Potassium Fluoride → 5-(7'-fluoro-2'-oxo-1,2'-dihydrospiro[cyclopropane-1,3'-indol]-5'-yl)-1-methyl-1H-pyrrole-2-carbonitrile

HRID 2250526Notes

Reaction equation

HRID 2250526 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[NH:7][C:6](=[O:12])[C:5]12[CH2:14][CH2:13]1.[CH3:15][N:16]1[C:20]([C:21]#[N:22])=[CH:19][CH:18]=[C:17]1B(O)O.[F-].[K+]>>[F:11][C:9]1[CH:10]=[C:2]([C:17]2[N:16]([CH3:15])[C:20]([C:21]#[N:22])=[CH:19][CH:18]=2)[CH:3]=[C:4]2[C:8]=1[NH:7][C:6](=[O:12])[C:5]12[CH2:14][CH2:13]1

Participants

4

Reactant 3

HCID 522689Potassium FluorideHCID 11708078(5-cyano-1-methyl-1H-pyrrol-2-yl)boronic acidHCID 602091735'-Bromo-7'-fluorospiro[cyclopropane-1,3'-indolin]-2'-one

Product 1

HCID 115292585-(7'-fluoro-2'-oxo-1,2'-dihydrospiro[cyclopropane-1,3'-indol]-5'-yl)-1-methyl-1H-pyrrole-2-carbonitrileYield 83%

Conditions

Temperature
25 °C

Procedure

5′-Bromo-7′-fluorospiro[cyclopropane-1,3′-indol]-2′(1′H)-one (0.60 g, 2.3 mmol), 1-methyl-5-cyano-2-pyrroleboronic acid (0.63 g, 4.2 mmol), KF (0.44 g, 7.6 mmol), and Pd2(dba)3 monochloroform adduct (60 mg, 0.058 mmol) were added to a vial and then purged with nitrogen. THF (5.5 mL) was added and the mixture was purged with nitrogen for 5 min. A solution of tri-t-butylphosphine (10% wt in hexanes) (0.342 mL, 0.115 mmol) was added via syringe and the mixture was stirred vigorously at 25° C. for 2.5 h. The mixture was diluted with 100 mL of EtOAc and filtered through a plug of silica gel and concentrated. Purification by flash chromatography (25% acetone/hexane) afforded the title compound (0.53 g, 83%) as a white solid. MP 228-231° C.

Workup

  1. customthen purged with nitrogen
  2. additionTHF (5.5 mL) was added
  3. customthe mixture was purged with nitrogen for 5 min
  4. additionA solution of tri-t-butylphosphine (10% wt in hexanes) (0.342 mL, 0.115 mmol) was added via syringe
  5. additionThe mixture was diluted with 100 mL of EtOAc
  6. filtrationfiltered through a plug of silica gel
  7. concentrationconcentrated
  8. customPurification by flash chromatography (25% acetone/hexane)

Sources & evidence

ORD record
ord-a99fbb46fc4c4b9a88f99e26565cfd0a
Source dataset
uspto-grants-2008_01
Patent number
US07317037B2

Reaction notes

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