]3[C:25]([NH:37][CH:38]4[CH2:43][CH2:42][O:41][CH2:40][CH2:39]4)=[C:26]4[CH:34]=[N:33][N:32]([CH2:35][CH3:36])[C:27]4=[N:28][C:29]=3[CH2:30][CH3:31])=[O:21])[CH:14]=2)=[O:12])[CH:5]=[CH:6][C:7]=1[CH3:8].[CH:44]([C:46]1[CH:47]=[C:48](B(O)O)[CH:49]=[CH:50][CH:51]=1)=[O:45].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>[CH2:35]([N:32]1[C:27]2=[N:28][C:29]([CH2:30][CH3:31])=[C:24]([CH2:23][NH:22][C:20]([C:15]3[CH:16]=[C:17]([CH3:19])[CH:18]=[C:13]([C:11]([NH:10][CH2:9][C:4]4[CH:3]=[C:2]([C:50]5[CH:49]=[CH:48][CH:47]=[C:46]([CH:44]=[O:45])[CH:51]=5)[C:7]([CH3:8])=[CH:6][CH:5]=4)=[O:12])[CH:14]=3)=[O:21])[C:25]([NH:37][CH:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)=[C:26]2[CH:34]=[N:33]1)[CH3:36]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 27343563-Formylphenylboronic acidHCID 57813312N-[(3-bromo-4-methylphenyl)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 57813255N-{[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]-5-methyl-1,3-benzenedicarboxamideYield 60.8%

Reagents, catalysts & solvents 4

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

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}-5-methyl-1,3-benzenedicarboxamide (840 mg, 1.297 mmol), (3-formylphenyl)boronic acid (194 mg, 1.297 mmol), potassium carbonate (538 mg, 3.89 mmol), and Pd(Ph3P)4 (74.9 mg, 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 mixture was 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 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-6-methyl-3-biphenylyl)methyl]-5-methyl-1,3-benzenedicarboxamide (537 mg, 0.789 mmol, 60.8% yield)) as a white solid. LC-MS m/z 673.4 (M+H)+, 0.99 min (ret time); mp 117-120° C.

Workup

  1. customThe vials were capped
  2. customthe mixture was 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 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-d33c93c41ba24cb285434e71a3b4d9fc
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

Loading…