Sodium Iodide → 3-[6-(Azetidine-1-carbonyl)pyridin-3-yl]oxy-5-(1-cyclobutyl-2-oxo-pyrrolidin-3-yl)oxy-N-(5-methylpyrazin-2-yl)benzamide

HRID 600519Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 600519
[N:1]1([C:5]([C:7]2[N:12]=[CH:11][C:10]([O:13][C:14]3[CH:15]=[C:16]([CH:31]=[C:32]([C:34](=[O:43])[NH:35][C:36]4[CH:41]=[N:40][C:39]([CH3:42])=[CH:38][N:37]=4)[CH:33]=3)[O:17][CH:18]([CH2:24][CH2:25]OS(C)(=O)=O)[C:19]([O:21]CC)=O)=[CH:9][CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.[I-].[Na+].[CH:46]1([NH2:50])[CH2:49][CH2:48][CH2:47]1>C(#N)C>[N:1]1([C:5]([C:7]2[N:12]=[CH:11][C:10]([O:13][C:14]3[CH:33]=[C:32]([CH:31]=[C:16]([O:17][CH:18]4[CH2:24][CH2:25][N:50]([CH:46]5[CH2:49][CH2:48][CH2:47]5)[C:19]4=[O:21])[CH:15]=3)[C:34]([NH:35][C:36]3[CH:41]=[N:40][C:39]([CH3:42])=[CH:38][N:37]=3)=[O:43])=[CH:9][CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1

Komponenten

5

Edukt 3

HCID 5238Sodium IodideHCID 75645CyclobutylamineHCID 86621533Ethyl 2-[3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]-4-methylsulfonyloxy-butanoate2×

Produkt 1

HCID 249530143-[6-(Azetidine-1-carbonyl)pyridin-3-yl]oxy-5-(1-cyclobutyl-2-oxo-pyrrolidin-3-yl)oxy-N-(5-methylpyrazin-2-yl)benzamideAusbeute 43 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a solution of ethyl 2-[3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]-4-methylsulfonyloxy-butanoate (Intermediate 27) (250 mg, 0.41 mmol) in acetonitrile (5 mL), was added sodium iodide (62 mg, 0.41 mmol) and cyclobutylamine (70 μL, 0.81 mmol). The resulting mixture was heated in a microwave at 120° C. for 60 minutes. The solvent was evaporated under reduced pressure and the residue purified by flash chromatography eluting with 0-40% methanol in DCM to afford the product (95 mg, 43%). 1H NMR δ (300 MHz, CDCl3) 1.69-1.78 (2H, m), 2.13-2.23 (5H, m), 2.30-2.40 (2H, m), 2.55-2.64 (4H, m), 3.39-3.47 (1H, m), 3.57-3.64 (1H, m), 4.24 (2H t), 4.62-4.72 (3H, m), 4.91-4.96 (1H, m), 6.96 (1H, t), 7.22 (1H t), 7.36-7.40 (1H, m), 7.45 (1H, t), 8.09-8.13 (2H, m), 8.32 (1H, d), 8.61 (1H, s), 9.51 (1H, d); m/z 543 (M+H)+.

Aufarbeitung

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue purified by flash chromatography
  3. washeluting with 0-40% methanol in DCM

Quellen und Nachweise

ORD-Eintrag
ord-1af5cc8cc7c148cc81e3e8743dffcf80
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902200B2

Notizen zur Reaktion

Wird geladen…