Diethyl Malonate → HCID 178470166, compound

HRID 383561Notes

Reaction equation

HRID 383561 reaction equation
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5]CC)=O.[O-]CC.[Na+].[F:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=1[N:24]1[C:28]([NH2:29])=[C:27]([N:30]=O)[CH:26]=[N:25]1>CCO>[F:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([F:16])[C:18]=1[N:24]1[C:28]2=[N:29][C:3]([OH:5])=[C:2]([C:1]([O:9][CH2:10][CH3:11])=[O:8])[N:30]=[C:27]2[CH:26]=[N:25]1

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 2723922Sodium ethoxideHCID 86652997HCID 86652997, compound

Product 1

HCID 178470166HCID 178470166, compoundYield 58.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a solution of diethyl malonate (4.1 mL, 27 mmol) in 10.0 mL of EtOH at RT was added sodium ethoxide (10 mL of the 21% wt. in denatured ethyl alcohol, 28 mmol) followed by 5 min later, the addition of 1-(2,6-difluorophenyl)-4-nitroso-1H-pyrazol-5-amine (5.13 g, 23 mmol) as a solid. The resulting mixture was refluxed for 4 h. The volatiles were removed under reduced pressure and the remaining residue was partitioned between 50 mL of EtOAc and 30 mL of saturated NH4Cl solution. The precipitated rusty solid was filtered, rinsed with 2×5 mL of water followed by 2×10 mL of EtOAc. The rusty solid was dried in vacuum oven at 45° C. for 4 h to provide 4.3 g of ethyl 1-(2,6-difluorophenyl)-6-hydroxy-1H-pyrazolo[3,4-b]pyrazine-5-carboxylate. The filtrate was transferred to a separatory funnel. The EtOAc layer was separated and washed with brine, dried and concentrated. Purification of the dark brown residue on a silical gel column (25-65% EtOAc in Hexanes) afforded 1.1 g of ethyl 1-(2,6-difluorophenyl)-6-hydroxy-1H-pyrazolo[3,4-b]pyrazine-5-carboxylate as a brown solid. MS (ES+): 321.1 (M+H)+. MS (ES+): 343.0 (M+Na)+.

Workup

  1. temperatureThe resulting mixture was refluxed for 4 h
  2. customThe volatiles were removed under reduced pressure
  3. customthe remaining residue was partitioned between 50 mL of EtOAc and 30 mL of saturated NH4Cl solution
  4. filtrationThe precipitated rusty solid was filtered
  5. washrinsed with 2×5 mL of water
  6. customThe rusty solid was dried in vacuum oven at 45° C. for 4 h

Sources & evidence

ORD record
ord-6177bbc3f0e24936a819e7a80afd1b1b
Source dataset
uspto-grants-2013_02
Patent number
US08367671B2

Reaction notes

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