Dimethylformamide → 2-butyl-4-[4-(4-ethyl-hexyloxy)-phenyl]-1-[4-(4-methoxy-naphthalen-1-yl-oxy)-phenyl]-1H-imidazole

HRID 901707Notes

Reaction equation

C(N(CC)[CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14](=O)[CH3:15])=[CH:10][CH:9]=1)C.[CH2:19]1[CH2:24][NH:23][C:21](=O)[CH2:20]1.Br[Br-]Br.[CH3:28][O:29][C:30]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:33]([O:40][C:41]2[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=2)=[CH:32][CH:31]=1.[CH3:48]N(C=O)C.Br[CH2:54][C:55]([C:57]1C=CC(OCCCN(CC)CC)=[CH:59][CH:58]=1)=O>CO.O.CCOC(C)=O>[CH2:19]([C:24]1[N:45]([C:44]2[CH:43]=[CH:42][C:41]([O:40][C:33]3[C:34]4[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=4)[C:30]([O:29][CH3:28])=[CH:31][CH:32]=3)=[CH:47][CH:46]=2)[CH:15]=[C:14]([C:11]2[CH:10]=[CH:9][C:8]([O:7][CH2:6][CH2:5][CH2:4][CH:57]([CH2:58][CH3:59])[CH2:55][CH3:54])=[CH:13][CH:12]=2)[N:23]=1)[CH2:20][CH2:21][CH3:48]

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of 1-{4-[3-(diethylamino)propoxy]phenyl}ethanone (2.3 mmol) in anhydrous MeOH (5 mL) at 0° C., pyrrolidone hydrotribromide (1.2 eq., 2.7 mmol) was added, according to General Procedure R1. The reaction mixture was stirred under nitrogen at 0° C. for 1 h and was allowed to warm to rt until completion, as indicated by TLC or HPLC. The solvent was then removed in vacuuo and the crude 2-bromo-1-{4-[3-(diethylamino)propoxy]phenyl}ethanone was used for further transformation. To a stirred solution of 4-(4-methoxy-naphthalen-1-yloxy)aniline (1.2 eq., 2.5 mmol) in anhydrous DMF (5 mL) DIEA (3 eq. 7.5 mmol) was added, followed by slow addition of the 2-bromo-1-{4-[3-(diethylamino)propoxy]phenyl}ethanone described above (2.3 mmol), according to General Procedure R2. The reaction mixture was stirred under nitrogen at rt until completion, as indicated by TLC or HPLC. The reaction mixture was then diluted with cold H2O and the product was isolated in EtOAc. The combined organic layers were washed with brine and dried over sodium sulfate. Evaporation of solvent in vacuuo afforded the desired product. The crude alkylated aniline was used for further transformation.

Workup

temperatureto warm to rt until completion
customThe solvent was then removed in vacuuo
stirringThe reaction mixture was stirred under nitrogen at rt until completion
washThe combined organic layers were washed with brine
dry with materialdried over sodium sulfate
customEvaporation of solvent in vacuuo

Sources & evidence

ORD record: ord-2c9d9c510ffd4b41910619c6875df482
Source dataset: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07361678B2

Reaction notes

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