Potassium Carbonate → HCID 67975593, compound

HRID 2046236Notes

Reaction equation

HRID 2046236 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:15](I)=[C:9]2[C:10](=[O:14])[NH:11][CH2:12][CH2:13][N:8]2[N:7]=1)=[O:5])[CH3:2].[CH3:17]B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:15]([CH3:17])=[C:9]2[C:10](=[O:14])[NH:11][CH2:12][CH2:13][N:8]2[N:7]=1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 139377Methylboronic AcidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 679916203-Iodo-4-oxo-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester

Product 1

HCID 67975593HCID 67975593, compoundYield 58.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
90 °C

Procedure

Palladium (II) acetate (38 mg, 0.17 mmol) was added to a solution of 3-iodo-4-oxo-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester (0.56 g 1.68 mmol), methylboronic acid (0.75 g, 12.6 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triiso-propyl-1,1′-biphenyl (0.16 mg, 0.34 mmol) and potassium carbonate (0.69 g, 5.0 mmol) in toluene (15 mL) under nitrogen and the mixture was heated at 90° C. for 16 hours. Then the mixture was heated at 120° C. for 4 hours more. The mixture was diluted with a saturated Na2CO3 solution and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvent evaporated in vacuo. The crude product was purified by flash column chromatography (silica; MeOH in DCM 0/100 to 10/90). The desired fractions were collected and the solvents evaporated in vacuo to yield 3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazine-2-carboxylic acid ethyl ester (0.22 g, 58% yield).

Workup

  1. temperatureThen the mixture was heated at 120° C. for 4 hours more
  2. extractionextracted with DCM
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent evaporated in vacuo
  7. customThe crude product was purified by flash column chromatography (silica; MeOH in DCM 0/100 to 10/90)
  8. customThe desired fractions were collected
  9. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-beb72d1493d945f8a007fe14f4cab420
Source dataset
uspto-grants-2013_11
Patent number
US08592422B2

Reaction notes

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