Potassium Fluoride → 5-[1-(ethylsulfonyl)-2,3-dihydro-1H-indol-5-yl]-1-methyl-1H-pyrrole-2-carbonitrile

HRID 2353455Notes

Reaction equation

HRID 2353455 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([S:11]([CH2:14][CH3:15])(=[O:13])=[O:12])[CH2:6][CH2:5]2.[CH3:16][N:17]1[C:21]([C:22]#[N:23])=[CH:20][CH:19]=[C:18]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]>[CH2:14]([S:11]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([C:18]3[N:17]([CH3:16])[C:21]([C:22]#[N:23])=[CH:20][CH:19]=3)=[CH:10][CH:9]=2)[CH2:5][CH2:6]1)(=[O:13])=[O:12])[CH3:15]

Participants

5

Reactant 3

HCID 522689Potassium FluorideHCID 11708078(5-cyano-1-methyl-1H-pyrrol-2-yl)boronic acidHCID 684261415-Bromo-1-(ethylsulfonyl)indoline

Product 1

HCID 250039065-[1-(ethylsulfonyl)-2,3-dihydro-1H-indol-5-yl]-1-methyl-1H-pyrrole-2-carbonitrileYield 59.6%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
25 °C

Procedure

5-Bromo-1-(ethylsulfonyl)indoline (1.85 g, 6.38 mmol), 1-methyl-5-cyano-2-pyrroleboronic acid (1.14 g, 7.7 mmol), KF (1.22 g, 21 mmol), and Pd2(dba)3 (154 mg, 0.16 mmol) were added to a round bottom flask under nitrogen. The flask was sealed and purged with nitrogen for 5 minutes. THF (16 mL) was added followed by a solution of tri-t-butylphosphine (10% wt in hexanes) (0.95 mL, 0.32 mmol) 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-[1-(ethylsulfonyl)-2,3-dihydro-1H-indol-5-yl]-1-methyl-1H-pyrrole-2-carbonitrile (1.2 g) as a colorless oil. MS (EI) m/z 315.8; HPLC purity 99.4% at 210-370 nm, 9.2 min.; the Xterra® RP18 column, 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.

Workup

  1. customThe flask was sealed
  2. custompurged with nitrogen for 5 minutes
  3. additionTHF (16 mL) was added
  4. additionThe mixture was diluted with ethyl acetate
  5. filtrationfiltered through a plug of silica gel
  6. washwashed through with additional ethyl acetate
  7. concentrationconcentrated
  8. customto give a crude brown/black semi-solid
  9. customPurification
  10. customFurther purification via Isco chromatography (the Redisep® column, silica, gradient 50% hexane

Sources & evidence

ORD record
ord-3cc79b8f41664510b02a1f8ef4ce5907
Source dataset
uspto-grants-2010_07
Patent number
US07750038B2

Reaction notes

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