Dimethylformamide → 4'-(Cyclopropylmethyl)-N-methyl-2-(methylthio)-[4,5'-bipyrimidin]-2'-amine

HRID 1397137Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1397137
[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]([CH3:10])C)[CH2:3][CH2:2]1.[CH3:20][NH:21]C(N)=N.C([O-])([O-])=O.[K+].[K+].C[N:32](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]=[C:10]([NH:21][CH3:20])[N:32]=2)[CH2:2][CH2:3]1

Komponenten

5

Edukt 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 67983763(3Z)-1-Cyclopropyl-4-(dimethylamino)-3-[2-(methylsulfanyl)pyrimidin-4-yl]but-3-en-2-oneHCID 178485088HCID 178485088, Verbindung

Produkt 1

HCID 679838984'-(Cyclopropylmethyl)-N-methyl-2-(methylthio)-[4,5'-bipyrimidin]-2'-amineAusbeute 86 %

Versuchsvorschrift

A solution of (3Z)-1-cyclopropyl-4-(dimethylamino)-3-[2-(methylsulfanyl)pyrimidin-4-yl]but-3-en-2-one (3) (810 mg, 2.92 mmol), N-methylguanidine (480 mg, 4.38 mmol), and K2CO3 (1211 mg, 8.76 mmol) in DMF (28 mL) was stirred at 120° C. for 2 hours, followed by stifling 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 [100 g SNAP column, 30% EtOAc/heptane to 100% EtOAc] to afford the desired product as a white solid (720 g, 86% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.12 (br. s., 2 H) 0.37 (d, J=7.07 Hz, 2 H) 1.07 (br. s., 1 H) 2.81 (d, J=6.57 Hz, 2H) 2.87 (d, J=5.05 Hz, 3 H) 7.39 (d, J=5.05 Hz, 1 H) 7.49 (br. s., 1 H) 8.49 (br. s., 1 H) 8.60 (d, J=5.05 Hz, 1 H). MS (ES+): m/z=288.2/289.2/290.2 (100/20/10) [MH+]. HPLC: tR=1.28 minutes over 3 minutes. Purity: 100% [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 [100 g SNAP column, 30% EtOAc/heptane to 100% EtOAc]

Quellen und Nachweise

ORD-Eintrag
ord-fc5dbceeeb5f421b8864ff2992617a5e
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901147B2

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