Sodium 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]butanediamide

HRID 657308Notes

Reaction equation

HRID 657308 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:9][NH:10][C:11](=[O:38])[CH2:12][CH2:13][C:14]([NH:16][CH2:17][C:18]2[C:19]([NH:31][CH:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[C:20]3[CH:28]=[N:27][N:26]([CH2:29][CH3:30])[C:21]3=[N:22][C:23]=2[CH2:24][CH3:25])=[O:15])[CH:5]=[CH:6][C:7]=1[CH3:8].[CH:39]([C:41]1[CH:42]=[C:43](B(O)O)[CH:44]=[CH:45][CH:46]=1)=[O:40].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.CCOC(C)=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:29]([N:26]1[C:21]2=[N:22][C:23]([CH2:24][CH3:25])=[C:18]([CH2:17][NH:16][C:14](=[O:15])[CH2:13][CH2:12][C:11]([NH:10][CH2:9][C:4]3[CH:3]=[C:2]([C:45]4[CH:44]=[CH:43][CH:42]=[C:41]([CH:39]=[O:40])[CH:46]=4)[C:7]([CH3:8])=[CH:6][CH:5]=3)=[O:38])[C:19]([NH:31][CH:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[C:20]2[CH:28]=[N:27]1)[CH3:30]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343563-Formylphenylboronic acidHCID 57819894N-[(3-bromo-4-methylphenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}butanediamide

Product 1

HCID 57819918N-{[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]butanediamideYield 59%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 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}butanediamide (1.16 g, 1.981 mmol), (3-formylphenyl)boronic acid (0.372 g, 2.481 mmol), tetrakis (triphenylphosphine) palladium (0) (0.081 g, 0.07 mmol), and sodium carbonate (0.530 g, 5.00 mmol) in 1,4-dioxane (12 mL) and water (4 mL) under an N2 atmosphere was microwaved for 30 min at 140° C. The reaction mixture was diluted with EtOAc and water and the layers were separated. The organic layer was washed with saturated NaCl, dried over Na2SO4, and then evaporated giving a viscous taffy. It was purified on a Chromatotron Plate Silica Gel (1000μ) eluting with CH2Cl2— MeOH (97:3) to afford 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]butanediamide (713.9 mg, 47.1%) as a viscous, nearly colorless, foam, taffy. LC-MS m/z 611.5 (M+H)+, 0.86 min (ret time).

Workup

  1. customwas microwaved for 30 min at 140° C
  2. customthe layers were separated
  3. washThe organic layer was washed with saturated NaCl
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customgiving a viscous taffy
  7. customIt was purified on a Chromatotron Plate Silica Gel (1000μ)
  8. washeluting with CH2Cl2— MeOH (97:3)

Sources & evidence

ORD record
ord-01d0d6aeacbc4d65bd4e5d0655f2eb3a
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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