Selectfluor → 2-cyclopropyl-5-[6-(2-fluoro-3,5-dimethoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]isoindolin-1-one

HRID 1778794Notes

Reaction equation

HRID 1778794 reaction equation
[B-](F)(F)(F)F.[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+]([F:21])(CC2)C1.[CH:22]1([N:25]2[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[C:30]([C:34]4[C:42]5[C:37](=[N:38][C:39]([C:43]6[CH:48]=[C:47]([O:49][CH3:50])[CH:46]=[C:45]([O:51][CH3:52])[CH:44]=6)=[CH:40][CH:41]=5)[N:36]([CH:53]5[CH2:58][CH2:57][CH2:56][CH2:55][O:54]5)[N:35]=4)[CH:31]=3)[C:26]2=[O:59])[CH2:24][CH2:23]1>C(#N)C>[CH:22]1([N:25]2[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[C:30]([C:34]4[C:42]5[C:37](=[N:38][C:39]([C:43]6[CH:48]=[C:47]([O:49][CH3:50])[CH:46]=[C:45]([O:51][CH3:52])[C:44]=6[F:21])=[CH:40][CH:41]=5)[N:36]([CH:53]5[CH2:58][CH2:57][CH2:56][CH2:55][O:54]5)[N:35]=4)[CH:31]=3)[C:26]2=[O:59])[CH2:23][CH2:24]1

Participants

4

Reactant 2

HCID 2724933SelectfluorHCID 867228732-cyclopropyl-5-[6-(3,5-dimethoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]isoindolin-1-one

Product 1

HCID 867228742-cyclopropyl-5-[6-(2-fluoro-3,5-dimethoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]isoindolin-1-oneYield 78.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-(Chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane ditetrafluoroborate (0.21 g, 0.59 mmol) was added to a stirring solution of 2-cyclopropyl-5-[6-(3,5-dimethoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]isoindolin-1-one (0.15 g, 0.29 mmol) in acetonitrile (3 mL). The mixture was stirred at r.t. for 2 h. Then it was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-50%) to afford the desired product (0.12 g). LCMS (M+H)+=529.2.

Workup

  1. concentrationThen it was concentrated under reduced pressure
  2. customThe residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-50%)

Sources & evidence

ORD record
ord-d5a9150e689e4e2da7849e3be458c227
Source dataset
uspto-grants-2016_02
Patent number
US09266892B2

Reaction notes

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