Triethylamine → (S)-N-(quinuclidin-3-yl)-4-(thiophen-2-yl)benzamide

HRID 2088314

Reaktionsgleichung

Reaktionsgleichung von HRID 2088314
C(N(CC)CC)C.Cl.Cl.[NH2:10][C@H:11]1[CH:16]2[CH2:17][CH2:18][N:13]([CH2:14][CH2:15]2)[CH2:12]1.[S:19]1[CH:23]=[CH:22][CH:21]=[C:20]1[C:24]1[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][CH:25]=1.ON1C2C=CC=CC=2N=N1.C(N=C=NC(C)C)(C)C>CO.O.C(#N)C>[N:13]12[CH2:18][CH2:17][CH:16]([CH2:15][CH2:14]1)[C@H:11]([NH:10][C:28](=[O:29])[C:27]1[CH:31]=[CH:32][C:24]([C:20]3[S:19][CH:23]=[CH:22][CH:21]=3)=[CH:25][CH:26]=1)[CH2:12]2

Komponenten

9

Edukt 5

HCID 8471TriethylamineHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 7364984-(Thiophen-2-yl)benzoic acidHCID 12494973(3S)-1-azabicyclo[2.2.2]octan-3-amine dihydrochloride

Produkt 1

HCID 45381302(S)-N-(quinuclidin-3-yl)-4-(thiophen-2-yl)benzamideAusbeute 13,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

0.5 ml of Acetonitrile, 0.25 ml of water, and Triethylamine (108 uL, 0.78 mmol) was dissolved in a flask charged with (S)-(−)-3-Aminoquinuclidine dihydrochloride (47.8 mg, 0.2 mmol) at room temperature. To the mixture was added 4-(2-Thienyl)benzoic acid (49 mg, 2.4 mmol) and 1-hydroxy benzotriazole (33.8 mg, 0.25 mmol) followed by addition of N,N′-Diisopropyl carbodimide (38.7 uL, 0.25 mmol). The mixture was then stirred overnight at room temperature. About 2 ml of methanol was added to reaction mixture to resolve a clear solution that was subsequently injected into a Preparative HPLC instrument for purification. Desired fractions were combined and concentrated under vacuum. (S)—N-(quinuclidin-3-yl) -4-(thiophen-2-yl)benzamide (8.2 mg, 13% yield) was isolated at an oil. 1H NMR (400 MHz, Methanol-D4) δ (ppm): 7.90 (dt, J=8.7, 1.9 Hz, 2H), 7.76 (dt, J=8.6, 1.9 Hz, 2H), 7.53 (dd, J=3.7, 1.1 Hz, 1H), 7.48 (dd, J=4.0, 1.1 Hz, 1H), 7.14 (dd, J=3.5, 1.6 Hz, 1H), 4.45 (m, 1H), 3.86 (ddd, J=10.0, 3.0, 2.5 Hz, 1H), 3.37 (m, 4H), 2.38 (m, 1H), 2.26 (m, 1H), 2.11 (m, 2H), 1.95 (m, 1H). LCMS (ESI): m/z 313.1 (M+H [C18H20N2OS]=313.13).

Aufarbeitung

  1. customwas subsequently injected into a Preparative HPLC instrument for purification
  2. concentrationconcentrated under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-2e22ae0e8eee48949b12af0aaaf4f503
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08435762B2

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