Reaktion #2161295

Reaktionsgleichung

[5-(4-fluorobenzyl)-3-(1H-imidazol-4-yl)-1H-pyrazol-1-yl]acetic acid

(R)-piperidin-3-ol

EDCI

HOBt

NMM

→

title compound

Ausbeute 15.6%

(3R)-1-{[5-(4-fluorobenzyl)-3-(1H-imidazol-4-yl)-1H-pyrazol-1-yl]acetyl}piperidin-3-ol

Ausbeute 15.6%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe mixture was concentrated in vacuo
2. 2
   workup.ADDITIONthe residue was diluted with water (5 mL)
3. 3
   ExtraktionThe mixture was extracted with CH2Cl2 (3×5 mL)
4. 4
   Waschenwashed with 1 N aq. NaOH (3×10 mL), water (3×5 mL) and brine (25 mL)
5. 5
   Trocknendried over MgSO4
6. 6
   Sonstigeevaporated
7. 7
   SonstigeThe residue was purified via column chromatography (silica gel, EtOAc/Petroleum ether 1:4)
8. 8
   Sonstigeto yield crude material (201.0 mg), which
9. 9
   Sonstigewas further purified via prep

Vorschrift

A mixture of [5-(4-fluorobenzyl)-3-(1H-imidazol-4-yl)-1H-pyrazol-1-yl]acetic acid (0.5 g, 1.67 mmol), (R)-piperidin-3-ol (0.30 g, 2.50 mmol), EDCI (0.58 g, 3.0 mmol), HOBt (0.40 g, 3.0 mmol) and NMM (1.0 mL, 10.0 mmol) in DMF (15 mL) was stirred at room temperature overnight. The mixture was concentrated in vacuo and the residue was diluted with water (5 mL). The mixture was extracted with CH2Cl2 (3×5 mL) and the organics combined, washed with 1 N aq. NaOH (3×10 mL), water (3×5 mL) and brine (25 mL), dried over MgSO4 and evaporated. The residue was purified via column chromatography (silica gel, EtOAc/Petroleum ether 1:4) to yield crude material (201.0 mg), which was further purified via prep. HPLC to yield the title compound (100 mg, 15%) as a white solid. 1H NMR (400 MHz, MeOD): δ ppm 8.837 (s, 1H), 7.699 (s, 1 H), 7.303 (m, 2 H), 7.078 (m, 2 H), 6.337 (s, 1 H), 3.992-3.039 (m, 7 H), 1.994-1.400 (m, 4 H).

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