Triethylamine → HCID 9838533, compound

HRID 1604279Notes

Reaction equation

HRID 1604279 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[Sn](C)(C)[C:19]1[CH:20]=[N:21][CH:22]=[N:23][CH:24]=1.C(N(CC)CC)C.[Cl-].[Li+].C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C>CN(C)C=O.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>[CH3:16][N:13]1[CH2:14][CH2:15][CH:11]([C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([C:19]4[CH:20]=[N:21][CH:22]=[N:23][CH:24]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:12]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 314042,6-Di-tert-butyl-4-methylphenolHCID 433294Lithium ChlorideHCID 127998215-Trimethylstannyl-pyrimidineHCID 153262755-bromo-3-(N-methylpyrrolidin-3-yl)1H-indole

Product 1

HCID 9838533HCID 9838533, compoundYield 17.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-bromo-3-(N-methylpyrrolidin-3-yl)-1H-indole (0.450 g, 1.86 mmol), 5-trimethylstannylpyrimidine (0.518 g, 1.86 mmol), bis(triphenylphosphine)palladium(II) chloride (0.100 g), triethylamine (0.84 mL, 6.03 mmol, 3.2 eq), lithium chloride (0.254 g), and 2,6-di-tert-butyl-4-methylphenol (3.0 g) in anhydrous N,N-dimethylformamide (8 mL) was heated at reflux under nitrogen for 4 hours. The resulting reaction mixture was evaporated under reduced pressure, and the residue was column chromatographed using silica gel (approximately 25 g) and elution with 9:1:0.1 [methylene chloride/methanol/ammonium hydroxide] afforded the title compound (0.089 g, 0.32 mmol, 17%) as an off-white solid: mp, 140.0-143.0° C.; TLC Rf =0.20 in 9:1:0.1 [methylene chloride/methanol/ammonium hydroxide]; 1H NMR (CD3OD)δ9.05 (s, 2H), 9.03 (s, 1H), 7.87 (d, J=1.1 Hz, 1H), 7.47 (d, J=8.4 Hz, 1H), 7.39 (dd, J=1.6 and 8.5 Hz, 1H), 7.16 (s, 1H), 4.90 (s, 1 exchangeable H), 3.78-3.66 (m, 1H), 3.16 (t, J=8.7 Hz, 1H), 2.92-2.84 (m, 1H), 2.72-2.59 (m, 2H), 2.42 (s, 3H), 2.42-2.33 (m, 1H), 2.10-1.99 (m, 1H); 13C NMR (CD3OD) d 156.6, 155.9, 138.9, 137.7, 129.0, 125.4, 123.2, 121.4, 119.7, 118.7, 113.6, 63.5, 57.1, 42.6, 36.3, 33.2; FAB LRMS (m/z, relative intensity) 279 ([MH]+, 100); HRMS calculated for C17H18N4 278.1533, found 278.1520.

Workup

  1. temperaturewas heated
  2. temperatureat reflux under nitrogen for 4 hours
  3. customThe resulting reaction mixture
  4. customwas evaporated under reduced pressure
  5. customchromatographed
  6. washsilica gel (approximately 25 g) and elution with 9:1:0.1 [methylene chloride/methanol/ammonium hydroxide]

Sources & evidence

ORD record
ord-b6e2ba63cab943b9b4ca163fcd59e535
Source dataset
uspto-grants-1999_11
Patent number
US05994352

Reaction notes

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