Sodium hydride → 5-[1-(3-Methoxy-propyl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

HRID 1505700Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1505700
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]([C:13]3[N:18]=[CH:17][C:16]([C:19]4[CH:20]=[N:21][NH:22][CH:23]=4)=[CH:15][N:14]=3)[CH:10]=[CH:11][CH:12]=2)[CH:4]=[N:3]1.[H-].[Na+].Cl[CH2:27][CH2:28][CH2:29][O:30][CH3:31]>CN(C=O)C>[CH3:31][O:30][CH2:29][CH2:28][CH2:27][N:21]1[CH:20]=[C:19]([C:16]2[CH:17]=[N:18][C:13]([C:9]3[CH:10]=[CH:11][CH:12]=[C:7]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)[CH:8]=3)=[N:14][CH:15]=2)[CH:23]=[N:22]1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 1189271-Chloro-3-methoxypropaneHCID 729446552-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-(1H-pyrazol-4-yl)pyrimidine

Produkt 1

HCID 729442235-[1-(3-Methoxy-propyl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel3×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of 2-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-(1H-pyrazol-4-yl)pyrimidine (example 3, 130 mg; 0.43 mmol; 1.0 eq.) in dry DMF (1 mL) was added over a suspension of NaH (60% in oil, 21 mg; 0.86 mmol; 2.0 eq.) in dry DMF (1 mL) maintained at 0° C. under nitrogen atmosphere. The resulting mixture was stirred for one hour at 0° C. then heated at 100° C. O/N after the addition of a solution of 1-chloro-3-methoxypropane (47 mg; 0.43 mmol; 1.0 eq.) in DMF (2 mL). Reaction mixture was then cooled down to RT, quenched with water and extracted with EtOAc (three times). Combined organic phases were washed with water, brine, dried over magnesium sulfate, filtered and concentrated. The resulting solid was dried O/N at 60° C. under reduced pressure to give the title compound a beige powder (165 mg; 75%). 1H NMR (300 MHz, DMSO-d6) δ 9.16 (s, 2H), 8.58-8.49 (m, 1H), 8.46 (s, 1H), 8.30-8.17 (m, 2H), 8.17-8.11 (m, 1H), 7.96-7.89 (m, 1H), 7.75-7.68 (m, 1H), 7.51 (t, J=7.8 Hz, 1H), 4.22 (t, J=7.0 Hz, 2H), 3.90 (s, 3H), 3.39-3.30 (m, 2H), 3.25 (s, 3H), 2.15-1.97 (m, 2H). HPLC (Condition A): Rt 3.34 min (purity 97.1%). MS (ESI+): 375.5.

Aufarbeitung

  1. temperaturethen heated at 100° C
  2. customReaction mixture
  3. temperaturewas then cooled down to RT
  4. customquenched with water
  5. extractionextracted with EtOAc (three times)
  6. washCombined organic phases were washed with water, brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting solid was dried O/N at 60° C. under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-55f9c2401fef4908a4809f7fa2a96d7e
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09216991B2

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