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

HRID 63916Notes

Reaction equation

HRID 63916 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:25][C:11]3[N:12]([CH3:24])[C:13](=[O:23])[N:14]([CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20])[C:15](=[O:16])[C:10]=3[C:9]=2[CH3:26])=[CH:4][CH:3]=1.[F:27][C:28]([F:40])([F:39])[O:29]C1C=C(B(O)O)C=CC=1.[C:41]([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1>[CH3:24][N:12]1[C:11]2[S:25][C:8]([C:5]3[CH:6]=[CH:7][CH:2]=[C:3]([O:29][C:28]([F:40])([F:39])[F:27])[CH:4]=3)=[C:9]([CH3:26])[C:10]=2[C:15](=[O:16])[N:14]([CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:41])=[O:20])[C:13]1=[O:23]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 118863098methyl 3-(6-(4-chlorophenyl)-1,5-dimethyl-2,4-dioxo-1,2-dihydrothieno[2,3-d]pyrimidin-3(4H)-yl)propanoate2×

Product 1

HCID 118863112ethyl 3-(1,5-dimethyl-2,4-dioxo-6-(3-(trifluoromethoxy)phenyl)-1,2-dihydrothieno[2,3-d]pyrimidin-3 (4H)-yl)propanoateYield 63.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of ethyl 3-(6-bromo-1,5-dimethyl-2,4-dioxo-1,2-dihydrothieno[2,3-d]pyrimidin-3(4H)-yl)propanoate (See Compound 24, Step 4, 150 mg, 0.415 mmol) in toluene (3 mL) was added (3-(trifluoro methoxy)phenyl)boronic acid (102 mg, 0.498 mmol) and aq. Cs2CO3 solution (1 M, 0.5 mL). The reaction was degassed under nitrogen gas (3×) then Pd(PPh3)4 (24 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 PE/EA (4:1) to give ethyl 3-(1,5-dimethyl-2,4-dioxo-6-(3-(trifluoromethoxy)phenyl)-1,2-dihydrothieno[2,3-d]pyrimidin-3 (4H)-yl)propanoate (120 mg, 63.8% yield) as a yellow solid. LCMS: MH+ 457 and TR=2.045 min.

Workup

  1. customThe reaction was degassed under nitrogen gas (3×)
  2. additionPd(PPh3)4 (24 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 PE/EA (4:1)

Sources & evidence

ORD record
ord-14d1c59bf8db43b58fae3d719e889e8f
Source dataset
uspto-grants-2016_09
Patent number
US09447114B2

Reaction notes

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