Nitrogen → 3-Bromo-5-(piperazin-1-yl)pyrazolo[1,5-a]pyrimidine

HRID 1844345Notes

Reaction equation

HRID 1844345 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8](Cl)=[N:7][C:6]=12.[NH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.N#N>C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)=[N:7][C:6]=12

Participants

5

Reactant 3

HCID 947NitrogenHCID 4837PiperazineHCID 454805073-Bromo-5-chloropyrazolo(1,5-a)pyrimidine

Product 1

HCID 866974343-Bromo-5-(piperazin-1-yl)pyrazolo[1,5-a]pyrimidineYield 86.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
120 °C

Procedure

3-Bromo-5-chloro-pyrazolo[1,5-a]pyrimidine (15.4 g, 66.2 mmol) and piperazine [110-85-0] (56.8 g, 659.5 mmol) were ground together in a mortar to an intimate mixture and transferred to a 250 mL round bottomed flask containing a magnetic stir bar. The flask was fitted to a reflux condenser, N2 blanketed, and the reaction pot immersed in an ambient temperature oil bath. While the neat solid mixture stirred, the bath was heated to 120° C. over 0.5 h and held at nominal temperature for a total of 2 h. The bath was removed and the molten reaction allowed to cool to approximately 75° C. Ethyl acetate was cautiously added down the condenser to dissolve the reaction product to prevent its setting up into a solid mass. The reaction solution was transferred to a separatory funnel, further diluted with ethyl acetate, and washed with water. The ethyl acetate extract was dried (MgSO4) and evaporated to obtain 16.1 g of clear yellow oil. The oil was crystallized from methanol to provide 15.8 g of light yellow crystalline powder in two crops, mp. 108-109° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.51 (s, 1 H) 3.16-3.24 (m, 3 H) 3.38 (s, 1 H) 3.93-4.00 (m, 3 H) 6.85 (d, J=7.83 Hz, 1 H) 8.03 (s, 1 H) 8.78 (d, J=8.08 Hz, 1 H) 9.61 (br. s., 1 H). 13C NMR (100 MHz, DMSO-d6) δ ppm 41.25, 42.16, 77.73, 97.78, 136.77, 144.01, 144.18, 155.53. LRMS (ESI) m/z 282.0/284.0 [(M+H)]+, calc'd for C10H12BrN5: 282.14.

Workup

  1. customtransferred to a 250 mL round bottomed flask
  2. additioncontaining a magnetic stir bar
  3. customThe flask was fitted to a reflux condenser
  4. customthe reaction
  5. custompot immersed in an ambient temperature
  6. customheld at nominal temperature for a total of 2 h
  7. customThe bath was removed
  8. customthe molten reaction
  9. temperatureto cool to approximately 75° C
  10. dissolutionto dissolve the reaction product
  11. customThe reaction solution was transferred to a separatory funnel
  12. washwashed with water
  13. extractionThe ethyl acetate extract
  14. dry with materialwas dried (MgSO4)
  15. customevaporated

Sources & evidence

ORD record
ord-13746bfa3cec45449d941c4c4a06d447
Source dataset
uspto-grants-2015_02
Patent number
US08946415B2

Reaction notes

Loading…