Reaktion #616986

Reaktionsgleichung

[1-[(tert-butoxy)carbonyl]piperidin-4-yl]methyl 1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)piperidine-4-carboxylate

→

piperidin-4-ylmethyl 1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)piperidine-4-carboxylate

Lösungsmittel

HCl dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe resulting mixture was concentrated under vacuum
2. 2
   workup.ADDITIONThe resulting solution was diluted with 10 mL of methanol
3. 3
   EinengenThe resulting mixture was concentrated under vacuum
4. 4
   SonstigeThe crude product was purified by Prep-HPLC with the following conditions (Prep-HPLC-005)
5. 5
   workup.WAITup to 95.0% in 1 min
6. 6
   Sonstigein 1 min
7. 7
   workup.WAITdown to 30.0% in 2 min)

Vorschrift

A solution of [1-[(tert-butoxy)carbonyl]piperidin-4-yl]methyl 1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)piperidine-4-carboxylate (150 mg, 0.19 mmol) and saturated HCl dioxane solution (10 mL) was stirred at room temperature overnight. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 10 mL of methanol. The resulting mixture was concentrated under vacuum. The crude product was purified by Prep-HPLC with the following conditions (Prep-HPLC-005): Column, XBridge Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, water with 0.05% FA and MeCN (30.0% up to 33.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 30.0% in 2 min); Detector, UV 254/220 nm. This resulted in 82.3 mg (59%) of the formic acid salt of piperidin-4-ylmethyl 1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)piperidine-4-carboxylate as a light yellow solid. LCMS (Method 20) [M+H]+=671.3, RT=1.58 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.76 (s, 1H), 9.33 (dd, 1H, J=1.2, 6.9 Hz), 8.68-8.67 (m, 2H), 8.31 (s, 1H), 7.62 (dd, 1H, J=2.7, 8.7 Hz), 7.55 (d, 1H, J=2.7 Hz), 7.45 (d, 1H, J=8.7 Hz), 7.28 (dd, 1H, J=4.5, 7.2 Hz), 7.01 (t, 1H, J=73.5), 5.25-5.23 (m, 2H), 4.24-4.19 (m, 1H), 3.93-3.85 (m, 3H), 2.83-2.80 (m, 1H), 2.72-2.64 (m, 3H), 1.92-1.87 (m, 3H), 1.71-1.67 (m, 3H), 1.59-1.48 (m, 1H), 1.44-1.23 (m, 2H).

Quelle