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

HRID 1630304Notes

Reaction equation

HRID 1630304 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 (20.62 mL, 163 mmol) in POCl3 (100 mL) was heated at 120° C. for 3 h. Then, cooled, concentrated to half the volume and then poured into ice water and stirred for 20 min. Precipitates formed were filtered and solids were dissolved in ethyl acetate (1 L) and washed with water. Filterate was then extracted with ethyl acetate and combined organic layers were washed with brine (200 mL), dried (Na2SO4), filtered and concentrated. 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+H)=326.2.

Workup

  1. temperatureThen, cooled
  2. concentrationconcentrated to half the volume
  3. additionpoured into ice water
  4. customPrecipitates
  5. customformed
  6. filtrationwere filtered
  7. dissolutionsolids were dissolved in ethyl acetate (1 L)
  8. washwashed with water
  9. extractionFilterate was then extracted with ethyl acetate
  10. washwere washed with brine (200 mL)
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude was then triturated with EtOAc/hexane

Sources & evidence

ORD record
ord-0d4271d0e4e94b46a6313dd3a2ef5383
Source dataset
uspto-grants-2014_07
Patent number
US08791108B2

Reaction notes

Loading…