Potassium Carbonate → 4'-(Cyclopropylmethyl)-2'-(methylsulfanyl)-N-pyridin-4-yl-4,5'-bipyrimidin-2-amine

HRID 2359755Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2359755
[CH:1]1([CH2:4][C:5](=O)/[C:6](/[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)[N:12]=2)=[CH:7]\N(C)C)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].S(O)(O)(=O)=O.[CH3:36][S:37][C:38](=[NH:40])[NH2:39]>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]([NH:17][C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[N:12]=3)=[CH:7][N:39]=[C:38]([S:37][CH3:36])[N:40]=2)[CH2:3][CH2:2]1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 752702-Methyl-2-thiopseudourea sulfateHCID 67983720(3Z)-1-Cyclopropyl-4-(dimethylamino)-3-[2-(pyridin-4-ylamino)pyrimidin-4-yl]but-3-en-2-one

Produkt 1

HCID 679838584'-(Cyclopropylmethyl)-2'-(methylsulfanyl)-N-pyridin-4-yl-4,5'-bipyrimidin-2-amineAusbeute 3,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a solution of (Z)-1-cyclopropyl-4-(dimethylamino)-3-(2-(pyridin-4-ylamino)pyrimidin-4-yl)but-3-en-2-one (9) (200 mg, 0.618 mmol) in DMF (5.154 ml) was added potassium carbonate (256 mg, 1.855 mmol) and 2-methyl-2-thiopseudourea sulfate (129 mg, 0.928 mmol). The reaction was warmed to 120° C. and stirred for 1 hr. The solvent was evaporated and the crude residue partitioned between DCM and water. The organic layer was washed with brine, dried with sodium sulfate, and concentrated. The crude product was purified by flash chromatography with a gradient of 2-10% MeOH in DCM and further purified reverse phase HPLC with a gradient of 10-100% MeCN in H2O to give 7.8 mg of the desired product as a white solid. HRMS (ES+)=351.1391. UV-LC: 100/100% UV purity at 214/254 nm; HPLC: tR=3.38 minute over 7.75 minutes. 1H NMR (400 MHz, MeOD) δ ppm 0.10-0.14 (m, 2H) 0.41-0.47 (m, 2H) 1.03-1.15 (m, 1H) 2.63 (s, 3H) 2.94 (d, J=7.07 Hz, 2H) 7.18 (d, J=5.56 Hz, 1H) 7.83 (d, J=7.07 Hz, 2H) 8.31 (d, J=7.07 Hz, 2H) 8.64 (s, 1H) 8.65 (d, J=5.05 Hz, 1H)

Aufarbeitung

  1. customThe solvent was evaporated
  2. customthe crude residue partitioned between DCM and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography with a gradient of 2-10% MeOH in DCM and further purified reverse phase HPLC with a gradient of 10-100% MeCN in H2O

Quellen und Nachweise

ORD-Eintrag
ord-88e16acb87b54197b3946ff7bea224e2
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08685993B2

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