Hydrochloric Acid → 4-(4-(2-(Methylthio)-6-oxo-1,6-dihydropyrimidin-5-yl)pyrimidin-2-ylamino)benzonitrile

HRID 1397176Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1397176
[C:1]([C:4]1[C:5](=[O:12])[NH:6][C:7]([S:10][CH3:11])=[N:8][CH:9]=1)(=O)[CH3:2].[C:13](OC(N(C)C)N(C)C)(C)(C)C.[C:25]([C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34]([NH2:36])=[NH:35])=[CH:29][CH:28]=1)#[N:26].C([O-])([O-])=O.[K+].[K+].Cl>>[CH3:11][S:10][C:7]1[NH:6][C:5](=[O:12])[C:4]([C:1]2[CH:2]=[CH:13][N:36]=[C:34]([NH:33][C:30]3[CH:29]=[CH:28][C:27]([C:25]#[N:26])=[CH:32][CH:31]=3)[N:35]=2)=[CH:9][N:8]=1

Komponenten

6

Edukt 5

HCID 313Hydrochloric Acid2×HCID 11430Potassium Carbonate2×HCID 79885tert-Butoxy bis(dimethylamino)methaneHCID 566989835-acetyl-2-(methylthio)pyrimidin-4(3H)-oneHCID 178510065HCID 178510065, Verbindung2×

Produkt 1

HCID 679833184-(4-(2-(Methylthio)-6-oxo-1,6-dihydropyrimidin-5-yl)pyrimidin-2-ylamino)benzonitrileAusbeute 47 %

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

5-Acetyl-2-(methylthio)pyrimidin-4(3H)-one (33) (1.094 g, 5.94 mmol) was dissolved in 1-tert-butoxy-N,N,N′,N′-tetramethylmethanediamine (12.26 mL, 59.4 mmol), then the reaction mixture was heated at 120° C. for 6 hours. The reaction mixture was concentrated in vacuo, and dried over high vacuum for 1 hour. The crude intermediate was taken up in DMF (31.6 mL), then 1-(4-cyanophenyl)guanidine (2.076 g, 8.91 mmol) and K2CO3 (4.10 g, 29.7 mmol) were added. The reaction mixture was heated at 120° C. for 48 hours. Additional 1-(4-cyanophenyl)guanidine (2.076 g, 8.91 mmol) and K2CO3 (3.69 g, 26.7 mmol) were added, and the reaction mixture was stirred at 120° C. for additional 18 hours. The reaction mixture was cooled to rt, then was slowly poured into an ice-cooled 1N HCl solution while stifling vigorously. The reaction mixture was neutralized with additional 1N HCl, then the reaction mixture was allowed to stir for an additional 30 minutes. The resulting precipitate was filtered, washed multiple times with DI water, 2-propanol, then diethyl ether. The resulting crude product was dried over high vacuum for 18 hours to obtain the desired product as a red/brown solid (940 mg, 47% yield). MS (ES+): m/z=337.2 (100) [MH+]. HPLC: tR=1.35 minutes over 3 minutes. Purity: 72% [HPLC (LC/MS) at 220 nm].

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customdried over high vacuum for 1 hour
  3. temperatureThe reaction mixture was heated at 120° C. for 48 hours
  4. temperatureThe reaction mixture was cooled to rt
  5. stirringto stir for an additional 30 minutes
  6. filtrationThe resulting precipitate was filtered
  7. washwashed multiple times with DI water, 2-propanol
  8. dry with materialThe resulting crude product was dried over high vacuum for 18 hours

Quellen und Nachweise

ORD-Eintrag
ord-b7da29fbbcaa4ba39e14bcae16278a96
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901147B2

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