Triethylamine → 1H-Indolamine

HRID 966517Notes

Reaction equation

HRID 966517 reaction equation
C(OC([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17](OS(C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)(=O)=O)[CH:18]=2)[NH:13][C:12]=1C)=O)C1C=CC=CC=1.C([N:40](CC)CC)C.CN(CC#C)C.C(OCC)(=O)C.CO.C(N(CC)CC)C>C1COCC1.[Cu]I.C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[NH:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:11]=[C:12]1[NH2:40]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 81643N,N-DimethylpropargylamineHCID 21980445Ethyl acetate methanol triethylamineHCID 23393847HCID 23393847, compound

Product 1

HCID 1220741H-IndolamineYield 62.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

2-Methyl-5-(nonafluorobutane-1-sulfonyloxy)-1H-indole-3-carboxylic acid benzyl ester (0.480 g, 0.85 mmol, 1 eq, Example 52, Step A) was dissolved in dry THF (10 mL) under Ar. Triethylamine (0.223 mL, 1.6 mmol, 2.0 eq) was added followed by the addition of copper (1) iodide (0.008 g, 0.04 mmol, 5 mol %), dichloropalladium (II) bis-diphenylphosphinoferrocene (0.016 g, 0.02 mmol, 2 mol %), and N,N-dimethylpropargylamine (0.184 mL, 1.6 mmol, 2 eq). The reaction mixture was stirred at 80° C. and followed by TLC (ethyl acetate/methanol/triethylamine 87/10/3). After 48 hours, the reaction was loaded on silica gel and chromatographed, (ethyl acetate/methanol/triethylamine 87/10/3). The resulting product was contaminated with bis-alkyne side product, and was further purified using reverse-phase prep-HPLC 10%-1 00% Acetonitrile/water, 0.1% TFA. 0.070 g (18% yield) of the indole-amine was obtained as a brown semisolid: LC/MS (ESI+) 347 (M+1).

Workup

  1. customchromatographed
  2. customwas further purified

Sources & evidence

ORD record
ord-15469e4b1a1d4bd7a32ac78f32e93b0c
Source dataset
uspto-grants-2005_10
Patent number
US06951848B2

Reaction notes

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