Acetic Acid → 4-(2-chloro-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

温度

-78 °C

A sealable vial was charged with 4-aminopyrimidine (0.101 g, 1.067 mmol) sealed with a septa cap and placed under an N2 atmosphere. THF (2 mL) was added and the solution was cooled to −78° C. Lithium bis(trimethylsilyl)amide, 1.0 M in THF (1.067 mL, 1.067 mmol) was added dropwise and the solution was maintained at −78° C. for 15 min. Perfluorophenyl 4-(2-chloro-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (INTERMEDIATE F, 0.543 g, 0.970 mmol) was added as a solution in THF (3 mL) and the solution was allowed to warm to rt, and the mixture was stirred for 40 min. To the solution was added acetic acid (0.2 mL) to provide a bright yellow/orange mixture. The mixture was concentrated to dryness. The residue was absorbed onto a plug of silica gel and purified by chromatography through a silica gel column (40 g), eluting with a gradient of 10% to 100% EtOAc in heptane, to provide 4-(2-chloro-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.050 g, 0.106 mmol) as tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.60-3.84 (m, 2 H) 4.24-4.48 (m, 2 H) 6.32 (d, J=8.51 Hz, 1 H) 6.98-7.05 (m, 1 H) 7.24-7.31 (m, 1 H) 7.34 (s, 1 H) 7.71-7.79 (m, 1 H) 7.82-7.89 (m, 1 H) 8.03-8.11 (m, 1 H) 8.31-8.43 (m, 1 H) 8.56-8.75 (m, 1 H). m/z (ESI) 471.0 (M+H)+.

1. customsealed with
2. customa septa cap
3. temperaturethe solution was maintained at −78° C. for 15 min
4. temperatureto warm to rt
5. customto provide a bright yellow/orange mixture
6. concentrationThe mixture was concentrated to dryness
7. customThe residue was absorbed onto a plug of silica gel
8. custompurified by chromatography through a silica gel column (40 g)
9. washeluting with a gradient of 10% to 100% EtOAc in heptane

ORDレコード

ord-fbc86ddd58164b8488313d48fa3e9d18

出典データセット

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09346798B2