Potassium Fluoride → HCID 68426073, compound

HRID 2353450Notes

Reaction equation

HRID 2353450 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH2:6][CH2:5]2.[CH3:11][N:12]1[C:16]([C:17]#[N:18])=[CH:15][CH:14]=[C:13]1B(O)O.[F-].[K+]>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]>[NH:7]1[C:8]2[C:4](=[CH:3][C:2]([C:13]3[N:12]([CH3:11])[C:16]([C:17]#[N:18])=[CH:15][CH:14]=3)=[CH:10][CH:9]=2)[CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 522689Potassium FluorideHCID 34115665-BromoindolineHCID 11708078(5-cyano-1-methyl-1H-pyrrol-2-yl)boronic acid

Product 1

HCID 68426073HCID 68426073, compoundYield 35.8%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
25 °C

Procedure

5-Bromoindoline (0.59 g, 3.0 mmol), 1-methyl-5-cyano-2-pyrroleboronic acid (0.54 g, 3.6 mmol), potassium fluoride (KF—0.57 g, 9.9 mmol), and Pd2(dba)3 (72 mg, 0.075 mmol) were added to a round bottom flask under nitrogen. The flask was sealed and purged with nitrogen for 5 minutes. Tetrahydrofuran (THF—7.5 mL) was added and the mixture was purged with nitrogen for an additional 5 minutes. A solution of tri-t-butylphosphine (10% wt in hexanes, 0.45 mL, 0.15 mmol) was added via syringe and the mixture was stirred vigorously at 25° C. for 5 hours. The mixture was diluted with ethyl acetate, filtered through a plug of silica gel, washed through with additional ethyl acetate and concentrated to give a crude brown/black semi-solid. Purification was performed using Isco chromatography (the Redisep® column, silica, gradient 10-60% ethyl acetate in hexane). Further purification via Isco chromatography (the Redisep® column, silica, gradient 50% hexane:45% methylene chloride:5% ethyl acetate) afforded 5-(2,3-dihydro-1H-indol-5-yl)-1-methyl-1H-pyrrole-2-carbonitrile (0.24 g) as a white solid. HPLC purity 100.0% at 210-370 nm, 8.5 min.; the Xterra® column RP18, 3.5μ, 150×4.6 mm column, 1.2 mL/min, 85/15-5/95 (Ammonium formate buffer pH=3.5 acetonitrile+MeOH) for 10 minutes, hold 4 minutes. HRMS: calcd for C14H13N3+H+, 224.11822; found (ESI, [M+H]+), 224.1188;

Workup

  1. customThe flask was sealed
  2. custompurged with nitrogen for 5 minutes
  3. additionTetrahydrofuran (THF—7.5 mL) was added
  4. customthe mixture was purged with nitrogen for an additional 5 minutes
  5. additionA solution of tri-t-butylphosphine (10% wt in hexanes, 0.45 mL, 0.15 mmol) was added via syringe
  6. additionThe mixture was diluted with ethyl acetate
  7. filtrationfiltered through a plug of silica gel
  8. washwashed through with additional ethyl acetate
  9. concentrationconcentrated
  10. customto give a crude brown/black semi-solid
  11. customPurification
  12. customFurther purification via Isco chromatography (the Redisep® column, silica, gradient 50% hexane

Sources & evidence

ORD record
ord-472e8b6e643545c9b226b025f1404288
Source dataset
uspto-grants-2010_07
Patent number
US07750038B2

Reaction notes

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