反応 #2358593

反応方程式

water

CH3CN

CH3CN

tert-butyl methyl(2-(methyl((3-(1-(3-methylbutanoyl)piperidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)methyl)amino)ethyl)carbamate

→

3-methyl-1-(4-(4-((methyl (2-(methylamino)ethyl)amino)methyl)-1H-p yrazol-3-yl)piperidin-1-yl)butan-1-one

収率 25.1%

溶媒

ethanol

1,4-dioxane

hydrochloric acid

反応条件

後処理

1. 1
   濃縮The resulting mixture was concentrated under vacuum
2. 2
   その他the residue was purified by Pre-HPLC with the following conditions (1#-Pre-HPLC-005 (Waters))
3. 3
   workup.WAITdown to 18% in 2 min)

実験手順

A solution of tert-butyl methyl(2-(methyl((3-(1-(3-methylbutanoyl)piperidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)methyl)amino)ethyl)carbamate (110 mg, 0.21 mmol, 1.00 equiv) in ethanol (2 mL), 1,4-dioxane (4 mL) and 12N hydrochloric acid (2 mL) was stirred at room temperature overnight. The resulting mixture was concentrated under vacuum and the residue was purified by Pre-HPLC with the following conditions (1#-Pre-HPLC-005 (Waters)): Column, XBridge Shield RP18 OBD Column, 5 μm, 19×150 mm; mobile phase, water with 10 mmol NH4HCO3 and CH3CN (18% CH3CN up to 58% in 10 min, up to 95% in 1 min, down to 18% in 2 min); Detector, UV 254/220 nm to give 17.7 mg (25%) of 3-methyl-1-(4-(4-((methyl (2-(methylamino)ethyl)amino)methyl)-1H-p yrazol-3-yl)piperidin-1-yl)butan-1-one as a colorless solid. 1H-NMR (300 MHz, D2O): δ 7.53 (s, 1H), 4.50-4.40 (m, 1H), 4.10-4.00 (m, 1H), 3.44 (s, 2H), 3.25-3.10 (m, 1H), 3.09-2.95 (m, 1H), 2.80-2.65 (m, 3H), 2.53-2.43 (m, 2H), 2.40-2.20 (m, 5H), 2.13 (s, 3H), 2.00-1.75 (m, 3H), 1.72-1.43 (m, 2H), 0.88 (d, J=6.8 Hz, 6H) ppm. LCMS (method R, ESI): RT=1.26 min, m/z=336.2 [M+H]+.

出典