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2-Chloro-1,4-benzenedicarboxylic acid, 1-methyl ester (Example 1; 84.3 mg, 0.393 mmol) was suspended in dichloromethane (1.5 mL) and the mixture was cooled to 0° C. BOP reagent (191 mg, 0.432 mmol) was added in one portion, followed by 4-aminomethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (Example 12; 91 mg, 0.393 mmol) with a 2×0.25 mL wash of dichloromethane. Duisopropylethylamine (0.21 g, 1.62 mmol) was added over 1 min at ˜0° C. The mixture was stirred at ˜0° C. for 30 min and then at room temperature for 3.5 h. The mixture was concentrated to remove dichloromethane, and ethyl acetate (60 mL) was added. The solution was washed with 1 M HCl , sodium hydrogen carbonate solution, and brine (10 mL each), then dried (MgSO4), filtered, and concentrated. Ethyl acetate/petroleum ether was added and the insoluble material was filtered off to give 2-chloro-4-[[[[1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl]methyl]amino]carbonyl]benzoic acid, methyl ester (93 mg, 55%) as a white solid.

1. washwash of dichloromethane
2. additionDuisopropylethylamine (0.21 g, 1.62 mmol) was added over 1 min at ˜0° C
3. waitat room temperature for 3.5 h
4. concentrationThe mixture was concentrated
5. customto remove dichloromethane, and ethyl acetate (60 mL)
6. additionwas added
7. washThe solution was washed with 1 M HCl , sodium hydrogen carbonate solution, and brine (10 mL each)
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated
11. additionEthyl acetate/petroleum ether was added
12. filtrationthe insoluble material was filtered off