2-(4-ethoxyphenyl)acetyl Chloride → 1-(cyclopropylmethyl)-2-(4-ethoxybenzyl)-1H-benzimidazole-5-carbonitrile

HRID 1796476Notes

Reaction equation

HRID 1796476 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11](Cl)=O)=[CH:6][CH:5]=1)[CH3:2].[NH2:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[NH:23][CH2:24][CH:25]1[CH2:27][CH2:26]1)[C:18]#[N:19]>C(O)(=O)C>[CH:25]1([CH2:24][N:23]2[C:22]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][C:15]=3[N:14]=[C:11]2[CH2:10][C:7]2[CH:8]=[CH:9][C:4]([O:3][CH2:1][CH3:2])=[CH:5][CH:6]=2)[CH2:26][CH2:27]1

Participants

4

Reactant 2

HCID 116297822-(4-ethoxyphenyl)acetyl ChlorideHCID 221813993-amino-4-[(Cyclopropylmethyl)amino]benzonitrile

Product 1

HCID 221813091-(cyclopropylmethyl)-2-(4-ethoxybenzyl)-1H-benzimidazole-5-carbonitrileYield 78.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Following the general procedure 2D, the freshly prepared (4-ethoxyphenyl)acetyl chloride (from 793 mg of acid, 4.4 mmol) and crude 3-amino-4-[(cyclopropylmethyl)amino]benzonitrile (750 mg, 4.01 mmol) were heated in acetic acid (HOAc) overnight. After work-up, the crude residue was purified by silica gel column chromatography to afford pure product (1.04 g, 78%) as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.50 (d, J=8.4 Hz, 1H), 7.38 (d, J=8.4 Hz, 1H), 7.14 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.4 Hz, 2H), 4.29 (s, 2H), 4.01 (d, J=7.6 Hz, 2H), 3.96 (q, J=7.6 Hz, 2H), 1.39 (t, J=7.6 Hz, 3H), 1.04–1.00 (m, 1H), 0.58–0.53 (m, 2H), 0.29–0.25 (m, 2H). MS (ESI) (M+H)+=332. Anal. Calcd for C21H21N3O.0.1H2O: C, 75.50; H, 6.41; N, 12.61. Found: C, 75.76; H, 6.72; N, 12.45.

Workup

  1. customAfter work-up, the crude residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d677addfd7ca4eef903a087981ec37cb
Source dataset
uspto-grants-2006_04
Patent number
US07030139B2

Reaction notes

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