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}propanediamide

HRID 657297Notes

Reaction equation

HRID 657297 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:9][NH:10][C:11](=[O:37])[CH2:12][C:13]([NH:15][CH2:16][C:17]2[C:18]([NH:30][CH:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[C:19]3[CH:27]=[N:26][N:25]([CH2:28][CH3:29])[C:20]3=[N:21][C:22]=2[CH2:23][CH3:24])=[O:14])[CH:5]=[CH:6][C:7]=1[Cl:8].[CH:38]([C:40]1[CH:41]=[C:42](B(O)O)[CH:43]=[CH:44][CH:45]=1)=[O:39].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:44]2[CH:43]=[CH:42][CH:41]=[C:40]([CH:38]=[O:39])[CH:45]=2)=[CH:3][C:4]([CH2:9][NH:10][C:11](=[O:37])[CH2:12][C:13]([NH:15][CH2:16][C:17]2[C:18]([NH:30][CH:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[C:19]3[CH:27]=[N:26][N:25]([CH2:28][CH3:29])[C:20]3=[N:21][C:22]=2[CH2:23][CH3:24])=[O:14])=[CH:5][CH:6]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343563-Formylphenylboronic acidHCID 57819878N-[(3-bromo-4-chlorophenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}propanediamide

Product 1

HCID 57819914N-[(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}propanediamideYield 68.1%

Reagents, catalysts & solvents 4

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

Procedure

A mixture 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}propanediamide (1.06 g, 1.791 mmol), (3-formylphenyl)boronic acid (0.330 g, 2.2 mmol), tetrakis (triphenylphosphine) palladium (0) (0.092 g, 0.08 mmol), sodium carbonate (0.212 g, 2.0 mmol) in 1,4-dioxane (12 mL) and water (4 mL) was microwaved at 140° C. for 30 min. The reaction mixture was diluted with water and EtOAc; layers were separated. The aqueous phase was re-extracted with EtOAc. The combined organic extracts were dried over Na2SO4 and evaporated to a residue. This residue 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}propanediamide (752.4 mg, 68.1%) as a glassy solid. LC-MS m/z 617.3 (M+H)+, 0.86 min (ret time).

Workup

  1. customwas microwaved at 140° C. for 30 min
  2. customlayers were separated
  3. extractionThe aqueous phase was re-extracted with EtOAc
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. customevaporated to a residue
  6. customThis residue was purified on the Chromatotron on silica gel (2000u)
  7. washeluting with CH2Cl2 (3-6% MeOH)

Sources & evidence

ORD record
ord-6ec08d4f3a9744bf96d0f7c62c50307a
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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