2-Chloro-1-(4-methoxybenzyl)-1H-benzo[D]imidazole → 1-(4-methoxybenzyl)-N-(4-(3-(tetrahydro-2H-pyran-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine

HRID 410213Notes

Reaction equation

[O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[C:8]([O:13][C:14]3[CH:20]=[CH:19][C:17]([NH2:18])=[CH:16][CH:15]=3)=[N:9][CH:10]=[CH:11][CH:12]=2)[CH2:3][CH2:2]1.Cl[C:22]1[N:26]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[C:25]2[CH:36]=[CH:37][CH:38]=[CH:39][C:24]=2[N:23]=1>CC(O)C>[CH3:35][O:34][C:31]1[CH:30]=[CH:29][C:28]([CH2:27][N:26]2[C:25]3[CH:36]=[CH:37][CH:38]=[CH:39][C:24]=3[N:23]=[C:22]2[NH:18][C:17]2[CH:16]=[CH:15][C:14]([O:13][C:8]3[C:7]([CH:4]4[CH2:3][CH2:2][O:1][CH2:6][CH2:5]4)=[CH:12][CH:11]=[CH:10][N:9]=3)=[CH:20][CH:19]=2)=[CH:33][CH:32]=1

Participants

Conditions

Temperature: 170 °C

Procedure

A glass microwave reaction vessel was charged with 4-(3-(tetrahydro-2H-pyran-4-yl)pyridin-2-yloxy)aniline (0.2573 g, 0.952 mmol) and 2-chloro-1-(4-methoxybenzyl)-1H-benzo[d]imidazole (0.312 g, 1.142 mmol) in IPA. The reaction mixture was stirred and heated in a Biotage Initiator microwave reactor at 170° C. for 30 min. Solvent was evaporated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage pre-packed silica gel column (40S), eluting with a gradient of 10% to 80% EtOAc in hexane, to provide 1-(4-methoxybenzyl)-N-(4-(3-(tetrahydro-2H-pyran-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine. IC50 (uM) +++++.

Workup

customA glass microwave reaction vessel
customSolvent was evaporated
customchromatographed through a Biotage pre-packed silica gel column (40S)
washeluting with a gradient of 10% to 80% EtOAc in hexane

Sources & evidence

ORD record: ord-9bfc891221654feeb71575c274776c6c
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759532B2

Reaction notes

Loading…