Methanol → HCID 178499173, compound

HRID 1472158Notes

Reaction equation

HRID 1472158 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]([OH:13])=[O:12])=[N:9][NH:8][C:5]2=[N:6][CH:7]=1.OS(O)(=O)=O.[CH3:19]O>>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]([O:13][CH3:19])=[O:12])=[N:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 178524942HCID 178524942, compound

Product 1

HCID 178499173HCID 178499173, compound

Conditions

Temperature
70 °C

Procedure

To a solution of 5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid (XVIII) (1.6 Kg, 6.6 mol) in anhydrous MeOH (32 L) was added H2SO4 (160 mL) The reaction was slowly heated to 70° C. and stirred for 20 hours. The solution was concentrated under vacuum to a volume of 1.6 L. The residue was partitioned between DCM (120 L) and aqueous 10% NaHCO3 (32 L). The organic phase was separated and washed with aqueous 25% NaCl (32 L), dried over Na2SO4 and concentrated to a volume of 4.8 L. The product was crystallized by charging the solution with 3×n-heptane (8 L) while concentrating the volume to 4.8 L after each addition of n-heptane. The solid was filtered and dried under vacuum at 50° C. to produce methyl 5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carboxylate (XVII) (1.53 Kg, 6.0 mol, 80.6% purity, 90.4% assay yield). 1H NMR (DMSO-d6, 400 MHz) δ ppm 3.95 (s, 3H), 8.62 (d, J=2 Hz, 1H), 8.73 (d, J=2.4 Hz, 1H), 14.78 (brs, 1H); ESIMS found C8H6BrN3O2 m/z 256.0 (M+H).

Workup

  1. concentrationThe solution was concentrated under vacuum to a volume of 1.6 L
  2. customThe residue was partitioned between DCM (120 L) and aqueous 10% NaHCO3 (32 L)
  3. customThe organic phase was separated
  4. washwashed with aqueous 25% NaCl (32 L)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to a volume of 4.8 L
  7. customThe product was crystallized
  8. concentrationwhile concentrating the volume to 4.8 L
  9. additionafter each addition of n-heptane
  10. filtrationThe solid was filtered
  11. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-94aba898ffb74623a96c4507ba94652b
Source dataset
uspto-grants-2015_04
Patent number
US09012472B2

Reaction notes

Loading…