Indole → 1-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]1H-indole

HRID 2264685Notes

Reaction equation

HRID 2264685 reaction equation
I[C:2]1[CH:16]=[CH:15][C:5]([O:6][CH2:7][CH2:8][CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[NH:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[Cu]I.N[C@@H]1CCCC[C@H]1N>[N:10]1([CH2:9][CH2:8][CH2:7][O:6][C:5]2[CH:15]=[CH:16][C:2]([N:17]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH:19]=[CH:18]3)=[CH:3][CH:4]=2)[CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

7

Reactant 3

HCID 798IndoleHCID 62657Potassium Phosphate, TribasicHCID 22325891-[3-(4-Iodophenoxy)propyl]pyrrolidine

Product 1

HCID 166619451-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]1H-indoleYield 35%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 438061,2-Diaminocyclohexane, trans-CatalystHCID 312751,4-DioxaneSolvent

Procedure

1-[3-(4-Iodophenoxy)propyl]-pyrrolidine (66 mg, 0.2 mmol), indole (28 mg, 0.24 mmol), copper(I) iodide (0.4 mg, 0.002 mmol), trans-1,2-diaminocyclohexane (0.0024 mmol, 0.02 mmol), and potassium phosphate tribasic (89 mg, 0.42 mmol) were stirred at 90° C. in dioxane overnight. The reaction mixture was filtered through celite and washed with dichloromethane. The filtrate was concentrated, and the resulting residue was purified by semi-prep LC-MS to give 22.4 mg of the desired product (35% yield). LC-MS (C21H24N2O calc'd 320) m/z 321 (M+H); 1H NMR (300 MHz, CDCl3) d 7.67 (d, J=6.9 Hz, 1H), 7.45 (d, J=8.4 Hz, 1H), 7.40-7.35 (m, 2H), 7.27 (d, J=3 Hz, 1H), 7.22-7.10 (m, 2H), 7.04-6.99 (m, 2H), 6.64 (d, J=3 Hz, 1H), 4.08 (t, J=6.3 Hz, 2H), 2.66 (t, J=7.2 Hz, 2H), 2.57-2.52 (m, 4H), 2.09-2.00 (m, 2H), 1.83-1.78 (m, 4H).

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. washwashed with dichloromethane
  3. concentrationThe filtrate was concentrated
  4. customthe resulting residue was purified by semi-prep LC-MS

Sources & evidence

ORD record
ord-c82eacd206334aebbde2863adab62d24
Source dataset
uspto-grants-2010_12
Patent number
US07855224B2

Reaction notes

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