Potassium Fluoride → HCID 23653618, compound

HRID 1514624Notes

Reaction equation

HRID 1514624 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:12](=[O:13])[C:11]3[CH:14]=[C:15]([CH2:18][S:19]([N:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])[CH:16]=[CH:17][C:10]=3[CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1.[CH3:25][N:26]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[N:27]1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[F-].[K+]>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].CN(C=O)C>[CH3:23][N:22]([CH3:24])[S:19]([CH2:18][C:15]1[CH:16]=[CH:17][C:10]2[CH:9]=[CH:8][C:5]3=[N:6][CH:7]=[C:2]([C:29]4[CH:28]=[N:27][N:26]([CH3:25])[CH:30]=4)[CH:3]=[C:4]3[C:12](=[O:13])[C:11]=2[CH:14]=1)(=[O:21])=[O:20]

Participants

7

Reactant 4

HCID 522689Potassium FluorideHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 57541251HCID 57541251, compound

Product 1

HCID 23653618HCID 23653618, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

1-(3-Chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N,N-dimethylmethanesulfonamide (1.44 g, 3.97 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H pyrazole (1.239 g, 5.95 mmol), tri-t-butylphosphonium tetrafluoroborate (0.104 g, 0.357 mmol), Pd2(dba)3 (0-145 g, 0.159 mmol), and potassium fluoride (0.761 g, 13.10 mmol) were combined as solids and then placed under a nitrogen atmosphere. DMF (39.7 ml) was added and the resulting suspension was heated to 130° C. and left to stir for 1 h. Then, the reaction was cooled to room temperature and partitioned between saturated aqueous sodium hydrogen carbonate (250 mL) and dichloromethane (250 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica (EtOAc+10% MeOH/Hexanes gradient) to afford the title compound as a yellow solid. 1H NMR (600 MHz, DMSO-D6) δ 9.21 (d, 1H); 8.54 (d, 1H); 8.47 (s, 1H); 8.19 (s, 1H); 8.14 (s, 1H); 7.81 (m, 2H); 7.40 (d, 1H); 7.32 (d, 1H); 4.63 (s, 2H); 3.88 (s, 3H); 2.74 (s, 6H). LRMS (APCI) calculated for C21H21N4O3S [M+H]+, 409.1. found 409.1.

Workup

  1. waitleft
  2. temperatureThen, the reaction was cooled to room temperature
  3. custompartitioned between saturated aqueous sodium hydrogen carbonate (250 mL) and dichloromethane (250 mL)
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on silica (EtOAc+10% MeOH/Hexanes gradient)

Sources & evidence

ORD record
ord-6156d4687de64c7a961ff2fc7cbdbc3c
Source dataset
uspto-grants-2012_07
Patent number
US08222269B2

Reaction notes

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