Ammonium Chloride → 3-methyl-1-(2-phenoxy-ethyl)-2-pyridin-3-yl-1H-indole-5-carbonitrile

HRID 1661577Notes

Reaction equation

HRID 1661577 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[NH:4][C:3]=1[C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].Br[CH2:30][CH2:31][O:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[Cl-].[NH4+]>C1COCC1>[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[N:4]([CH2:30][CH2:31][O:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:3]=1[C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 68526Benzene, (2-bromoethoxy)-HCID 3251421Potassium bis(trimethylsilyl)amideHCID 445541323-methyl-2-pyridin-3-yl-1H-indole-5-carbonitrile

Product 1

HCID 582158263-methyl-1-(2-phenoxy-ethyl)-2-pyridin-3-yl-1H-indole-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-methyl-2-pyridin-3-yl-1H-indole-5-carbonitrile (Example 6, 47 mg, 0.20 mmol) in THF (5 mL) at room temperature is added KHMDS (0.5 M in toluene, 0.60 mL, 0.30 mmol) followed with (2-bromo-ethoxy)-benzene (90 mg, 0.45 mmol). The mixture is stirred under N2 for 2 days and aqueous ammonium chloride (1 mL) is added to quench the reaction. The volatiles are removed in vacuo and the residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 1:4 to 1:0) to give 3-methyl-1-(2-phenoxy-ethyl)-2-pyridin-3-yl-1H-indole-5-carbonitrile. 1H NMR (400 MHz, CDCl3) δ ppm 2.25 (s, 3H), 4.10 (t, J=5.2 Hz, 2H), 4.46 (t, J=5.3 Hz, 2H), 6.66 (d, J=7.8 Hz, 2H), 6.93 (t, J=7.3 Hz, 1H), 7.17-7.25 (m, 2H), 7.51-7.57 (m, 2H), 7.59-7.65 (m, 1H), 7.95 (d, J=8.6 Hz, 1H), 7.98 (s, 1H), 8.74-8.79 (m, 2H). HRMS (ESI) m/z 354.1618 [(M+H)+ Calcd for C23H20N3O: 354.1606].

Workup

  1. customto quench
  2. customthe reaction
  3. customThe volatiles are removed in vacuo
  4. customthe residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 1:4 to 1:0)

Sources & evidence

ORD record
ord-0abe0221f5b647e59b4843f91dd271f4
Source dataset
uspto-grants-2011_10
Patent number
US08030334B2

Reaction notes

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