Cesium carbonate → HCID 68183096, compound

HRID 1615579Notes

Reaction equation

HRID 1615579 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+].[C:31]1([C:37]#[CH:38])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>CN(C)C=O.CC#N.CC#N.Cl[Pd]Cl.O.CC(=O)OCC>[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]([C:38]#[C:37][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:10]2=3)=[CH:12][CH:13]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 10821PhenylacetyleneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 68183104HCID 68183104, compound

Product 1

HCID 68183096HCID 68183096, compoundYield 70.1%

Reagents, catalysts & solvents 4

HCID 6093782Bis(acetonitrile)dichloropalladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

In a 10-mL microwave vial, a suspension of 3-bromo-4-(4-chlorophenyl)-2-(morpholin-4-yl)-5,6-dihydrothieno[2,3-c]pyridin-7(4H)-one (69.5 mg, 0.162 mmol, single enantiomer of unknown configuration), cesium carbonate (0.146 g, 0.448 mmol) and phenylacetylene (0.107 mL, 0.975 mmol) in N,N-dimethylformamide (0.750 mL) was degassed by bubbling argon balloon for 5-10 min., then 2-dicyclohexylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (12.6 mg, 0.0265 mmol) and bis(acetonitrile)palladium(II) chloride (2.11 mg, 0.00812 mmol) was added. The vial was sealed, and the mixture was heated at 50° C. for 16 h. The r×n was cooled to rt, and combined with a previous r×n of same scale. The reaction was transferred to a separatory funnel with EA. Water was added, and the layers were separated. The aqueous layer was extracted w/EA. The organic layers were combined, washed w/brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude mixture was purified using column chromatography on silica gel (40 g ISCO column, gradient 100% hexanes to 100% EtOAc over 60 minutes to obtain impure product (51 mg). Final purification by HPLC gave the title product as an off-white solid (10 mg, 7%). LCMS: (FA) ES+ 449, 451. 1H NMR (400 MHz, DMSO) δ 7.47 (d, J=4.2 Hz, 1H), 7.40-7.32 (m, 5H), 7.27-7.23 (m, 2H), 7.21-7.17 (m, 2H), 4.31-4.29 (m, 1H), 3.91 (dd, J=12.9, 5.6 Hz, 1H), 3.79-3.76 (m, 4H), 3.57-3.52 (m, 2H), 3.49-3.44 (m, 2H), 3.30-3.27 (m, 1H).

Workup

  1. customwas degassed
  2. customby bubbling argon balloon for 5-10 min.
  3. customThe vial was sealed
  4. temperatureThe r×n was cooled to rt
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted w/EA
  7. washwashed w/brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude mixture was purified
  12. customover 60 minutes

Sources & evidence

ORD record
ord-934429de138e4b219d0bdf61c5c36eae
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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