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-(methyloxy)-3-biphenylyl]methyl}butanediamide

HRID 657306Notes

Reaction equation

HRID 657306 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:10][NH:11][C:12](=[O:39])[CH2:13][CH2:14][C:15]([NH:17][CH2:18][C:19]2[C:20]([NH:32][CH:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[C:21]3[CH:29]=[N:28][N:27]([CH2:30][CH3:31])[C:22]3=[N:23][C:24]=2[CH2:25][CH3:26])=[O:16])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[CH:40]([C:42]1[CH:43]=[C:44](B(O)O)[CH:45]=[CH:46][CH:47]=1)=[O:41].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>[CH2:30]([N:27]1[C:22]2=[N:23][C:24]([CH2:25][CH3:26])=[C:19]([CH2:18][NH:17][C:15](=[O:16])[CH2:14][CH2:13][C:12]([NH:11][CH2:10][C:4]3[CH:3]=[C:2]([C:46]4[CH:45]=[CH:44][CH:43]=[C:42]([CH:40]=[O:41])[CH:47]=4)[C:7]([O:8][CH3:9])=[CH:6][CH:5]=3)=[O:39])[C:20]([NH:32][CH:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[C:21]2[CH:29]=[N:28]1)[CH3:31]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343563-Formylphenylboronic acidHCID 57819893N-{[3-bromo-4-(methyloxy)phenyl]methyl}-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}butanediamide

Product 1

HCID 57819892N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-{[3'-formyl-6-(methyloxy)-3-biphenylyl]methyl}butanediamideYield 69.8%

Reagents, catalysts & solvents 4

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

Procedure

A mixture of N-{[3-bromo-4-(methyloxy)phenyl]methyl}-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}butanediamide (0.964 g, 1.603 mmol), (3-formylphenyl)boronic acid (0.300 g, 2.0 mmol), tetrakis (triphenylphosphine) palladium (0) (0.081 g, 0.07 mmol), and sodium carbonate (0.477 g, 4.5 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. The organic layers separated. The organic layer was washed with saturated NaCl, and then dried over Na2SO4. The organic layer was evaporated to viscous taffy. The viscous taffy 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-(methyloxy)-3-biphenylyl]methyl}butanediamide (701 mg, 69.8%) as a viscous, nearly colorless, taffy. LC-MS m/z 627.5 (M+H)+, 0.81 min (ret time).

Workup

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

Sources & evidence

ORD record
ord-628e76fa31274cd9aa915fdaab863419
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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