Iodine → HCID 71464778, compound

HRID 536484Notes

Reaction equation

HRID 536484 reaction equation
N[C:2]1[C:3]2[C:30]([CH3:32])([CH3:31])[C:29](=[O:33])[NH:28][C:4]=2[N:5]=[C:6]([C:8]2[N:9]=[C:10]([CH2:18][C:19]3[C:24]([F:25])=[CH:23][CH:22]=[C:21]([F:26])[C:20]=3[F:27])[N:11]3[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=23)[N:7]=1.[I-:34].[Cs+].II.N(OCCC(C)C)=O>COCCOC.[Cu]I>[Cl:17][C:15]1[CH:14]=[CH:13][C:12]2[N:11]([C:10]([CH2:18][C:19]3[C:24]([F:25])=[CH:23][CH:22]=[C:21]([F:26])[C:20]=3[F:27])=[N:9][C:8]=2[C:6]2[N:7]=[C:2]([I:34])[C:3]3[C:30]([CH3:32])([CH3:31])[C:29](=[O:33])[NH:28][C:4]=3[N:5]=2)[CH:16]=1

Participants

7

Reactant 4

HCID 807Iodine2×HCID 8053Isoamyl Nitrite2×HCID 24601Cesium iodide2×HCID 46223701HCID 46223701, compound2×

Product 1

HCID 71464778HCID 71464778, compoundYield 34.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

556 mg (1.176 mmol) of 4-amino-2-[6-chloro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (described in WO 2010/065275) was put in 1,2-dimethoxyethane (14 ml), and 305 mg (1.176 mmol) of caesium iodide, 149 mg (0.588 mmol) of iodine and 67 mg (0.353 mmol) of copper(I) iodide were added at room temperature. Then isopentyl nitrite (0.933 ml) was added and it was heated overnight to 60° C. Next day, 305 mg (1.176 mmol) of caesium iodide, 149 mg (0.588 mmol) of iodine and 67 mg (0.353 mmol) of copper(I) iodide, and isopentyl nitrite (0.933 ml) were added again and it was heated for 3 days to 60° C. After cooling, it was combined with a smaller batch (starting from 50 mg 4-amino-2-[6-chloro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one). It was extracted with ethyl acetate and saturated aqueous sodium thiosulphate and the phases were separated. The organic phase was extracted twice more with saturated aqueous sodium thiosulphate. Then the organic phase was washed with saturated aqueous sodium chloride solution, dried over sodium sulphate, filtered, concentrated by evaporation and the residue was purified by preparative HPLC (acetonitrile:water (+0.05% formic acid) gradient). 236 mg of the title compound was obtained (31% of theor.).

Workup

  1. temperatureit was heated overnight to 60° C
  2. temperatureit was heated for 3 days to 60° C
  3. temperatureAfter cooling
  4. extractionIt was extracted with ethyl acetate and saturated aqueous sodium thiosulphate
  5. customthe phases were separated
  6. extractionThe organic phase was extracted twice more with saturated aqueous sodium thiosulphate
  7. washThen the organic phase was washed with saturated aqueous sodium chloride solution
  8. dry with materialdried over sodium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated by evaporation
  11. customthe residue was purified by preparative HPLC (acetonitrile:water (+0.05% formic acid) gradient)

Sources & evidence

ORD record
ord-b40b6e6c01424dba8db87e1399a27f25
Source dataset
uspto-grants-2014_10
Patent number
US08859569B2

Reaction notes

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