Cesium carbonate → HCID 56971356, compound

HRID 1615522Notes

Reaction equation

HRID 1615522 reaction equation
Br[C:2]1[S:19][C:5]2[C:6](=[O:18])[N:7]([CH3:17])[CH2:8][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:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=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[CH2:8][N:7]([CH3:17])[C:6](=[O:18])[C:5]3[S:19][C:2]([C:23]4[CH:24]=[CH:25][N:20]=[CH:21][CH:22]=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 68183342HCID 68183342, compound

Product 1

HCID 56971356HCID 56971356, compoundYield 20.1%

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

2-bromo-4-(4-chlorophenyl)-6-methyl-5,6-dihydrothieno[2,3-c]pyridin-7(4H)-one (0.0400 g, 0.112 mmol) and pyridine-4-boronic acid (0.02575 g, 0.2095 mmol) were dissolved in a mixture of 1,4-dioxane (2 mL) and water (0.2 mL). Cesium carbonate (0.1096 g, 0.3364 mmol) was added followed by [1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloride (0.0111 g, 0.0134 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 (10.00 mL) and extracted with EtOAc (10.00 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified using preparative HPLC to afford the product (0.0080 g, 19.0%) as a white solid. LC/MS (AA) ES+ 355, 357, 358, 359. 1H NMR (DMSO, 400 MHz): δ 8.59-8.58 (2H, m), 7.69-7.67 (2H, m), 7.51 (1H, s), 7.44-7.42 (2H, m), 7.31-7.29 (2H, m), 5.00 (1H, J=6.40, Hz, t), 3.95-3.91 (1H, m), 3.71-3.66 (1H, m), 2.50 (3H, s).

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. customquenched by the addition of a saturated aqueous solution of sodium bicarbonate (10.00 mL)
  3. extractionextracted with EtOAc (10.00 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 was purified

Sources & evidence

ORD record
ord-72cb0cb5803640f781ed102c749f4079
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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