Triethylamine → tert-Butyl 4-(3-methoxy-4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

温度

30 °C

tert-Butyl 4-(3-methoxy-4-((4-((2-(2-methoxy-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I28) (5.52 g, 8.84 mmol) was dissolved in DMF (250 mL) then triethylamine (1 mL) and Pd/C (2.50 g) were added and the mixture stirred at 30° C. under hydrogen. After 16 hours the mixture was filtered through celite and the celite washed with DMF (250 mL). Triethylamine (1 mL) and Pd/C (2.50 g) were added to the combined filtrates and the mixture stirred at 30° C. under hydrogen. After 18 hours the resulting mixture was filtered through celite washing with ethyl acetate (300 mL). The filtrate was divided into two lots; each was poured into water (800 mL) and the resulting mixture extracted with ethyl acetate (3×300 mL). The ethyl acetate extracts from each lot were combined, washed with water (2×500 mL) and brine, dried (sodium sulfate) and evaporated. The two workups were combined and chromatographed (120 g silica cartridge, 0-20% ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I21) (3.620 g, 65% yield) as a white solid; 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 8.37 (d, J=8.3 Hz, 1H), 7.91 (s, 1H), 7.29-7.18 (m, overlaps with CHCl3), 6.85 (dd, J=8.3, 1.8 Hz, 1H), 6.77 (d, J=1.8 Hz, 1H), 4.26 (s, 2H), 3.93 (s, 3H), 3.68 (s, 3H), 3.19-3.01 (m, 4H), 2.81 (t, J=12.7 Hz, 2H), 2.64 (tt, J=12.0, 3.5 Hz, 1H), 1.85 (d, J=13.3 Hz, 2H), 1.70-1.57 (m, overlaps with water), 1.49 (s, 9H). LCMS Method C: rt 7.14 min; m/z 629.2 [M+H]+, 573.1 [M-tBu+2H]+; m/z 627.2 [M−H].

1. filtrationAfter 16 hours the mixture was filtered through celite
2. washthe celite washed with DMF (250 mL)
3. additionTriethylamine (1 mL) and Pd/C (2.50 g) were added to the combined filtrates
4. stirringthe mixture stirred at 30° C. under hydrogen
5. filtrationAfter 18 hours the resulting mixture was filtered
6. washthrough celite washing with ethyl acetate (300 mL)
7. additioneach was poured into water (800 mL)
8. extractionthe resulting mixture extracted with ethyl acetate (3×300 mL)
9. washwashed with water (2×500 mL) and brine
10. dry with materialdried (sodium sulfate)
11. customevaporated
12. customchromatographed (120 g silica cartridge, 0-20% ethyl acetate/petroleum benzine 40-60° C.)

ORDレコード

ord-aabf81af334547349f9286f78818e1ba

出典データセット

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09120761B2