Trimethylaluminum → N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]benzamide

온도

60 °C

A 2M solution of trimethylaluminium in toluene (1.875 mL, 3.75 mmol) was added dropwise to a stirred suspension of ethyl 4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzoate (0.394 g, 1.50 mmol) and 5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-amine (0.374 g, 1.5 mmol) in toluene (10 mL) at 20° C., over a period of 5 mins under nitrogen. The resulting solution was stirred at 60° C. for 5 h. The reaction mixture was cooled and the reaction quenched by diluting with acetone (100 ml) and excess damp sodium sulphite added in portions. This was stirred for 60 mins. The resulting solid filtered off, washed with 10% methanol in DCM. The filtrate was evaporated to give crude product. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 5% 2M ammonia/MeOH in DCM. Pure fractions were evaporated to dryness to afford the title compound (0.287 g, 41.1%) as a white solid. 1H NMR (500.13 MHz, DMSO-d6) δ 1.08 (6H, d), 2.31 (2H, t), 3.70-3.73 (2H, m), 3.78 (6H, s), 5.10 (2H, s), 5.64 (1H, s), 6.46 (1H, t), 6.62 (2H, d), 6.95-6.97 (2H, m), 7.83-7.85 (2H, m), 10.21 (1H, s), 11.09 (1H, s). MS: m/z 466 (MH+).

1. temperatureThe reaction mixture was cooled
2. customthe reaction quenched
3. additionby diluting with acetone (100 ml) and excess damp sodium sulphite
4. additionadded in portions
5. stirringThis was stirred for 60 mins
6. filtrationThe resulting solid filtered off
7. washwashed with 10% methanol in DCM
8. customThe filtrate was evaporated
9. customto give crude product
10. customThe crude product was purified by silica column chromatography
11. washeluting with a gradient of 0 to 5% 2M ammonia/MeOH in DCM
12. customPure fractions were evaporated to dryness

ORD 기록

ord-d94abdb39b3743fba066ea0ec35ed9e8

출처 데이터셋

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08604022B2