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

HRID 1486005Notes

Reaction equation

HRID 1486005 reaction equation
[O:1]([C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[NH:5][CH3:6])[CH3:2].CO[C:13](=[O:35])[C:14]1[CH:19]=[C:18]([C:20]2[CH:21]=[N:22][C:23]([C:28]([F:31])([F:30])[F:29])=[CH:24][C:25]=2[C:26]#[N:27])[C:17]([Cl:32])=[CH:16][C:15]=1[O:33][CH3:34]>C1(C)C=CC=CC=1.ClCCCl.N#N>[Cl:32][C:17]1[C:18]([C:20]2[CH:21]=[N:22][C:23]([C:28]([F:31])([F:29])[F:30])=[CH:24][C:25]=2[C:26]#[N:27])=[CH:19][C:14]([C:13]([N:5]([C:4]2[CH:7]=[CH:8][CH:9]=[CH:10][C:3]=2[O:1][CH3:2])[CH3:6])=[O:35])=[C:15]([O:33][CH3:34])[CH:16]=1

Participants

6

Reactant 2

HCID 27595792-Methoxy-N-methylanilineHCID 686025434-Chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-benzoic acid methyl ester

Product 1

HCID 593703324-Chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-N-(2-methoxy-phenyl)-N-methyl-benzamideYield 7.4%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 947NitrogenSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-methoxyl-N-methylaniline (27.7 mg, 0.2 mmol) and Et3AI (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

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

Sources & evidence

ORD record
ord-84052d9a84644dd79001f6e49691e5e0
Source dataset
uspto-grants-2016_08
Patent number
US09422310B2

Reaction notes

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