Sodium Carbonate → HCID 58158324, compound

HRID 2368822Notes

Reaction equation

HRID 2368822 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[N:14]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[CH3:31])[C:15](=[O:24])[C:16]4[C:17]([CH3:23])=[CH:18][CH:19]=[N:20][C:21]=4[CH:22]=3)[N:9]=[C:10](I)[C:3]=12.[OH:32][C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C(O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[N:14]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[CH3:31])[C:15](=[O:24])[C:16]4[C:17]([CH3:23])=[CH:18][CH:19]=[N:20][C:21]=4[CH:22]=3)[N:9]=[C:10]([C:37]3[CH:36]=[CH:35][CH:34]=[C:33]([OH:32])[CH:38]=3)[C:3]=12

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 58158296HCID 58158296, compound

Product 1

HCID 58158324HCID 58158324, compoundYield 69.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 86633292ethanol water DMFSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred mixture of 7-((4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-4-methyl-6-o-tolyl-1,6-naphthyridin-5(6H)-one (2114) (1.05 g, 2.0 mmol) and 3-hydroxyphenylboronic acid (0.33 g, 2.4 mmol) in DMF-EtOH—H2O (3:1:1, 50 mL), Pd(OAc)2 (0.14 g, 0.60 mmol), PPh3 (0.31 g, 1.2 mmol) and Na2CO3 (1.06 g, 10.0 mmol) were added sequentially. The resulting mixture was degassed and back-filled with argon three times and then stirred at 80° C. for 1 h. The mixture was allowed to cool to RT, filtered through silica gel (5 g) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (2-5% MeOH/DCM) to afford the desired product, 7-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-4-methyl-6-o-tolyl-1,6-naphthyridin-5(6H)-one (2115) (0.68 g, 69% yield) as a slight yellow solid. Then the product was dissolved in EtOH (5 mL), and stirred at reflux for 30 min. The solution was allowed to cool to RT and the solid was collected by filtration. The solid was then suspended in ethyl acetate (5 mL), and stirred at RT for 16 h. The precipitate was collected by filtration and further dried in vacuo to afford the desired product, 7-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-4-methyl-6-o-tolyl-1,6-naphthyridin-5(6H)-one (2115) (0.59 g, 60% yield) as a white solid.

Workup

  1. additionwere added sequentially
  2. customThe resulting mixture was degassed
  3. additionback-filled with argon three times
  4. temperatureto cool to RT
  5. filtrationfiltered through silica gel (5 g)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel (2-5% MeOH/DCM)

Sources & evidence

ORD record
ord-1a2841ee48cc42208bc4e7909e6a364f
Source dataset
uspto-grants-2014_04
Patent number
US08703777B2

Reaction notes

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