Reaktion #617035

Reaktionsgleichung

ACN H2O

ACN H2O

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

HCl

→

product

Ausbeute 2.5%

N-(3-(5-chloro-2-(difluoromethoxy)phenyl)-1-((1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

Ausbeute 2.5%

Lösungsmittel

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe resulting mixture was concentrated under vacuum
2. 2
   SonstigeThis resulted in 1.85 g crude product, which
3. 3
   Sonstigewas sufficient for next step without further purification
4. 4
   SonstigeA small portion was purified for characterization and biological submission
5. 5
   SonstigeThe crude product (100 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1)

Vorschrift

To a solution of tert-butyl 4-[4-([3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]methyl)-1H-1,2,3-triazol-1-yl]piperidine-1-carboxylate (1.98 g, 2.96 mmol) in methanol (30 mL) was added concentrated HCl aqueous solution (15 mL). The resulting solution was stirred for 5 h at room temperature. The resulting mixture was concentrated under vacuum. This resulted in 1.85 g crude product, which was sufficient for next step without further purification. A small portion was purified for characterization and biological submission. The crude product (100 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ACN/H2O (10 mmol NH4HCO3)=18% increasing to ACN/H2O (10 mmol NH4HCO3)=49% within 9 min; Detector, UV 254 nm. 42.1 mg product was obtained. This resulted in 42.0 mg of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[[1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl]methyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a light yellow solid. LCMS (Method 36) [M+H]+=569.2, RT=2.59 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.69 (s, 1H), 9.34 (d, 1H, J=6.4 Hz), 8.68-8.64 (m, 2H), 8.40 (s, 1H), 8.22 (s, 1H), 7.67-7.61 (m, 2H), 7.45 (d, 1H, J=8.4 Hz), 7.28 (dd, 1H, J=4.2, 7.0 Hz), 7.06 (t, 1H, J=73.4 Hz), 5.49 (s, 2H), 4.58-4.51 (m, 1H), 3.05-3.02 (m, 2H), 2.62-2.57 (m, 1H), 2.30-2.25 (br, 1H), 2.01-1.98 (m, 2H), 1.87-1.73 (m, 2H).

Quelle