Cesium carbonate → HCID 68183266, compound

HRID 1615536Notes

Reaction equation

HRID 1615536 reaction equation
Br[C:2]1[S:20][C:5]2[C:6](=[O:19])[NH:7][C:8]([CH3:18])([CH3:17])[CH:9]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=3)[C:4]=2[CH:3]=1.[N:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([CH:9]2[C:8]([CH3:18])([CH3:17])[NH:7][C:6](=[O:19])[C:5]3[S:20][C:2]([C:24]4[CH:25]=[CH:26][N:21]=[CH:22][CH:23]=4)=[CH:3][C:4]2=3)=[CH:11][CH:12]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 68183139HCID 68183139, compound

Product 1

HCID 68183266HCID 68183266, compoundYield 13.7%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a 20 mL vial was added a solution of 2-bromo-4-(4-chlorophenyl)-5,5-dimethyl-5,6-dihydrothieno[2,3-c]pyridin-7(4H)-one (0.0440 g, 0.119 mmol) and pyridine-4-boronic acid (0.02726 g, 0.2218 mmol) in 1,4-dioxane (3.0 mL) and water (0.300 mL). Cesium carbonate (0.1160 g, 0.3561 mmol) was added followed by [1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloride (0.0117 g, 0.0142 mmol). The reaction mixture was heated to 90° C. and allowed to stir for 18 h. The reaction was cooled to ambient temperature and quenched by the addition of a saturated aqueous solution of sodium bicarbonate (10 mL) and extracted with EtOAc (10 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material as purified by prep HPLC to afford the product (0.0060 g, 13%) as a yellow solid. LC/MS (AA) ES+ 369, 371, 373. 1H NMR (dmso-d6, 400 MHz): d 8.59-8.57 (2H, m), 7.91 (1H, s), 7.68-7.66 (2H, m), 7.60 (1H, s), 7.40-7.38 (2H, m), 7.19-7.17 (2H, m), 4.21 (1H, s), 1.36 (3H, s), 0.94 (3H, s).

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. customquenched by the addition of a saturated aqueous solution of sodium bicarbonate (10 mL)
  3. extractionextracted with EtOAc (10 mL×3)
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material as purified by prep HPLC

Sources & evidence

ORD record
ord-eb80030f79ae4043afc884143033a3c9
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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