Methyl Ethyl Ketone → 2-(4-aminophenyl)-1-cyclobutyl-6-(2-methoxyethoxy)-1H-indole-3-carbonitrile

HRID 502249Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:20]3[CH2:23][CH2:22][CH2:21]3)[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([OH:19])[CH:11]=3)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].C(C(C)=O)C.[CH3:35][O:36][CH2:37][CH2:38]Br>CN(C=O)C>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:20]3[CH2:21][CH2:22][CH2:23]3)[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][CH2:38][CH2:37][O:36][CH3:35])[CH:11]=3)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 85 °C

Procedure

To a suspension of 2-(4-aminophenyl)-1-cyclobutyl-6-hydroxy-1H-indole-3-carbonitrile (519.2 mg, 1.71 mmol), K2CO3, 10 mL of methyl ethyl ketone, and 2 mL of DMF is added 2-bromoethyl methyl ether. The resulting mixture is stirred at 85° C. for 8 h. The mixture is concentrated and the residue is partitioned between ethyl acetate (20 mL) and water (20 mL). The aqueous phase is extracted with additional ethyl acetate (20 mL). The combined organic phases are washed with saturated NaCl, dried over MgSO4, and then the solution is concentrated and the product is washed with diethyl ether to afford 505.0 mg (81.7% yield) of 2-(4-aminophenyl)-1-cyclobutyl-6-(2-methoxy-ethoxy)-1H-indole-3-carbonitrile as a yellow solid.

Workup

concentrationThe mixture is concentrated
customthe residue is partitioned between ethyl acetate (20 mL) and water (20 mL)
extractionThe aqueous phase is extracted with additional ethyl acetate (20 mL)
washThe combined organic phases are washed with saturated NaCl
dry with materialdried over MgSO4
concentrationthe solution is concentrated
washthe product is washed with diethyl ether

Sources & evidence

ORD record: ord-e393fe5021b6475b9e2fd1967393620d
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772271B2

Reaction notes

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