Acetic Acid → [1-(3,5-Diethoxy-4-fluoro-benzyl)-piperidin-4-yl]-(5-methanesulfonyl-pyridin-2-yl)-amine

HRID 913159Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 913159
[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([NH:11][CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[N:9][CH:10]=1)(=[O:4])=[O:3].[CH2:18]([O:20][C:21]1[CH:22]=[C:23]([CH:26]=[C:27]([O:30][CH2:31][CH3:32])[C:28]=1[F:29])[CH:24]=O)[CH3:19].C(N(C(C)C)C(C)C)C.C(O)(=O)C.C([BH3-])#N.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.O>[CH2:18]([O:20][C:21]1[CH:22]=[C:23]([CH:26]=[C:27]([O:30][CH2:31][CH3:32])[C:28]=1[F:29])[CH2:24][N:15]1[CH2:16][CH2:17][CH:12]([NH:11][C:8]2[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:10][N:9]=2)[CH2:13][CH2:14]1)[CH3:19]

Komponenten

9

Edukt 6

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 591282733,5-Diethoxy-4-fluoro-benzaldehyde2×HCID 59383087(5-Methanesulfonyl-pyridin-2-yl)-piperidin-4-yl-amine

Produkt 1

HCID 67400612[1-(3,5-Diethoxy-4-fluoro-benzyl)-piperidin-4-yl]-(5-methanesulfonyl-pyridin-2-yl)-amineAusbeute 71 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of (5-methanesulfonyl-pyridin-2-yl)-piperidin-4-yl-amine (0.12 g, 0.5 mmol, 1.0 equiv; intermediate B16) and 3,5-diethoxy-4-fluoro-benzaldehyde (0.11 g, 0.5 mmol, 1.0 equiv; intermediate E5) in ethanol (5 mL) under an atmosphere of Ar was added N-ethyl diisopropylamine (0.19 mL, 0.15 g, 1.2 mmol, 2.3 equiv) and glacial acetic acid (0.05 mL, 0.06 g, 1.0 mmol, 2.0 equiv) and the mixture heated to 50° C. for 2 h. After cooling down to 35° C., sodium cyanoborohydride (0.16 g, 2.5 mmol, 5.1 equiv) was added and the reaction mixture heated again to 50° C. for 1.5 h. It was then poured into crashed ice, the pH of the water phase adjusted to ˜10 by addition of a sat. solution of sodium carbonate and the mixture extracted twice with dichloromethane. The combined organic phases were washed with water, dried over MgSO4, filtered and concentrated by evaporation under reduced pressure. The crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol to give 0.16 g (71%) of the title compound as colorless foam. MS (ISP): 452.1 [M+H]+.

Aufarbeitung

  1. temperatureAfter cooling down to 35° C.
  2. temperaturethe reaction mixture heated again to 50° C. for 1.5 h
  3. additionIt was then poured
  4. extractionthe mixture extracted twice with dichloromethane
  5. washThe combined organic phases were washed with water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated by evaporation under reduced pressure
  9. customThe crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol

Quellen und Nachweise

ORD-Eintrag
ord-48a351038ba5403e9a887f040ad0d7e3
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08026255B2

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