Ethyl Acetate → HCID 66733853, compound

HRID 1929712Notes

Reaction equation

HRID 1929712 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH3:18])=[N:15][C:16](I)=[C:10]2[CH:9]1[CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:31]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C[CH:32]=1.C([Sn](CCCC)(CCCC)C=C)CCC.CC(=O)OCC>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH3:18])=[N:15][C:16]([CH:31]=[CH2:32])=[C:10]2[CH:9]1[CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11776TriphenylphosphineHCID 81998TributylvinyltinHCID 66734096HCID 66734096, compound

Product 1

HCID 66733853HCID 66733853, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A slightly yellow homogeneous solution of 1-iodo-3-methyl-8-[2-(4-trifluoromethyl-phenyl)-ethyl]-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester (1.500 g; 2.802 mmol) in anhydrous DMF (15 ml) was treated successively at rt with tris(dibenzylideneacetone)dipalladium(0) (82 mg; 0.090 mmol), triphenylphosphine (91 mg; 0.350 mmol), and finally with tributyl(vinyl)tin (1.63 ml; 5.604 mmol). The resulting mixture was heated to 90° C., under nitrogen, for 20 h. The reaction mixture was cooled to rt, EA (200 ml) was added, and the resulting solution was washed with water (2×125 ml). The resulting yellow organic layer was dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure to give an orange oil. Purification by FC (DCM/MeOH=40/1) gave the pure product 3-methyl-8-[2-(4-trifluoromethyl-phenyl)-ethyl]-1-vinyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester as a yellow solid (0.936 g; 77%). LC-MS: tR=0.88 min.; [M+H]+=436.48 g/mol.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. washthe resulting solution was washed with water (2×125 ml)
  3. dry with materialThe resulting yellow organic layer was dried over anh. MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure
  6. customto give an orange oil
  7. customPurification by FC (DCM/MeOH=40/1)

Sources & evidence

ORD record
ord-19c1c0bd847b416d8f00b5d5be70d3fa
Source dataset
uspto-grants-2012_05
Patent number
US08188082B2

Reaction notes

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