Tetrahydrofuran → 2-(3-Chloro-4-fluorophenyl)-N5-(1,3-difluoro-2-methylpropan-2-yl)-6,7-dihydropyrazolo[1,5-a]pyrazine-3,5(4H)-dicarboxamide

温度

70 °C

A stirred solution of Intermediate 209B (28.1 mg, 0.204 mmol) in toluene (2 mL) at RT under nitrogen was added TEA (0.043 mL, 0.305 mmol), DPPA (0.047 mL, 0.204 mmol) and the solution was heated at 70° C. and stirred for 2 h. The reaction mass was cooled to RT and to it was added Intermediate 185B (30 mg, 0.102 mmol) in THF (1 mL) was added and the reaction mixture was stirred at RT for 12 h. The reaction mass was diluted with ethyl acetate (25 mL), the organic layer was separated, washed with a 10% aqueous solution of NaHCO3, water, brine dried over Na2SO4, filtered, and the filtrate evaporated. The crude compound was purified by preparative HPLC to afford Compound 209 as pale yellow solid (11 mg, 24% yield). The HPLC Retention times 1.963 min. and 1.968 min. (Methods J and K respectively); MS(ES): m/z=430.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.85 (dd, J=7.31, 2.16 Hz, 1H), 7.64-7.73 (m, 1H), 7.42-7.52 (m, 1H), 7.15-7.30 (m, 2H), 6.62 (s, 1H), 4.73 (s, 2H), 4.64 (s, 2H), 4.52 (s, 2H), 4.14 (s, 2H), 3.84 (s, 2H), 1.31 (t, J=2.07 Hz, 3H).

1. temperatureThe reaction mass was cooled to RT and to it
2. additionwas added
3. stirringthe reaction mixture was stirred at RT for 12 h
4. customthe organic layer was separated
5. washwashed with a 10% aqueous solution of NaHCO3, water, brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. customthe filtrate evaporated
9. customThe crude compound was purified by preparative HPLC

ORDレコード

ord-b536113cd30f49528d6a74eeeca16816

出典データセット

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09273058B2