Cesium carbonate → methyl 3-(6-(4-chlorophenyl)-1,5-dimethyl-2,4-dioxo-1,2-dihydrothieno[2,3-d]pyrimidin-3(4H)-yl)propanoate

HRID 63911Notes

Reaction equation

HRID 63911 reaction equation
Br[C:2]1[S:19][C:5]2[N:6]([CH3:18])[C:7](=[O:17])[N:8]([CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])[C:9](=[O:10])[C:4]=2[C:3]=1[CH3:20].[Cl:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1>[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([C:2]2[S:19][C:5]3[N:6]([CH3:18])[C:7](=[O:17])[N:8]([CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])[C:9](=[O:10])[C:4]=3[C:3]=2[CH3:20])=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 742994-Chlorophenylboronic acidHCID 118863153methyl 3-(6-bromo-1,5-dimethyl-2,4-dioxo-1,2-dihydrothieno[2,3-d]pyrimidin-3(4H)-yl)propanoate

Product 1

HCID 118863098methyl 3-(6-(4-chlorophenyl)-1,5-dimethyl-2,4-dioxo-1,2-dihydrothieno[2,3-d]pyrimidin-3(4H)-yl)propanoateYield 46.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 3-(6-bromo-1,5-dimethyl-2,4-dioxo-1,2-dihydrothieno[2,3-d]pyrimidin-3(4H)-yl)propanoate (180 mg, 0.498 mmol) in toluene (5 mL) was added 4-chlorophenylboronic acid (78 mg, 0.498 mmol) and aq. Cs2CO3 solution (1 M, 1 mL). The reaction was degassed under nitrogen gas (3×) then Pd(PPh3)4 (10 mg) was added. The reaction was heated at 100° C. for 18 h, cooled to RT then diluted with EA (10 mL). The organic layer was washed with brine (10 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with DCM/MeOH (80:1) to give methyl 3-(6-(4-chlorophenyl)-1,5-dimethyl-2,4-dioxo-1,2-dihydro thieno[2,3-d]pyrimidin-3(4H)-yl)propanoate (91 mg, 46.5% yield) as a yellow solid. LCMS: MH+ 393 and TR=1.956 min.

Workup

  1. customThe reaction was degassed under nitrogen gas (3×)
  2. additionPd(PPh3)4 (10 mg) was added
  3. temperaturecooled to RT
  4. additionthen diluted with EA (10 mL)
  5. washThe organic layer was washed with brine (10 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to a residue which
  8. customwas purified by chromatography
  9. washeluted with DCM/MeOH (80:1)

Sources & evidence

ORD record
ord-1761a465ee3a434c91f7199afb450b1e
Source dataset
uspto-grants-2016_09
Patent number
US09447114B2

Reaction notes

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