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

HRID 63913Notes

Reaction equation

HRID 63913 reaction equation
Br[CH2:2][C:3]1[C:11]2[C:10](=[O:12])[N:9]([CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])[C:8](=[O:19])[N:7]([CH3:20])[C:6]=2[S:5][C:4]=1[C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=1.[Cl:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1>[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:2][C:3]2[C:11]3[C:10](=[O:12])[N:9]([CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])[C:8](=[O:19])[N:7]([CH3:20])[C:6]=3[S:5][C:4]=2[C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 742994-Chlorophenylboronic acidHCID 118863122methyl 3-(5-(bromomethyl)-6-(4-chlorophenyl)-1-methyl-2,4-dioxo-1,2-dihydrothieno[2,3-d]pyrimidin-3(4H)-yl)propanoate

Product 1

HCID 118863103methyl 3-(5-(4-chlorobenzyl)-6-(4-chlorophenyl)-1-methyl-2,4-dioxo-1,2-dihydrothieno[2,3-d]pyrimidin-3(4H)-yl)propanoateYield 40.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 3-(5-(bromomethyl)-6-(4-chlorophenyl)-1-methyl-2,4-dioxo-1,2-dihydrothieno[2,3-d]pyrimidin-3(4H)-yl)propanoate (30 mg, 0.064 mmol) in toluene (2 mL) was added (4-chlorophenyl)boronic acid (9.94 mg, 0.064 mmol) and aq. Cs2CO3 solution (1 M, 0.5 mL). The reaction was degassed under nitrogen gas (3×) then Pd(PPh3)4 (3 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 (5 mL), dried over Na2SO4 and concentrated to a residue which was purified by Prep TLC eluted with PE/EA (1:1) to give methyl 3-(5-(4-chlorobenzyl)-6-(4-chlorophenyl)-1-methyl-2,4-dioxo-1,2-dihydrothieno[2,3-d]pyrimidin-3(4H)-yl)propanoate (13 mg, 40.6% yield) as a white solid. LCMS: MH+ 503 and TR=2.145 min.

Workup

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

Sources & evidence

ORD record
ord-6bf02fc2b10f49bfac57a286b20a3c16
Source dataset
uspto-grants-2016_09
Patent number
US09447114B2

Reaction notes

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