N,N-Dimethylaniline → Ethyl 7-chloro-6-(2-ethoxy-2-oxoethyl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate

HRID 921066Notes

Reaction equation

HRID 921066 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[CH2:5][C:6]1[C:7]([CH3:21])=[N:8][C:9]2[N:10]([N:13]=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:15]=2)[C:11]=1O)[CH3:2].CN(C)C1C=CC=CC=1.O=P(Cl)(Cl)[Cl:34]>>[Cl:34][C:11]1[N:10]2[N:13]=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:15]=[C:9]2[N:8]=[C:7]([CH3:21])[C:6]=1[CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:22]

Participants

4

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 178470702HCID 178470702, compound

Product 1

HCID 86691584Ethyl 7-chloro-6-(2-ethoxy-2-oxoethyl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylateYield 83%

Conditions

Temperature
120 °C

Procedure

A mixture of ethyl 6-(2-ethoxy-2-oxoethyl)-7-hydroxy-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (25 g, 81 mmol), and N,N-dimethylaniline (20.6 mL, 163 mmol) in POCl3 (100 mL) was heated at 120° C. for 3 h. Then the reaction was cooled to rt and concentrated in vacuo to half the volume. It was poured into a large quantity of ice water and stirred for 20 min. Precipitates formed and were collected by filtration. This solid was dissolved in ethyl acetate (1 L) and washed with water. The aqueous phase was back-extracted with ethyl acetate and the combined organic layers were washed with brine (200 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude was then triturated with EtOAc/hexane to afford ethyl 7-chloro-6-(2-ethoxy-2-oxoethyl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (22 g, 67.5 mmol, 83% yield) as light yellow solid. 1H NMR (500 MHz, CDCl3) δ 7.21 (s, 1H), 4.52 (q, J=7.2 Hz, 2H), 4.24 (q, J=7.2 Hz, 2H), 3.94 (s, 2H), 2.66 (s, 3H), 1.48 (t, J=7.0 Hz, 3H), 1.30 (t, J=7.2 Hz, 3H). LCMS (M+1)=326.2.

Workup

  1. temperatureThen the reaction was cooled to rt
  2. concentrationconcentrated in vacuo to half the volume
  3. additionIt was poured into a large quantity of ice water
  4. customPrecipitates
  5. customformed
  6. filtrationwere collected by filtration
  7. dissolutionThis solid was dissolved in ethyl acetate (1 L)
  8. washwashed with water
  9. extractionThe aqueous phase was back-extracted with ethyl acetate
  10. washthe combined organic layers were washed with brine (200 mL)
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe crude was then triturated with EtOAc/hexane

Sources & evidence

ORD record
ord-2f060cd3600d4197a1bb5ba5adbc9268
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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