Water → 8-Fluoro-6-(4-fluoro-phenyl)-10-trifluoromethyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one

HRID 925798Notes

Reaction equation

HRID 925798 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[C:8]2[N:7]3[CH2:18][CH2:19][NH:20][C:21](=[O:22])[C:6]3=[CH:5][C:4]=2[CH:3]=1.CN(C)CCN(C)C.[F:31][C:32]([F:35])([F:34])I.O>C(#N)C.CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[C:8]2[N:7]3[CH2:18][CH2:19][NH:20][C:21](=[O:22])[C:6]3=[C:5]([C:32]([F:35])([F:34])[F:31])[C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 16843TrifluoroiodomethaneHCID 900360598-Fluoro-6-(4-fluoro-phenyl)-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one

Product 1

HCID 733353128-Fluoro-6-(4-fluoro-phenyl)-10-trifluoromethyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-oneYield 34%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 8-fluoro-6-(4-fluoro-phenyl)-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (example 18) (0.1 g, 0.335 mmol) in acetonitrile (1 ml) and DMF (1 ml), N,N,N′,N′-tetra-methylethylenediamine (77.9 mg, 101 μl, 670 μmol) and tris(2,2′-biryridyl)ruthenium(II)-chloride hexahydrate (5.02 mg, 6.7 μmol) were added at room temperature. The vial was sealed, cooled to −78° C., and with the help of a needle trifluoroiodomethane (˜0.5 ml) was condensed into the reaction tube. A high lumen (6500K) cool daylight lamp was positioned in front of the reaction vial and the reaction was allowed to stir for 40 h at room temperature. The reaction mixture was poured into water (30 ml) and extracted with ethyl acetate (2×40 ml). The combined organic layers were washed with brine (30 ml), dried (MgSO4) and evaporated. The crude product was further purified by flash chromatography on silica gel (heptane/ethyl acetate 20-80%) and trituration (diethyl ether/heptane) to yield the title compound as a white solid (42 mg, 34%), MS (ISP) m/z=367.4 [(M+H)+], mp 193° C.

Workup

  1. customThe vial was sealed
  2. customcondensed into the reaction tube
  3. extractionextracted with ethyl acetate (2×40 ml)
  4. washThe combined organic layers were washed with brine (30 ml)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe crude product was further purified by flash chromatography on silica gel (heptane/ethyl acetate 20-80%) and trituration (diethyl ether/heptane)

Sources & evidence

ORD record
ord-94dd26d97c044938892eb808e11decac
Source dataset
uspto-grants-2016_03
Patent number
US09284321B2

Reaction notes

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