tert-butyl 4-((3-iodo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylate → Tert-butyl 2'-isopropyl-7'-oxo-2',4',6',7'-tetrahydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridine]-1-carboxylate

HRID 880903Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 880903
I[C:2]1[C:6]([CH2:7][C:8]2([N:21]=[C:22]=[O:23])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:5][N:4]([CH:24]([CH3:26])[CH3:25])[N:3]=1.C([Li])(C)(C)C>O1CCCC1>[CH:24]([N:4]1[CH:5]=[C:6]2[C:2]([C:22](=[O:23])[NH:21][C:8]3([CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]3)[CH2:7]2)=[N:3]1)([CH3:26])[CH3:25]

Komponenten

4

Edukt 2

HCID 86664613tert-butyl 4-((3-iodo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylateHCID 178418306HCID 178418306, Verbindung

Produkt 1

HCID 67491432Tert-butyl 2'-isopropyl-7'-oxo-2',4',6',7'-tetrahydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridine]-1-carboxylateAusbeute 63,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a −78° C. solution of tert-butyl 4-((3-iodo-1-isopropyl-1H-pyrazol-4-yl)methyl)-4-isocyanatopiperidine-1-carboxylate (280 mg, 0.59 mmol) in tetrahydrofuran (10 mL) was added t-butyl lithium (0.7 mL, 1.7 M in pentane), dropwise. After stirring for 30 minutes at −78° C. the mixture was warmed to 0° C., quenched with 20 mL saturated aqueous ammonium chloride, and stirred an additional 30 minutes at room temperature. The reaction mixture was diluted with 25 mL water and extracted with ethyl acetate (2×50 mL). The combined organics were dried over sodium sulfate, filtered and concentrated. The residue was then purified by flash chromatography (12-100% ethyl acetate/heptanes, 10 g silica gel) to yield tert-butyl 2′-isopropyl-7′-oxo-2′,4′,6′,7′-tetrahydrospiro[piperidine-4,5′-pyrazolo[3,4-c]pyridine]-1-carboxylate (130 mg) as a colorless solid. +ESI (M+H) 349.1; 1H NMR (500 MHz, CDCl3, δ): 7.28 (s, 1H), 5.78 (s, 1H), 4.57 (spt, J=6.6 Hz, 1H), 3.59 (m, 2H), 3.37 (m, 2H), 2.82 (s, 2H), 1.74 (m, 4H), 1.55 (d, J=6.6 Hz, 6H), 1.47 (s, 9H).

Aufarbeitung

  1. temperaturewas warmed to 0° C.
  2. customquenched with 20 mL saturated aqueous ammonium chloride
  3. stirringstirred an additional 30 minutes at room temperature
  4. additionThe reaction mixture was diluted with 25 mL water
  5. extractionextracted with ethyl acetate (2×50 mL)
  6. dry with materialThe combined organics were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was then purified by flash chromatography (12-100% ethyl acetate/heptanes, 10 g silica gel)

Quellen und Nachweise

ORD-Eintrag
ord-3eb6712ea98f47bead292407497944d9
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08993586B2

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