Water → HCID 349055, compound

Temperature

0 °C

To a solution of N-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-(trifluoromethyl)-phenyl]-7-({2-[(cyclopropylcarbonyl)amino]pyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxamide (0.250 g, 0.39 mol) in THF (5 mL) at 0° C. was added 1.0 M tetra-n-butylammonium fluoride in THF (0.43 mL). The reaction mixture was allowed to stir at 0° C. for 1 h and then at rt overnight. Water was added and the reaction mixture was extracted with EtOAc. The organic solutions were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give 7-({2-[(cyclopropylcarbonyl)amino]pyridin-4-yl}-oxy)-N-3(hydroxymethyl)-5-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydronaphthalene-2-carboxamide I-206 (199 mg, 88%) as a white solid. 1H NMR (400 MHz, d6-DMSO, HCl salt) δ: 11.48 (br s, 1H), 10.46 (s, 1H), 8.21 (d, 1H), 8.02 (s, 1H), 7.79 (s, 1H), 7.35 (br s, 1H), 7.31 (s, 1H), 7.22 (d, 1H), 6.93-7.02 (m, 2H), 6.81-6.86 (m, 1H), 4.54 (s, 2H), 2.76-2.97 (m, 5H), 2.07-2.15 (m, 1H), 1.90-1.98 (m, 1H), 1.73-1.85 (m, 1H), and 0.81-0.89 (m, 4H). LCMS: (FA) ES+526.4, ES−524.5.

1. customat rt
2. customovernight
3. extractionthe reaction mixture was extracted with EtOAc
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by column chromatography

ORD record

ord-7af6f92e8e104158bf7086ab8fb2fba7

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08110687B2