Benzeneethanamine, alpha-methyl-, phosphate (1:1) → 6-(2-Fluoropyridin-3-yl)-2-methylpyrimidin-4-amine

HRID 1622017

Reaktionsgleichung

Reaktionsgleichung von HRID 1622017
[NH2:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[C:4]([CH3:9])[N:3]=1.[F:10][C:11]1[C:16](B(O)O)=[CH:15][CH:14]=[CH:13][N:12]=1.CC(N)CC1C=CC=CC=1.OP(O)(O)=O.C([O-])(=O)C.[K+]>O.CCO>[F:10][C:11]1[C:16]([C:6]2[N:5]=[C:4]([CH3:9])[N:3]=[C:2]([NH2:1])[CH:7]=2)=[CH:15][CH:14]=[CH:13][N:12]=1

Komponenten

7

Edukt 4

HCID 62885Benzeneethanamine, alpha-methyl-, phosphate (1:1)HCID 2867546-Chloro-2-methylpyrimidin-4-amineHCID 517044Potassium AcetateHCID 27832702-Fluoropyridine-3-boronic acid

Produkt 1

HCID 665999906-(2-Fluoropyridin-3-yl)-2-methylpyrimidin-4-amineAusbeute 84,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a 20 mL microwave vials was added 4-Amino-6-chloro-2-methylpyrimidine (SynChem) (0.500 g, 3.48 mmol), 2-fluoro-3-pyridineboronic acid (Aldrich) (0.687 g, 4.88 mmol), Amphos (Aldrich) (0.123 g, 0.174 mmol), potassium acetate (Aldrich) (0.653 mL, 10.45 mmol), EtOH (12 mL), and water (1.2 mL). The vial was degassed by bubbling N2 for 5 min then sealed off and microwave heated at 100° C. for 20 min. The reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (80 g, 20% to 40% acetone in hexanes) to afford the desired product as a yellow solid (600 mg). MS (ESI pos. ion) m/z: 205.1. 1H NMR (300 MHz, CDCl3) δ ppm 2.59 (s, 3H) 4.96 (br. s., 2H) 6.89 (s, 1H) 7.34 (ddd, J=7.34, 4.93, 1.90 Hz, 1H) 8.27 (dd, J=3.00, 1.53 Hz, 1H) 8.66 (ddd, J=9.76, 7.64, 2.05 Hz, 1H).

Aufarbeitung

  1. customThe vial was degassed
  2. customby bubbling N2 for 5 min
  3. customthen sealed off
  4. customThe reaction mixture was partitioned between EtOAc and water
  5. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography (80 g, 20% to 40% acetone in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-6514806d4af54291b8b02ecae42b4d5b
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772480B2

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