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

HRID 472879ノート

反応式

HRID 472879 の反応式
[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]

参加物

4

反応物 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 178470701HCID 178470701、化合物

生成物 1

HCID 86670290Ethyl 2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetate収率 98.4%

反応条件

温度
120 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-b403f77f317648d8a3a5874bcfc8104e
出典データセット
uspto-grants-2014_01
特許番号
US08633200B2

反応ノート

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