N,N-Dimethylaniline → Ethyl 2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

HRID 472879Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 472879
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:24]([CH3:25])=[C:11]3[N:12]=[C:13]([CH3:23])[C:14]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:15](O)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.CN(C)C1C=CC=CC=1.O=P(Cl)(Cl)[Cl:37]>>[Cl:37][C:15]1[N:10]2[N:9]=[C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[C:24]([CH3:25])=[C:11]2[N:12]=[C:13]([CH3:23])[C:14]=1[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19]

Komponenten

4

Edukt 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 178470701HCID 178470701, Verbindung

Produkt 1

HCID 86670290Ethyl 2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetateAusbeute 98,4 %

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A suspension of ethyl 2-(2-(3-chlorophenyl)-7-hydroxy-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (11.5 g, 20.78 mmol), N,N-dimethylaniline (5.04 g, 41.6 mmol) and POCl3 (40 ml, 429 mmol) was heated (120° C. oil bath) for 3 hrs. The reaction was then concentrated in-vacuo and the dark residue taken up in EtOAc (75 mL) and stirred with ice-water (75 mL) for 30 min. The organic layer was washed with water (2×50 mL). The combined aqueous layers were extracted with EtOAc (50 mL) and the combined organic layers washed with brine (50 mL), dried (Na2SO4), filtered and concentrated to give a brown solid. The crude product was purified by silica gel flash column chromatography, eluting with 10%-30% EtOAc in hexane. Product fractions were pooled and concentrated under reduced pressure, affording the purified product, ethyl 2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (8.3 g, 20.45 mmol, 98% yield) as an off-white powdery solid. 1H NMR (500 MHz, CDCl3) δ: 7.87 (t, J=1.7 Hz, 1H), 7.74 (dt, J=7.3, 1.5 Hz, 1H), 7.44-7.36 (m, 2H), 4.21 (q, J=7.1 Hz, 2H), 3.89 (s, 2H), 2.62 (s, 3H), 2.52 (s, 3H), 1.28 (t, J=7.2 Hz, 3H).

Aufarbeitung

  1. concentrationThe reaction was then concentrated in-vacuo
  2. washThe organic layer was washed with water (2×50 mL)
  3. extractionThe combined aqueous layers were extracted with EtOAc (50 mL)
  4. washthe combined organic layers washed with brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a brown solid
  9. customThe crude product was purified by silica gel flash column chromatography
  10. washeluting with 10%-30% EtOAc in hexane
  11. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-b403f77f317648d8a3a5874bcfc8104e
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08633200B2

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