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

HRID 657304Notes

Reaction equation

HRID 657304 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[Cl: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>[Cl:8][C:7]1[C:2]([C:45]2[CH:44]=[CH:43][CH:42]=[C:41]([CH:39]=[O:40])[CH:46]=2)=[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]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343563-Formylphenylboronic acidHCID 57819887N-[(3-bromo-4-chlorophenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}butanediamide

Product 1

HCID 57819867N-[(6-chloro-3'-formyl-3-biphenylyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}butanediamideYield 83%

Reagents, catalysts & solvents 4

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

Procedure

A solution of N-[(3-bromo-4-chlorophenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}butanediamide (1.0 g, 1.650 mmol), (3-formylphenyl)boronic acid (0.300 g, 2.00 mmol), tetrakis (triphenylphosphine) palladium (0) (0.092 g, 0.08 mmol) and sodium carbonate (0.509 g, 4.8 mmol) in 1,4-dioxane (12 mL) and water (4.00 mL) was microwaved at 140° C. for 30 min. The reaction was diluted with water and EtOAc and the organic layer taken off. The aqueous phase was re-extracted with EtOAc. The combined organic layers were dried over Na2SO4 and solvent was evaporated giving a residue. The crude material was purified on the Chromatotron on silica gel (2000u) eluting with CH2Cl2 (3-6% MeOH) to give N-[(6-chloro-3′-formyl-3-biphenylyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}butanediamide (861 mg, 83%) as a glassy solid. LC-MS m/z 631.4 (M+H)+, 0.86 min (ret time).

Workup

  1. extractionThe aqueous phase was re-extracted with EtOAc
  2. dry with materialThe combined organic layers were dried over Na2SO4 and solvent
  3. customwas evaporated
  4. customgiving a residue
  5. customThe crude material was purified on the Chromatotron on silica gel (2000u)
  6. washeluting with CH2Cl2 (3-6% MeOH)

Sources & evidence

ORD record
ord-4316bb2f072a40368b1fab3817c68398
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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