Ethanol → HCID 67196418, compound

HRID 1423022Notes

Reaction equation

HRID 1423022 reaction equation
Cl[C:2]1[C:3]2[N:4]([C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[N:9][CH:10]=2)[CH:5]=[CH:6][N:7]=1.CCN([CH:24]([CH3:26])C)C(C)C.[C]=[O:28].[CH2:29]([OH:31])C>[Cl-].[Na+].O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[CH2:24]([O:28][C:29]([C:2]1[C:3]2[N:4]([C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[N:9][CH:10]=2)[CH:5]=[CH:6][N:7]=1)=[O:31])[CH3:26]

Participants

7

Reactant 4

HCID 702EthanolHCID 81531DiisopropylethylamineHCID 86672831HCID 86672831, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 67196418HCID 67196418, compound

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 8-chloro-3-(4-fluorophenyl)-imidazo[1,5-a]pyrazine (612 mg, 2.47 mmol), DIPEA (500 μL, 2.9 mmol), Pd[PhCN]2Cl2 (25 mg, 0.07 mmol), and dppf (50 mg, 0.09 mmol) in absolute ethanol (10 mL) in a pressure reactor with stirring and placed under 15 bars of carbon monoxide is warmed at 80° C. After 24 hours, the mixture is cooled to room temperature, returned to atmopheric pressure and opened. The mixture is diluted with brine (100 mL) and extracted with EtOAc (3×40 mL). The combined organic layers are washed with brine (3×25 mL), dried over magnesium sulfate, filtered and concentrated. The residue is passed through a pad of silica gel using dichloromethane-heptane (1:1) to load the sample and then eluting with dichloromethane-heptane (1:1, then 75:25, then 100:0) and then EtOAc-dichloromethane (2:8, then 1:1) to afford 3-(4-fluorophenyl)-imidazo[1,5-a]pyrazine-8-carboxylic acid ethyl ester.

Workup

  1. temperaturethe mixture is cooled to room temperature
  2. extractionextracted with EtOAc (3×40 mL)
  3. washThe combined organic layers are washed with brine (3×25 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washeluting with dichloromethane-heptane (1:1

Sources & evidence

ORD record
ord-74a4834344bd4665a5a7c5644cd37413
Source dataset
uspto-grants-2015_01
Patent number
US08927550B2

Reaction notes

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