Sodium Hydroxide → HCID 178434433, compound

HRID 1472156Notes

Reaction equation

HRID 1472156 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[NH:4][N:3]=1.CC([O-])=O.[Na+].[Br:16]Br.[OH-].[Na+]>CC(O)=O.C(Cl)Cl.O>[Br:16][C:8]1[CH:9]=[C:10]2[C:2]([CH3:1])=[N:3][NH:4][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 24408BromineHCID 517045Sodium AcetateHCID 178434440HCID 178434440, compound

Product 1

HCID 178434433HCID 178434433, compoundYield 48.4%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-methyl-1H-pyrazolo[3,4-b]pyridine (XIV) (12.7 Kg, 95.4 mol) in HOAc (57 L) was added NaOAc (20.4 Kg, 248 mol), water (13.3 L), and Br2 (40 L, 780 mol). The reaction was stirred at room temperature for 5 hours and then at 115° C. for 6 hours. The reaction was cooled to room temperature and diluted with DCM (686 L). To this solution was added water (508 L) and cooled to 0° C. followed by dropwise addition of aqueous 30% NaOH while maintaining the temperature <20° C. under pH=9. The mixture was filtered through diatomaceous earth (14 Kg) followed by washing the diatomaceous earth with 3×DCM (50 L). The organic layer was separated, washed with aqueous 25% NaCl (200 L) and concentrated under vacuum to a volume of 70 L. The product was crystallized by charging the solution with 3×n-heptane (88 L) while concentrating the volume to 70 L after each addition of n-heptane. The solid was filtered and washed 3×n-heptane (22 L). The solid was dried under vacuum at 45° C. to yield 5-bromo-3-methyl-1H-pyrazolo[3,4-b]pyridine (XXI) (9.8 Kg, 46.2 mol, 92.6% purity, 48.4% assay yield). 1H NMR (DMSO-d6, 400 MHz) δ ppm 2.48 (s, 3H), 8.50-8.55 (m, 2H), 13.42 (brs, 1H); ESIMS found C7H6BrN3 m/z 213.7 (M+H).

Workup

  1. waitat 115° C. for 6 hours
  2. temperatureThe reaction was cooled to room temperature
  3. temperaturecooled to 0° C.
  4. temperaturewhile maintaining the temperature <20° C. under pH=9
  5. filtrationThe mixture was filtered through diatomaceous earth (14 Kg)
  6. washby washing the diatomaceous earth with 3×DCM (50 L)
  7. customThe organic layer was separated
  8. washwashed with aqueous 25% NaCl (200 L)
  9. concentrationconcentrated under vacuum to a volume of 70 L
  10. customThe product was crystallized
  11. concentrationwhile concentrating the volume to 70 L
  12. additionafter each addition of n-heptane
  13. filtrationThe solid was filtered
  14. washwashed 3×n-heptane (22 L)
  15. customThe solid was dried under vacuum at 45° C.

Sources & evidence

ORD record
ord-b0dadde4a7c048c4ae5a5fb65e165516
Source dataset
uspto-grants-2015_04
Patent number
US09012472B2

Reaction notes

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