Sulfuric Acid → 6-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-2-methylpyrido[2,3-b]pyrazin-3(4H)-one

HRID 510099Notes

Reaction equation

HRID 510099 reaction equation
[F:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:19]=[C:18]([NH2:20])[C:17]([NH2:21])=[CH:16][CH:15]=2)=[N:6]1.O=[C:27]([CH3:33])[C:28](OCC)=[O:29].S(=O)(=O)(O)O>C(O)C>[F:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[CH:15]=[CH:16][C:17]3[N:21]=[C:27]([CH3:33])[C:28](=[O:29])[NH:20][C:18]=3[N:19]=2)=[N:6]1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 12041Ethyl pyruvateHCID 666140516-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyridine-2,3-diamine

Product 1

HCID 666141706-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-2-methylpyrido[2,3-b]pyrazin-3(4H)-one

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

146 mg (0.435 mmol) of the compound from example 43A were initially charged in ethanol (8 ml), then 56 mg (0.48 mmol) of ethyl 2-oxopropanoate were added and the reaction mixture was heated to reflux overnight. Thereafter, a catalytic amount of conc. sulfuric acid was added and the mixture was again heated to reflux overnight. Subsequently, the mixture was cooled to RT, and the solid formed was filtered off, washed with ethanol and dried under high vacuum. The crude product was dissolved in DMSO and separated by means of preparative HPLC (eluent: acetonitrile-water with 0.1% formic acid gradient), and the product fractions were concentrated. This gave 30 mg (18% of theory) of the title compound in solid form.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux overnight
  3. temperaturethe mixture was again heated
  4. temperatureto reflux overnight
  5. customthe solid formed
  6. filtrationwas filtered off
  7. washwashed with ethanol
  8. customdried under high vacuum
  9. dissolutionThe crude product was dissolved in DMSO
  10. customseparated by means of preparative HPLC (eluent: acetonitrile-water with 0.1% formic acid gradient)
  11. concentrationthe product fractions were concentrated

Sources & evidence

ORD record
ord-cafb8227206f474aa0c8ec64b166cadc
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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