Iodine → 4-chloro-3-cyano-5-methyl-N-[(3S,4R)-3-(prop-2-en-1-yloxy)piperidin-4-yl]-1H-pyrrole-2-carboxamide

HRID 655759Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 655759
[Cl:1][C:2]1[C:3]([C:26]#[N:27])=[C:4]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][N:14](C(OCC)=O)[CH2:13][C@@H:12]2[O:22][CH2:23][CH:24]=[CH2:25])=[O:9])[NH:5][C:6]=1[CH3:7].II.C[Si](C)(C)[Si](C)(C)C.S([O-])([O-])(=O)=S.[Na+].[Na+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:3]([C:26]#[N:27])=[C:4]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][NH:14][CH2:13][C@@H:12]2[O:22][CH2:23][CH:24]=[CH2:25])=[O:9])[NH:5][C:6]=1[CH3:7]

Komponenten

6

Edukt 4

HCID 807IodineHCID 24477Sodium ThiosulfateHCID 74057HexamethyldisilaneHCID 59402444Ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate2×

Produkt 1

HCID 594025964-chloro-3-cyano-5-methyl-N-[(3S,4R)-3-(prop-2-en-1-yloxy)piperidin-4-yl]-1H-pyrrole-2-carboxamideAusbeute 33,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Versuchsvorschrift

To as solution of ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate (Intermediate 21, 1.1 g, 2.79 mmol) in toluene (190 mL) was added iodine (2.9 g, 11.16 mmol) followed by hexamethyldisilane (4.65 mL, 22.33 mmol). The reaction mixture was heated to reflux for 30 h and then cooled to room temperature. The reaction mixture was treated 10% sodium thiosulphate (150 mL) and the layers were separated. The aqueous layer was extracted with toluene and the organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. Purification by column chromatography (silica, 4% methanol in dichloromethane) afforded 300 mg (33%) of 4-chloro-3-cyano-5-methyl-N-[(3S,4R)-3-(prop-2-en-1-yloxy)piperidin-4-yl]-1H-pyrrole-2-carboxamide

Aufarbeitung

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 30 h
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with toluene
  5. dry with materialthe organic layer was dried over anhydrous sodium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customPurification by column chromatography (silica, 4% methanol in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-51c0382585ff426ead7be86c68e881f1
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08071605B2

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