Imidazole → N-[4-[3-cyano-1-ethyl-6-(2-imidazol-1-ylethoxy)indol-2-yl]phenyl]cyclopropanecarboxamide

HRID 252593Notes

Reaction equation

Cl[CH2:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]2[C:8]([C:9]([C:28]#[N:29])=[C:10]([C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([CH:25]4[CH2:27][CH2:26]4)=[O:24])=[CH:18][CH:17]=3)[N:11]2[CH2:14][CH3:15])=[CH:7][CH:6]=1.[Na+].[I-].C([O-])([O-])=O.[K+].[K+].[NH:38]1[CH:42]=[CH:41][N:40]=[CH:39]1>C(#N)C.C(OCC)(=O)C.O>[C:28]([C:9]1[C:8]2[C:12](=[CH:13][C:5]([O:4][CH2:3][CH2:2][N:38]3[CH:42]=[CH:41][N:40]=[CH:39]3)=[CH:6][CH:7]=2)[N:11]([CH2:14][CH3:15])[C:10]=1[C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23]([CH:25]2[CH2:27][CH2:26]2)=[O:24])=[CH:18][CH:17]=1)#[N:29]

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of cyclopropanecarboxylic acid {4-[6-(2-chloroethoxy)-3-cyano-1-ethyl-1H-indol-2-yl]-phenyl}-amide (102 mg, 0.25 mmol) in 1.5 mL of acetonitrile are added NaI (46 mg, 0.275 mmol), K2CO3 (138 mg, 1 mmol) and imidazole (51 mg, 0.75 mmol) in a sealed tube. Then the mixture is heated to 90° C. and stirred overnight. After it is cooled to room temperature, water and ethyl acetate are added. The organic layer is separated, washed with brine (2×), dried over anhydrous Na2SO4, filtered and concentrated. The crude compound is purified by preparative HPLC to give 71% of cyclopropanecarboxylic acid {4-[3-cyano-1-ethyl-6-(2-imidazol-1-yl-ethoxy)-1H-indol-2-yl]-phenyl}-amide.

Workup

temperatureAfter it is cooled to room temperature
customThe organic layer is separated
washwashed with brine (2×)
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude compound is purified by preparative HPLC

Sources & evidence

ORD record: ord-0ab99f66f67743bcaca16b3a87fb9f67
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07868037B2

Reaction notes

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