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

HRID 472879Notes

Reaction equation

HRID 472879 reaction equation
[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]

Participants

4

Reactant 3

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

Product 1

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

Conditions

Temperature
120 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-b403f77f317648d8a3a5874bcfc8104e
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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