Triethylamine → 5-(5-Cyanopyrid-3-yl)-3-(N-methylpyrrolidin-3-yl)-1H-indole

HRID 2289852Notes

Reaction equation

HRID 2289852 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12]1.[C:17]([C:19]1[CH:20]=[C:21]([Sn](C)(C)C)[CH:22]=[N:23][CH:24]=1)#[N:18].C(N(CC)CC)C.[Cl-].[Li+].C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:17]([C:19]1[CH:20]=[C:21]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[C:5]3[CH:11]2[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12]2)[CH:22]=[N:23][CH:24]=1)#[N:18]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 314042,6-Di-tert-butyl-4-methylphenolHCID 433294Lithium ChlorideHCID 153262755-bromo-3-(N-methylpyrrolidin-3-yl)1H-indoleHCID 186990455-(Trimethylstannyl)nicotinonitrile

Product 1

HCID 154342745-(5-Cyanopyrid-3-yl)-3-(N-methylpyrrolidin-3-yl)-1H-indoleYield 11.2%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Procedure

A mixture of 5-bromo-3-(N-methylpyrrolidin-3-yl)-1H-indole (0.500 g, 1.79 mmol), 5-cyano-3-trimethylstannylpyridine (0.525 g, 1.97 mmol, 1.1 eq), bis(triphenylphosphine)palladium(II) chloride (0.628 g, 0.90 mmol, 0.5 eq), triethylamine (1.19 mL, 8.59 mmol, 4.8 eq), lithium chloride (0.235 g, 5.55 mmol, 3.1 eq), and 2,6-di-tert-butyl-4-methylphenol (40 mg) in anhydrous acetontrile (5 mL) was heated at reflux under nitrogen for 20 hours. The resulting reaction mixture was evaporated under reduced pressure, and the residue was column chromatographed using silica gel (approx 50 g) and elution with 9:1:0.1 [methylene chloride/methanol/ammonium hydroxide] to afford the title compound (0.060 g, 0.20 mmol, 11%) as a clear, pale brown oil: LRMS (m/z, relative intensity) 302 (M+, 29), 245 (8), 57 (100); HRMS calculated for C19H18N4 302.1528, found 302.1533.

Workup

  1. temperaturewas heated
  2. temperatureat reflux under nitrogen for 20 hours
  3. customThe resulting reaction mixture
  4. customwas evaporated under reduced pressure
  5. customchromatographed
  6. washsilica gel (approx 50 g) and elution with 9:1:0.1 [methylene chloride/methanol/ammonium hydroxide]

Sources & evidence

ORD record
ord-002dc5df19d74d2bb1d0e1c308b35df5
Source dataset
uspto-grants-2000_07
Patent number
US06093822

Reaction notes

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