Potassium Carbonate → Lhd-221

HRID 1422476Notes

Reaction equation

HRID 1422476 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[N:3]=1.B(O)(O)[C:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[S:27][CH:26]=1.C(=O)([O-])[O-].[K+].[K+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.C(OCC)(=O)C.CC(N(C)C)=O>[S:27]1[CH:26]=[C:25]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[CH:7][N:8]3[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:14][CH2:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=3)[N:3]=2)[C:33]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]1=2

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 2776344(1-Benzothiophen-3-yl)boronic acidHCID 755299704-(2-((2-Chloro-9-isopropyl-9H-purin-6-yl)amino)ethyl)phenol

Product 1

HCID 46199207Lhd-221

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-(2-(2-chloro-9-isopropyl-9H-purin-6-ylamino)ethyl)phenol (950 g), thianaphthene-3-boronic acid (561 g), dichlorobis(triphenylphosphine)palladium(II) (10.1 g), potassium carbonate (791 g), water (3.25 L), and DMA (3.25 L) was stirred under a nitrogen atmosphere for 10 min. The stirred mixture was then heated at 70° C. for 14 h. Ethyl acetate (6.5 L) and water (3.25 L) were added, and the mixture was filtered through Celite (125 g) at 50° C., rinsing with ethyl acetate (1.0 L). The layers were separated, and the aqueous layer was extracted at 50° C. with additional ethyl acetate (7.5 L). The combined organic layers were washed with water (3×2.5 L), then distilled to remove about 2.5 L of solvent. Tetrahydrofuran (2.5 L) and silica bond thio silica gel (200 g) were added. The mixture was stirred at 70° C. for 16 hr, then was filtered, washing the pad with ethyl acetate (1.0 L). The combined filtrates were concentrated at atmospheric pressure to a volume of about 5 L, then the mixture was allowed to cool. The resulting solid was collected and washed with ethyl acetate (2×1.0 L) to provide the title compound.

Workup

  1. filtrationthe mixture was filtered through Celite (125 g) at 50° C.
  2. washrinsing with ethyl acetate (1.0 L)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted at 50° C. with additional ethyl acetate (7.5 L)
  5. washThe combined organic layers were washed with water (3×2.5 L)
  6. distillationdistilled
  7. customto remove about 2.5 L of solvent
  8. additionTetrahydrofuran (2.5 L) and silica bond thio silica gel (200 g) were added
  9. stirringThe mixture was stirred at 70° C. for 16 hr
  10. filtrationwas filtered
  11. washwashing the pad with ethyl acetate (1.0 L)
  12. concentrationThe combined filtrates were concentrated at atmospheric pressure to a volume of about 5 L
  13. temperatureto cool
  14. customThe resulting solid was collected
  15. washwashed with ethyl acetate (2×1.0 L)

Sources & evidence

ORD record
ord-05e8929f59434d45b41ca9f328a3614b
Source dataset
uspto-grants-2015_01
Patent number
US08927281B2

Reaction notes

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