Iodoethane → 6-cyclopropyl-1-ethyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid

HRID 476050Notes

Reaction equation

HRID 476050 reaction equation
[CH:1]1([C:4]2[CH:5]=[C:6]([C:13]([O:15]CC)=[O:14])[C:7]3[CH:12]=[N:11][NH:10][C:8]=3[N:9]=2)[CH2:3][CH2:2]1.[H-].[Na+].I[CH2:21][CH3:22].[OH-].[Na+]>CN(C=O)C>[CH:1]1([C:4]2[CH:5]=[C:6]([C:13]([OH:15])=[O:14])[C:7]3[CH:12]=[N:11][N:10]([CH2:21][CH3:22])[C:8]=3[N:9]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 6340IodoethaneHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 67124108ethyl 6-cyclopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate

Product 1

HCID 167927676-cyclopropyl-1-ethyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl 6-cyclopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate (200 mg, 0.865 mmol) in DMF (10 mL) was carefully added sodium hydride (29.1 mg, 1.211 mmol). After 15 minutes stirring, iodoethane (0.077 mL, 0.951 mmol) was added and the mixture stirred at room temperature for 2 hr. Sodium hydroxide (1 mL, 1.000 mmol) was added and the mixture allowed to stir at room temperature for 1 h. The contents were concentrated in vacuo. The crude residue was diluted with water (50 mL) and acidified with acetic acid. The contents were then extracted with DCM (4×50 mL). The combined organic layers were washed with water, brine, dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (eluent: hexanes to 100% EtOAc, then DCM to 20% MeOH:DCM). The final product was collected as 90 mg (45%). LCMS E-S (M+H)=232.1 1H NMR (400 MHz, DMSO-d6) δ ppm 1.06-1.17 (m, 4H) 1.41 (t, J=7.33 Hz, 3H) 2.35-2.45 (m, 1H) 4.34-4.57 (m, 2H) 7.62 (s, 1H) 8.24 (s, 1H) 13.83 (br. s., 1H). Regiochemical assignment supported by 2D HNMR.

Workup

  1. stirringthe mixture stirred at room temperature for 2 hr
  2. stirringto stir at room temperature for 1 h
  3. concentrationThe contents were concentrated in vacuo
  4. additionThe crude residue was diluted with water (50 mL)
  5. extractionThe contents were then extracted with DCM (4×50 mL)
  6. washThe combined organic layers were washed with water, brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by silica gel chromatography (eluent
  11. customThe final product was collected as 90 mg (45%)

Sources & evidence

ORD record
ord-1bfe8b72cb724f96bd468b3e2d50f6d8
Source dataset
uspto-grants-2014_01
Patent number
US08637509B2

Reaction notes

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