1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2,5-dioxopyrrolidin-1-yl 5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylate

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Reaction Steps

5-(2,4-Difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylic acid (39.5 g, 113.9 mmol), N-hydroxysuccinimide (17.0 g, 148 mmol) and EDCI (26.0 g, 137 mmol) were dissolved in CH2Cl2 (200 mL). The solution was stirred for 3 hours and then was diluted with 100 mL CH2Cl2 and washed sequentially with a saturated NH4Cl solution, twice with a saturated Na2CO3 solution, and once with brine. The organics were dried (MgSO4), filtered, and concentrated under reduced pressure. The crude residue was precipitated from Et2O to afford 41.0 g of 5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylic acid 2,5-dioxopyrrolidin-1-yl ester (81% yield). 1H NMR (400 MHz, CDCl3) δ 8.26 (s, 1H), 7.95 (s, 1H), 7.20 (s, 1H), 7.05-6.94 (m, 2H), 6.88-6.81 (m, 1H), 4.24 (d, J=7.83 Hz, 2H), 2.90 (s, 4H), 2.43-2.32 (m, 1H), 0.96 (d, J=7.04 Hz, 6H).

Provenance & Evidence