Cesium carbonate → HCID 68183169, compound

HRID 1615576Notes

Reaction equation

HRID 1615576 reaction equation
Br[C:2]1[C:10]2[CH:9]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)[CH2:8][NH:7][C:6](=[O:18])[C:5]=2[S:4][C:3]=1[N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCO[CH2:33][CH2:32]1.C(OB(C=C)OCCCC)CCC>O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([CH:9]2[CH2:8][NH:7][C:6](=[O:18])[C:5]3[S:4][C:3]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[C:2]([CH:32]=[CH2:33])[C:10]2=3)=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 236543Dibutyl Vinylboronate (stabilized with Phenothiazine)HCID 68183104HCID 68183104, compound

Product 1

HCID 68183169HCID 68183169, compoundYield 61.1%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

In a 20 mL microwave vial a mixture of 3-bromo-4-(4-chlorophenyl)-2-(morpholin-4-yl)-5,6-dihydrothieno[2,3-c]pyridin-7(4H)-one (493.0 mg, 1.152 mmol, single enantiomer of unknown configuration), dicesium carbonate (1.13 g, 3.46 mmol), 1,4-dioxane (4.0 mL, 51 mmol), water (1.41 mL, 78.4 mmol) and vinylboronic acid dibutyl ester (381 uL, 1.73 mmol) was degassed by bubbling argon through the mixture for 10 min. Tetrakis(triphenylphosphine)-palladium(0) (66.6 mg, 0.0576 mmol) was added, the vial was sealed, and the r×n was heated at 100° C. for 15 h. The reaction was cooled to rt, diluted with water, and extracted with EA twice. The combined organics were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude material was (dry loaded on Celite and purified using column chromatography on silica gel (40 g ISCO column, gradient 100% hexanes to 100% EA over 60 minutes) to give the title compound (264 mg yellow solid, 61%). Final purification of 50 mg of this material by HPLC gave 30 mg pure product as a white solid. LCMS: (FA) ES+ 375, 377. 1H NMR (400 MHz, DMSO) δ 7.48 (d, J=4.6 Hz, 1H), 7.42-7.32 (m, 2H), 7.09-7.00 (m, 2H), 6.38 (dd, J=18.0, 11.8 Hz, 1H), 5.37 (dd, J=18.0, 1.7 Hz, 1H), 5.17 (dd, J=11.8, 1.6 Hz, 1H), 4.36 (d, J=4.3 Hz, 1H), 3.90 (dd, J=12.8, 5.0 Hz, 1H), 3.76-3.69 (m, 4H), 3.29 (dd, J=11.7, 5.1 Hz, 1H), 3.05-3.00 (m, 2H), 2.99-2.92 (m, 2H).

Workup

  1. customwas degassed
  2. customby bubbling argon through the mixture for 10 min
  3. customthe vial was sealed
  4. temperatureThe reaction was cooled to rt
  5. extractionextracted with EA twice
  6. washThe combined organics were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customdry
  11. custompurified
  12. customon silica gel (40 g ISCO column, gradient 100% hexanes to 100% EA over 60 minutes)

Sources & evidence

ORD record
ord-8729d9cb55584dca9dffffb0188a00a6
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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