3-Cyanobenzoyl chloride → Ammonium Hydroxide

HRID 593519Notes

Reaction equation

HRID 593519 reaction equation
Cl.[CH3:2][C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][C:4]=1[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[C:28]([C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=1)[C:33](Cl)=[O:34])#[N:29]>C1COCC1>[NH4+:5].[OH-:34].[CH3:2][C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C:33]([C:32]2[CH:31]=[C:30]([CH:38]=[CH:37][CH:36]=2)[C:28]#[N:29])=[O:34])[C:4]=1[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 3

HCID 3084833-Cyanobenzoyl chlorideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 445539613-Methyl-2-(3-pyridyl)indole hydrochloride

Product 2

HCID 14923Ammonium HydroxideYield 0.1%HCID 582156123-(3-Methyl-2-pyridin-3-yl-indole-1-carbonyl)-benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A flask is charged with 3-methyl-2-pyridin-3-yl-1H-indole hydrochloride (Example 1, 0.100 g, 0.408 mmol) in THF (2.5 mL) and cooled to 0° C. KHMDS (0.5 M in toluene, 1.8 mL, 0.898 mmol) is added and the mixture is stirred at room temperature for 30 min, followed by addition of 3-cyano-benzoyl chloride (0.135 g, 0.817 mmol). The reaction mixture is stirred for 0.5 h, then quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is purified by reverse phase HPLC with Xbridge Shield RP18 column and a 0.1% aqueous NH4OH in acetonitrile gradient to afford 3-(3-methyl-2-pyridin-3-yl-indole-1-carbonyl)-benzonitrile product as a yellow solid. 1H NMR (400 MHz, MeOD) δ ppm 2.31 (s, 3H), 7.32 (ddd, J=7.9, 4.9, 0.9 Hz, 1H), 7.37-7.44 (m, 2H), 7.66-7.70 (m, 4H), 7.71-7.76 (m, 2H), 7.85-7.91 (m, 1H), 8.37 (dd, J=5.1, 1.5 Hz, 1H), 8.46 (dd, J=2.3, 0.8 Hz, 1H). HRMS (ESI) m/z 338.1293 [(M+H)+ Calcd for C22H16N3O: 338.1293].

Workup

  1. stirringThe reaction mixture is stirred for 0.5 h
  2. customquenched with saturated ammonium chloride
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by reverse phase HPLC with Xbridge Shield RP18 column

Sources & evidence

ORD record
ord-afe8ee17251a459c9aecf12b334c1a27
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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