Potassium Carbonate → 1-methyl-2,4-dioxo-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoro methoxy)phenoxy)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde

HRID 63900

Reaktionsgleichung

Reaktionsgleichung von HRID 63900
Br[C:2]1[S:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[C:3]=1[CH:24]=[O:25].[F:26][C:27]([F:37])([F:36])[O:28][C:29]1[CH:30]=[C:31]([OH:35])[CH:32]=[CH:33][CH:34]=1.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.CC(=O)OCC.O>[CH3:22][N:6]1[C:5]2[S:23][C:2]([O:35][C:31]3[CH:32]=[CH:33][CH:34]=[C:29]([O:28][C:27]([F:26])([F:36])[F:37])[CH:30]=3)=[C:3]([CH:24]=[O:25])[C:4]=2[C:9](=[O:10])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)[C:7]1=[O:21]

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 27332613-(Trifluoromethoxy)phenolHCID 1188631326-bromo-1-methyl-2,4-dioxo-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde2×

Produkt 1

HCID 1188631081-methyl-2,4-dioxo-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoro methoxy)phenoxy)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehydeAusbeute 40,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of 6-bromo-1-methyl-2,4-dioxo-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-1,2, 3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde (See Compound 2, Step 4, 100 mg, 0.232 mmol) in DMSO (2 mL) was added 3-(trifluoromethoxy)phenol (82.6 mg, 0.464 mmol) and K2CO3 (96.1 mg, 0.696 mmol). The reaction was heated to 80° C. for 18 h, cooled to RT then diluted with EA (10 mL) and water (10 mL). The organic layer was washed with aq. 1N LiCl (3×5 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (5:1 to 3:1) to give 1-methyl-2,4-dioxo-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethoxy) phenoxy)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde (50 mg, 40.8% yield) as a solid. LCMS: [MH+-THP] 445 and TR=1.834 min.

Aufarbeitung

  1. temperaturecooled to RT
  2. washThe organic layer was washed with aq. 1N LiCl (3×5 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to a residue which
  5. customwas purified by chromatography
  6. washeluted with PE/EA (5:1 to 3:1)

Quellen und Nachweise

ORD-Eintrag
ord-597041cff2e44df5954ce7d2a5f75c6b
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09447114B2

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