Potassium Phosphate, Tribasic → 5-(1-hydroxy-3-methylbutyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy) propyl)-6-(3-(trifluoromethoxy)phenyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 63905

Reaktionsgleichung

Reaktionsgleichung von HRID 63905
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]([OH:29])[CH2:25][CH:26]([CH3:28])[CH3:27].[F:30][C:31]([F:43])([F:42])[O:32][C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:29][CH:24]([C:3]1[C:4]2[C:9](=[O:10])[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:7](=[O:21])[N:6]([CH3:22])[C:5]=2[S:23][C:2]=1[C:35]1[CH:36]=[CH:37][CH:38]=[C:33]([O:32][C:31]([F:30])([F:42])[F:43])[CH:34]=1)[CH2:25][CH:26]([CH3:28])[CH3:27]

Komponenten

6

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 1188630916-bromo-5-(1-hydroxy-3-methylbutyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Produkt 1

HCID 1188631145-(1-hydroxy-3-methylbutyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy) propyl)-6-(3-(trifluoromethoxy)phenyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dioneAusbeute 61,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a solution of 6-bromo-5-(1-hydroxy-3-methylbutyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (70 mg, 0.143 mmol) in dioxane (2 mL) was added (3-(trifluoromethoxy)phenyl)boronic acid (58.9 mg, 0.286 mmol), Pd(PPh3)4 (10 mg) and aq. 2M K3PO4 (0.4 mL). The reaction was heated at 85° C. for 2 h then cooled to RT and filtered. The filtrate was diluted with DCM (10 mL) and water (10 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (10:1 to 5:1) to give 5-(1-hydroxy-3-methylbutyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethoxy)phenyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (50 mg, 61.2% yield) as a solid. LCMS: [MH+-THP] 487 and TR=2.079 min.

Aufarbeitung

  1. temperaturethen cooled to RT
  2. filtrationfiltered
  3. additionThe filtrate was diluted with DCM (10 mL) and water (10 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated to a residue which
  6. customwas purified by chromatography
  7. washeluted with PE/EA (10:1 to 5:1)

Quellen und Nachweise

ORD-Eintrag
ord-22b2e4e664e44b948cee633581b8b3ba
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09447114B2

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