Water → HCID 178461595, compound

HRID 522814Notes

Reaction equation

HRID 522814 reaction equation
Br[C:2]1[NH:3][C:4]2[C:9]([N:10]=1)=[C:8]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][C@H:12]1[CH3:17])[N:7]=[C:6]([N:18]1[CH2:23][CH2:22][O:21][CH2:20][C@H:19]1[CH3:24])[N:5]=2.O.[NH:26]1[CH:30]=[CH:29][N:28]=[C:27]1[C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.[F-].[Cs+]>C(#N)C.C(Cl)Cl.C(O)(C)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:26]1[CH:30]=[CH:29][N:28]=[C:27]1[C:31]1[CH:36]=[CH:35][C:34]([C:2]2[NH:3][C:4]3[C:9]([N:10]=2)=[C:8]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][C@H:12]2[CH3:17])[N:7]=[C:6]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][C@H:19]2[CH3:24])[N:5]=3)=[CH:33][CH:32]=1

Participants

9

Reactant 4

HCID 962WaterHCID 25953Cesium fluorideHCID 66575043(4-(1H-Imidazol-2-yl)phenyl)boronic acidHCID 178461594HCID 178461594, compound

Product 1

HCID 178461595HCID 178461595, compoundYield 50.4%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 3776IsopropanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

8-Bromo-2,6-bis-((R)-3-methyl-morpholin-4-yl)-9H-purine (99 mg, 250 μmol) was dissolved in 2 mL of acetonitrile and 0.2 mL of water under argon. 4-(1H-imidazol-2-yl)phenyl boronic acid (58.7 mg, 313 μmol), CsF (57 mg, 375 μmol), and Pd(PPh3)4 (28.9 mg, 25 μmol) were added. The suspension was stirred at 50° C. for 10 minutes in a closed microwave vial. Then it was irradiated for 40 minutes in a microwave apparatus at 150° C. The vial was cooled and uncapped, and the reaction mixture was diluted with 50 mL of CH2Cl2 and 10 mL of isopropanol. The organic solvents were washed with brine and aqueous NaHCO3, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (40 g SiO2, CH2Cl2/EtOH/aqueous NH3 in a gradient from 100/0/0.1 to 90/10/0.1) to give the product as a solid (58 mg, 48%).

Workup

  1. customThen it was irradiated for 40 minutes in a microwave apparatus at 150° C
  2. temperatureThe vial was cooled
  3. washThe organic solvents were washed with brine and aqueous NaHCO3
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography (40 g SiO2, CH2Cl2/EtOH/aqueous NH3 in a gradient from 100/0/0.1 to 90/10/0.1)

Sources & evidence

ORD record
ord-6a5c567c6cf84e85a83f7265ee75d0bc
Source dataset
uspto-grants-2016_05
Patent number
US09334271B2

Reaction notes

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