Diisopropylethylamine → 4-(4-{3-[(2R,5S)-2,5-dimethylpyrrolidin-1-yl]propoxy}-phenyl)-tetrahydro-2H-pyran-4-carbonitrile

온도

160 °C

A (1:3) mixture of 1-[4-(3-bromo-propoxy)-phenyl]-cyclohexanecarbonitrile and 1-[4-(3-chloro-propoxy)-phenyl]-cyclohexanecarbonitrile (150 mg, 0.54 mmol), N,N-diisopropylethylamine (187 μL, 1.07 mmol) and (2R,5S)-2,5-dimethylpyrrolidine (145 mg, 1.07 mmol) in NMP (0.5 mL) was heated at 160° C. in the microwave (Smith Personal Synthesiser) for 400 seconds then 170° C. for 600 seconds. The reaction mixture was quenched with NaHCO3 (15 mL) and extracted with ethyl acetate (2×15 mL), dried over Na2SO4, filtered and concentrated in vacuo. The compound was purified by column chromatography on Biotage® silica gel, eluting with dichloromethane:methanol:ammonia, 97:3:0.3 to 90:10:1. Yield=28% 1H NMR (400 MHz, CDCl3) δ7.36 (d, 2H), 6.92 (d, 2H), 4.10-4.04 (m, 2H), 4.00 (t, 2H), 3.88 (dt, 2H), 2.72 (t, 2H), 2.64-2.52 (m, 2H), 2.14-1.98 (m, 4H), 1.94 (pentet, 2H), 1.86-1.78 (m, 2H), 1.42-1.28 (m, 2H), 1.10 (d, 6H); HRMS (ESI+) 343.2380 (M+H)+.

1. customThe reaction mixture was quenched with NaHCO3 (15 mL)
2. extractionextracted with ethyl acetate (2×15 mL)
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe compound was purified by column chromatography on Biotage® silica gel
7. washeluting with dichloromethane

ORD 기록

ord-c53349d7cebb48d5a8beae03db991b2f

출처 데이터셋

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07456164B2