tert-Butanol → HCID 178433052, compound

A solution of NaClO2 (2.5 g, 27.5 mmol) and NaH2PO4.H2O (2.3 g, 16.3 mmol) in water (6.1 mL) was added to a solution of 4-formyl-2-methylimidazole (0.30 g, 2.72 mmol), 2-methyl-2-butene (17.0 mL of a 2M solution in THF, 34.0 mmol), tBuOH (2.0 mL), and THF (8.5 mL). The solution was stirred at RT for 3 h. EtOAc (10 mL) was added and the resulting solid was filtered and dried to provide 2-methyl-1H-imidazole-4-carboxylic acid (0.33 g, 97%) as a white solid which was used without further purification. A solution of the above acid (0.035 g, 0.28 mmol) in oxalyl chloride (0.15 mL, 1.67 mmol) was heated under reflux for 1 h and then evaporated to dryness. The residue was stirred with 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.061 g, 0.28 mmol) in CH3CN (3. mL), DMF (1 mL), and DIEA (0.4 mL, 2.3 mmol) at RT overnight. Aqueous Na2CO3 was added, and the solution was extracted with 9:1 CH2Cl2:MeOH. The organic phase was dried (Na2SO4), filtered, and purified by Reverse-Phase HPLC (water:acetonitrile with 0.1% TFA) to provide the title compound (0.010 g, 7%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.15 (br. s., 1H), 7.93 (s, 1H), 7.83 (t, J=1.47 Hz, 1H), 7.49-7.55 (m, 2H), 7.48 (t, J=2.11 Hz, 1H), 7.39 (t, J=7.97 Hz, 1H), 4.55 (d, J=5.59 Hz, 2H), 2.54 (s, 3H). ES-LCMS: m/z 419.3, 421.3 (M+1).

1. filtrationthe resulting solid was filtered
2. customdried

ORD record

ord-a8388d4142f44753981db58d4809de8d

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08304419B2