Potassium Carbonate → 4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzonitrile

HRID 1627253Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:15](=[S:24])[NH:14][CH:13]=2)([CH3:11])[CH3:10])[CH:5]=[CH:6][C:7]=1[Cl:8].Br[CH2:26][C:27]1[C:34]([F:35])=[CH:33][C:30]([C:31]#[N:32])=[CH:29][C:28]=1[F:36].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([C:12]2[N:16]([C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)[C:15]([S:24][CH2:26][C:27]3[C:28]([F:36])=[CH:29][C:30]([C:31]#[N:32])=[CH:33][C:34]=3[F:35])=[N:14][CH:13]=2)([CH3:11])[CH3:10])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

Conditions

Temperature: 56 °C

Procedure

A mixture of 5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2(3H)-thione (760 mg, 2 mmol), 4-(bromomethyl)-3,5-difluorobenzonitrile (464 mg, 2 mmol) and K2CO3 (414 mg, 3 mmol) in acetone (10 mL) was stirred at 56° C. for 4 h. After cooling, the solids were removed by filtration and rinsed with acetone. The combined filtrates were concentrated and purified by flash chromatography, eluting with EtOAc-Hexane (1:1) to afford the title compound (89 mg). 1H NMR (400 MHz, CDCl3) δ 7.26 (t, J=4.2, 2H), 7.17 (d, J=6.5, 2H), 7.03 (d, J=2.2, 1H), 6.88-6.79 (m, 3H), 6.50-6.44 (m, 2H), 4.08 (d, J=9.1, 2H), 2.04 (s, 1H), 1.49 (s, 7H); MS (EI) m/z 432 (MH+).

Workup

temperatureAfter cooling
customthe solids were removed by filtration
washrinsed with acetone
concentrationThe combined filtrates were concentrated
custompurified by flash chromatography
washeluting with EtOAc-Hexane (1:1)

Sources & evidence

ORD record: ord-87b920814df84abbb01f5cf4dccce4e0
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785488B2

Reaction notes

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