Potassium Carbonate → 4'-(Cyclopropylmethyl)-2-(methylsulfanyl)-4,5'-bipyrimidine

HRID 2359732Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2359732
[CH:1]1([CH2:4][C:5](=O)/[C:6](/[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([S:17][CH3:18])[N:12]=2)=[CH:7]\[N:8](C)[CH3:9])[CH2:3][CH2:2]1.C(O)(=O)C.C(N)=[NH:25].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH:1]1([CH2:4][C:5]2[C:6]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([S:17][CH3:18])[N:12]=3)=[CH:7][N:8]=[CH:9][N:25]=2)[CH2:3][CH2:2]1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 160693Formamidine acetateHCID 67983763(3Z)-1-Cyclopropyl-4-(dimethylamino)-3-[2-(methylsulfanyl)pyrimidin-4-yl]but-3-en-2-one

Produkt 1

HCID 679837614'-(Cyclopropylmethyl)-2-(methylsulfanyl)-4,5'-bipyrimidineAusbeute 33,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of (3Z)-1-cyclopropyl-4-(dimethylamino)-3-[2-(methylsulfanyl)pyrimidin-4-yl]but-3-en-2-one (3) (200 mg, 0.721 mmol), formamidine acetate (75 mg, 0.721 mmol), and K2CO3 (299 mg, 2.163 mmol) in DMF (6 mL) was stirred at 120° C. for 30 minutes, followed by stirring at rt for 18 hours. The reaction was partitioned between water and EtOAc. The organic layer was separated, and the aqueous layer was back-extracted. The organic extracts were combined, washed with brine, dried over sodium sulfate, then concentrated in vacuo. The crude product was purified by Biotage™ silica gel chromatography [10 g SNAP column, 30% EtOAc/heptane to 100% EtOAc] to obtain the desired product as a white solid (62.5 mg, 29.4% yield). The desired product contained a small amount of an unknown by-product and was carried on to the next step without further purification. MS (ES+): m/z=259.3 (100) [MH+2]. HPLC: tR=1.77 minutes over 3 minutes. Purity: 87.5% [HPLC (LC/MS) at 220 nm].

Aufarbeitung

  1. customThe reaction was partitioned between water and EtOAc
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was back-extracted
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by Biotage™ silica gel chromatography [10 g SNAP column, 30% EtOAc/heptane to 100% EtOAc]

Quellen und Nachweise

ORD-Eintrag
ord-99651511aa5840fab3c0a39bd48153b4
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08685993B2

Notizen zur Reaktion

Wird geladen…