Tetrahydrofuran → (2S)-2-[(4-{[5-(methoxymethyl)furan-3-yl]ethynyl}benzoyl)(methyl)amino]-N,2-dimethyl-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamide

HRID 1519718Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1519718
C1COCC1.[C:6]([C:8]1[CH:9]=[C:10]([CH2:13][O:14][CH3:15])[O:11][CH:12]=1)#[CH:7].I[C:17]1[CH:42]=[CH:41][C:20]([C:21]([N:23]([CH3:40])[C@:24]([CH3:39])([C:29]([NH:31][O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)=[O:30])[C:25]([NH:27][CH3:28])=[O:26])=[O:22])=[CH:19][CH:18]=1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C(OCC)(=O)C>[CH3:15][O:14][CH2:13][C:10]1[O:11][CH:12]=[C:8]([C:6]#[C:7][C:17]2[CH:42]=[CH:41][C:20]([C:21]([N:23]([CH3:40])[C@:24]([CH3:39])([C:29]([NH:31][O:32][CH:33]3[CH2:38][CH2:37][CH2:36][CH2:35][O:34]3)=[O:30])[C:25]([NH:27][CH3:28])=[O:26])=[O:22])=[CH:19][CH:18]=2)[CH:9]=1

Komponenten

7

Edukt 3

HCID 8028TetrahydrofuranHCID 86679252HCID 86679252, Verbindung2×HCID 866792824-Ethynyl-2-(methoxymethyl)furan

Produkt 1

HCID 86679283(2S)-2-[(4-{[5-(methoxymethyl)furan-3-yl]ethynyl}benzoyl)(methyl)amino]-N,2-dimethyl-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamideAusbeute 84 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

PdCl2(PPh3)2 (70 mg), CuI (38 mg) and TEA (1.5 mL) were added to a THF (7.0 mL) solution of 4-ethynyl-2-(methoxymethyl)furan (0.24 g) as obtained in Example 18-(3) and (2S)-2-[(4-iodobenzoyl)(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (Intermediate 15, 0.51 g), and the mixture was stirred for 5.5 hours at room temperature in a nitrogen atmosphere. Ethyl acetate (30 mL), OH type silica gel (1.9 g), cellpure (0.95 g) and activated carbon (50 mg) were added, the insolubles were filtered out, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (gradient elution with ethyl acetate/hexane=75/25→100/0, followed by gradient elution with chloroform/acetone=100/0→70/30) to obtain (2S)-2-[(4-{[5-(methoxymethyl)furan-3-yl]ethynyl}benzoyl)(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (yellow solid) (0.43 g, 84%).

Aufarbeitung

  1. filtrationthe insolubles were filtered out
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe resulting residue was purified by OH type silica gel column chromatography (gradient elution with ethyl acetate/hexane=75/25→100/0, followed by gradient elution with chloroform/acetone=100/0→70/30)

Quellen und Nachweise

ORD-Eintrag
ord-06cdd491e6b641c58d58f2082a162019
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073821B2

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