Pentafluoroiodobenzene → N-Cyclopropylmethyl-2-ethyl-7-iodo-N-(tetrahydro-2H-pyran-4-ylmethyl)pyrazolo[1,5-a]pyridine-3-amine

HRID 2253397

Reaktionsgleichung

Reaktionsgleichung von HRID 2253397
[CH:1]1([CH2:4][N:5]([C:13]2[C:14]([CH2:22][CH3:23])=[N:15][N:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=23)[CH2:6][CH:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)[CH2:3][CH2:2]1.FC1C([I:31])=C(F)C(F)=C(F)C=1F.O.C1COCC1>O1CCCC1>[CH:1]1([CH2:4][N:5]([C:13]2[C:14]([CH2:22][CH3:23])=[N:15][N:16]3[C:21]([I:31])=[CH:20][CH:19]=[CH:18][C:17]=23)[CH2:6][CH:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)[CH2:3][CH2:2]1

Komponenten

5

Edukt 3

HCID 70008PentafluoroiodobenzeneHCID 21881883Oxolane--water (1/1)HCID 58801672N-Cyclopropylmethyl-N-(2-ethylpyrazolo[1,5-a]pyridin-3-yl)-N-tetrahydro-2H-4-pyranylmethylamine

Produkt 1

HCID 11339625N-Cyclopropylmethyl-2-ethyl-7-iodo-N-(tetrahydro-2H-pyran-4-ylmethyl)pyrazolo[1,5-a]pyridine-3-amineAusbeute 87,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of N-cyclopropylmethyl-N-(2-ethylpyrazolo[1,5-a]pyridin-3-yl)-N-tetrahydro-2H-4-pyranylmethylamine (180 g, 574 mmol) in tetrahydrofuran (1620 mL) was cooled with dry ice-ethanol bath. A 1.6M n-butyllithium-hexane solution (538 mL, 854 mmol) was added dropwise to the solution at an internal temperature of from −73° C. to −64.5° C. After stirring the reaction mixture for 1 hour at the same temperature, pentafluoroiodobenzene (115 mL, 861 mmol) was added dropwise. The reaction mixture was additionally stirred for 1 hour and 20 minutes, and then water/THF (1/1, v/v, 360 mL) was added thereto. Cooling was terminated, and then water (3600 mL) and heptane (3600 mL) were added to the reaction mixture, the aqueous layer was removed and the organic extract was washed with water (3600 mL). A 5N aqueous hydrochloric acid solution (1800 mL) was then added to the organic layer and the aqueous layer was separated off. After cooling the aqueous layer in an ice bath and adding a 5N aqueous sodium hydroxide solution (1620 mL), toluene (3600 mL) was further added to the reaction mixture and the organic layer was separated off. The aqueous layer was extracted with toluene (3600 mL), and both organic extracts were combined and concentrated to afford 220 g of the title compound as a dark green oil (87.3% yield)

Aufarbeitung

  1. additionA 1.6M n-butyllithium-hexane solution (538 mL, 854 mmol) was added dropwise to the solution at an internal temperature of from −73° C. to −64.5° C
  2. additionwas added dropwise
  3. temperatureCooling
  4. customwas terminated
  5. additionwater (3600 mL) and heptane (3600 mL) were added to the reaction mixture
  6. customthe aqueous layer was removed
  7. extractionthe organic extract
  8. washwas washed with water (3600 mL)
  9. additionA 5N aqueous hydrochloric acid solution (1800 mL) was then added to the organic layer
  10. customthe aqueous layer was separated off
  11. temperatureAfter cooling the aqueous layer in an ice bath
  12. additionadding a 5N aqueous sodium hydroxide solution (1620 mL), toluene (3600 mL)
  13. additionwas further added to the reaction mixture
  14. customthe organic layer was separated off
  15. extractionThe aqueous layer was extracted with toluene (3600 mL)
  16. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-f950e6a68cf54f0c96ee0327f0202171
Quelldatensatz
uspto-grants-2008_01
Patentnummer
US07323569B2

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