Reaction SMILES: [NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[C:6]([O:12][CH3:13])[C:3]=1[C:4]#[N:5].CS(O)(=O)=[O:16].ClCCl.Cl>O>[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[C:6]([O:12][CH3:13])[C:3]=1[C:4]([NH2:5])=[O:16]
Reactant: COc1cc(N)c(C#N)c(OC)c1
Reactant: CS(=O)(=O)O
Agent: Cl
Solvent: ClCCl
Solvent: O
Product: COc1cc(N)c(C(N)=O)c(OC)c1
Temperature: 107.5 °C
Reaction time: 1 h
Yield: 75.9 %

Procedure:
2-amino-4,6-dimethoxybenzonitrile (10.0 g, 0.056 mol, 1 eq.) was charged to a 1-L glass vessel under N2 atmosphere and agitation was started. Methanesulfonic acid (120 mL, 1.848 mol, 33 eq.) was charged to the vessel and the reaction was heated at 100-115° C. for 1-2 hours. Upon verification of reaction completion by HPLC, the batch was cooled to 20-30° C. Upon cooling, dichloromethane (67 mL) and cool water (164 mL) (5-10° C.) were added to keep the temperature in the range of 10-30° C. 50% caustic (94 mL) was charged to the vessel using an addition funnel while maintaining 0-30° C. Fine pH adjustment to 6.5 to 7.3 was completed using either 32% HCl or 50% caustic. Upon equilibration, the first organic phase cut was performed. The aqueous layer was extracted two additional times with DCM (74 mL and 57 mL respectively). Dichloromethane (54 mL) was added to the combined organic layers and the organic layer was washed with water (143 mL) to remove methanesulfonate salts. Dichloromethane (16 mL) was added to the combined organic layers and the organic layer was washed once more with water (143 mL) to remove methanesulfonate salts. The batch was distilled using (5-10 inches Hg) vacuum to a pot volume of 4.5 volumes DCM (45 mL). The contents of the vessel were stirred for 1 hour at 38° C. The vessel was cooled to 23-28° C. over 1 hour with slow agitation. When clouding was observed, the vessel was slowly charged with 14.4 volumes MtBE (144 mL) and the batch was agitated for 30 min at 25° C. (ratio of DCM/MtBE is 1:3.2; total volumes of solvent is 18.9). The batch was slowly cooled to between −5° C. and 5° C. over at least 3 hours. The batch was held for at least 1 hour between −5° C. and 0° C. Precipitation was verified through collection of at least two samples from the liquor to determine the amount of 2-amino-4,6-dimethoxybenzamide remaining in solution. The batch was isolated by filtration and the wet cake washed with a cold (0° C.) mixture of 1:4 DCM/MtBE (51 mL). The 2-amino-4,6-dimethoxybenzamide wet cake was dried in a vacuum oven (40-45° C., 25 inches Hg) to give 2-amino-4,6-dimethoxybenzamide (8.33 g, 0.0425 mol, 75.7% yield; 53% yield over 5 steps from 3,5-dimethoxyaniline). Use of an alternate solvent to dichloromethane has been studied and performs in a similar fashion to dichloromethane. Examples of alternate solvents include, but are not limited to esters like isopropyl acetate and ethyl acetate, and ethers like 2-methyltetrahydrofuran. In addition, alternate precipitation systems with or without anti-solvent have also been examined. The precipitation system may include, but is not limited to esters like isopropyl acetate, ethers like 2-methyltetrahydrofuran, and alcohols like isopropyl alcohol. The yield range from these modifications in the experimental procedure is 72-79%. In addition, purity of the desired compound is consistently over 99%.