Potassium Carbonate → (1-(5-(1-Methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)-3-(methylthio)-1H-indol-6-yl)(morpholino)methanone

HRID 630484Notes

Reaction equation

HRID 630484 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.[CH3:51][N:52]1[CH:56]=[C:55](B(O)O)[CH:54]=[N:53]1>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]>[CH3:51][N:52]1[CH:56]=[C:55]([C:26]2[CH:27]=[N:28][C:29]([N:32]3[C:40]4[C:35](=[CH:36][CH:37]=[C:38]([C:41]([N:43]5[CH2:48][CH2:47][O:46][CH2:45][CH2:44]5)=[O:42])[CH:39]=4)[C:34]([S:49][CH3:50])=[CH:33]3)=[N:30][CH:31]=2)[CH:54]=[N:53]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 112635011-Methyl-1H-pyrazole-4-boronic acidHCID 118666053(1-(5-Bromopyrimidin-2-yl)-3-(methylthio)-1H-indol-6-yl)(morpholino)methanone

Product 1

HCID 118676819(1-(5-(1-Methyl-1H-pyrazol-4-yl)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 (254 mg, 1.846 mmol, 2.0 eq), Pd2(dba)3 (84 mg, 0.0923 mmol, 0.1 eq) and tri-tert-butylphosphonium tetrafluoroborate (13 mg, 0.046 mmol, 0.05 eq) were added to a solution of (1-(5-bromopyrimidin-2-yl)-3-(methylthio)-1H-indol-6-yl)(morpholino)methanone (400 mg, 0.923 mmol, 1.0 eq) and (1-methyl-1H-pyrazol-4-yl)boronic acid (140 mg, 1.108 mmol, 1.2 eq) in THF/water (20 mL, 4:1) stirred under an argon atmosphere at 30° C. The reaction mixture was stirred at the same temperature for 2 h and the cooled to ambient temperature and diluted with ethyl acetate (10 mL). The mixture was filtered through a pad of celite, washed with water, dried over sodium sulfate and evaporated. The residue was purified by column chromatography [100-200 mesh, 2% methanol in dichloromethane]. White solid. Yield: 380 mg (95% of theory)

Workup

  1. stirringThe reaction mixture was stirred at the same temperature for 2 h
  2. temperaturethe cooled to ambient temperature
  3. filtrationThe mixture was filtered through a pad of celite
  4. washwashed with water
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe residue was purified by column chromatography [100-200 mesh, 2% methanol in dichloromethane]

Sources & evidence

ORD record
ord-0e3424909e1f4df08fb0053a5ea42797
Source dataset
uspto-grants-2016_04
Patent number
US09315490B2

Reaction notes

Loading…