Potassium Carbonate → (1-(5-(2-Fluorophenyl)pyrimidin-2-yl)-3-(methylthio)-1H-indol-6-yl)(morpholino)methanone

HRID 630442Notes

Reaction equation

HRID 630442 reaction equation
C(=O)([O-])[O-].[K+].[K+].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.Br[C:26]1[CH:27]=[N:28][C:29]([N:32]2[C:40]3[C:35](=[CH:36][CH:37]=[C:38]([C:41]([N:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)=[O:42])[CH:39]=3)[C:34]([S:49][CH3:50])=[CH:33]2)=[N:30][CH:31]=1.[F:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=1B(O)O>C1COCC1.O.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=1[C:26]1[CH:27]=[N:28][C:29]([N:32]2[C:40]3[C:35](=[CH:36][CH:37]=[C:38]([C:41]([N:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)=[O:42])[CH:39]=3)[C:34]([S:49][CH3:50])=[CH:33]2)=[N:30][CH:31]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 27343542-Fluorophenylboronic acidHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 118666053(1-(5-Bromopyrimidin-2-yl)-3-(methylthio)-1H-indol-6-yl)(morpholino)methanone

Product 1

HCID 118666168(1-(5-(2-Fluorophenyl)pyrimidin-2-yl)-3-(methylthio)-1H-indol-6-yl)(morpholino)methanone

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
30 °C

Procedure

Potassium carbonate (5.73 g, 41.57 mmol, 3.0 eq), Pd2(dba)3 (1.26 g, 1.39 mmol, 0.1 eq) and tri-tert-butyl phosphonium tetrafluoroborate (0.2 g, 0.69 mmol, 0.05 eq) were added at room temperature under an argon atmosphere to a stirred solution of (1-(5-bromopyrimidin-2-yl)-3-(methylthio)-1H-indol-6-yl)(morpholino)-methanone (6.0 g, 13.85 mmol, 1.0 eq) and (2-fluorophenyl)boronic acid (2.31 g, 16.62 mmol, 1.2 eq) in THF/water (100 mL, 4:1). The mixture was stirred for 2 h at 30° C., diluted with ethyl acetate (50 mL), and filtered through a pad of celite. The filtrate was washed with water, dried over sodium sulphate and evaporated. The residue was purified by column chromatography [100-200 mesh; ethyl acetate/petrolether=2:3]. Yield: 4.0 g (64% of theory).

Workup

  1. filtrationfiltered through a pad of celite
  2. washThe filtrate was washed with water
  3. dry with materialdried over sodium sulphate
  4. customevaporated
  5. customThe residue was purified by column chromatography [100-200 mesh; ethyl acetate/petrolether=2:3]

Sources & evidence

ORD record
ord-d65d15d98f71450ebf287597410efd5c
Source dataset
uspto-grants-2016_04
Patent number
US09315490B2

Reaction notes

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