2-Methoxy-N-methylaniline → 4-Chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-N-(2-methoxy-phenyl)-N-methyl-benzamide

HRID 448940Notes

Reaction equation

[O:1]([C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[NH:5][CH3:6])[CH3:2].[Al](CC)(CC)CC.CO[C:20](=[O:42])[C:21]1[CH:26]=[C:25]([C:27]2[CH:28]=[N:29][C:30]([C:35]([F:38])([F:37])[F:36])=[CH:31][C:32]=2[C:33]#[N:34])[C:24]([Cl:39])=[CH:23][C:22]=1[O:40][CH3:41]>ClCCCl.N#N>[Cl:39][C:24]1[C:25]([C:27]2[CH:28]=[N:29][C:30]([C:35]([F:38])([F:36])[F:37])=[CH:31][C:32]=2[C:33]#[N:34])=[CH:26][C:21]([C:20]([N:5]([C:4]2[CH:7]=[CH:8][CH:9]=[CH:10][C:3]=2[O:1][CH3:2])[CH3:6])=[O:42])=[C:22]([O:40][CH3:41])[CH:23]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a mixture of 2-methoxyl-N-methylaniline (27.7 mg, 0.2 mmol) and Et3Al (196 μL, 1.9 M in toluene, 0.2 mmol) in 1,2-dichloroethane (1 mL) which was preheated at 50° C. for 10 min under N2 atmosphere, was added 4-chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-benzoic acid methyl ester (50 mg, 0.14 mmol). The mixture was sealed in N2 atmosphere and heated at 80° C. for 16 hrs. Upon cooling to rt, the mixture was quenched with 2 N HCl (5 mL) and diluted with 1,2-dichloroethane. The organic layer was separated and concentrated. The residue was purified via reverse phase preparative LCMS to yield 4-chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-N-(2-methoxy-phenyl)-N-methyl-benzamide 38-1 (4.9 mg). MS [M+H]+475.9; tR=5.91 min (method 3)

Workup

temperatureUpon cooling to rt
customthe mixture was quenched with 2 N HCl (5 mL)
additiondiluted with 1,2-dichloroethane
customThe organic layer was separated
concentrationconcentrated
customThe residue was purified via reverse phase preparative LCMS

Sources & evidence

ORD record: ord-4a10fd1c2c324622bc60bdd2ff742988
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481738B2

Reaction notes

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