Sodium Hydroxide → 3-Bromo-5-chloropyrazolo(1,5-a)pyrimidine

HRID 1478255Notes

Reaction equation

HRID 1478255 reaction equation
C([O-])(=O)C.[Na+].[Cl:6][C:7]1[CH:12]=[CH:11][N:10]2[N:13]=[CH:14][CH:15]=[C:9]2[N:8]=1.[Br:16]Br.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+].[OH-].[Na+]>C(O)(=O)C>[Br:16][C:15]1[CH:14]=[N:13][N:10]2[CH:11]=[CH:12][C:7]([Cl:6])=[N:8][C:9]=12

Participants

7

Reactant 5

HCID 14798Sodium HydroxideHCID 24408Bromine2×HCID 517045Sodium AcetateHCID 656671Sodium PyrosulfiteHCID 210717595-Chloropyrazolo(1,5-a)pyrimidine

Product 1

HCID 454805073-Bromo-5-chloropyrazolo(1,5-a)pyrimidineYield 87.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

Sodium acetate [127-09-3] (24.1 g, 293.9 mmol) was added to a solution of 5-chloro-pyrazolo[1,5-a]pyrimidine [29274-24-6], (30.1 g, 195.7 mmol) in glacial acetic acid (395 mL) and allowed to stir at ambient temperature until all of the solid had dissolved. An ice bath was then put in place, and the solution chilled to 0° C. Bromine [7726-95-6] (11.0 mL, 214.7 mmol) was added drop by drop into the 0° C. buffered acetic acid reaction solution over 35 minutes which gradually became a thick stirred suspension. Upon completion of the bromine addition, the suspension was allowed to stir for a further 15 minutes then was slowly poured into an aqueous (5% w/v) solution (1 L) of sodium metabisulfite [7681-57-4] stirred in an ice bath. Solid sodium hydroxide [1310-73-2] pellets were added to the stirred suspension, at a rate to maintain an internal temperature of less than 40° C., until pH of the supernatant was determined to be approximately 8 by pH paper. Precipitated product was isolated by filtration, the filter cake washed with water, and allowed to dry to afford 39.8 g of light yellow powder, mp. 173-174° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.22 (d, J=7.33 Hz, 1H) 8.44 (s, 1 H) 9.21 (d, J=7.07 Hz, 1 H). 13C NMR (100 MHz, DMSO-d6) δ ppm 82.84, 109.99, 138.94, 143.76, 145.61, 151.18. LRMS (ESI) m/z 231.8/233.8/235.8 [(M+H)]+, calc'd for C6H3BrClN3: 232.47.

Workup

  1. dissolutionhad dissolved
  2. customAn ice bath was then put in place
  3. temperaturethe solution chilled to 0° C
  4. stirringto stir for a further 15 minutes
  5. stirringstirred in an ice bath
  6. temperatureto maintain an internal temperature of less than 40° C.
  7. customPrecipitated product was isolated by filtration
  8. washthe filter cake washed with water
  9. customto dry

Sources & evidence

ORD record
ord-beecb8b844bd4a699c5843af7c9647ec
Source dataset
uspto-grants-2016_08
Patent number
US09403832B2

Reaction notes

Loading…