Triethylamine → 1-{1-[3-(4-Fluorophenyl)-propyl]-piperidin-3-ylmethyl}-3-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-urea

HRID 896524Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 896524
Cl.[CH3:2][N:3]1[C:7]([C:8]2[CH:9]=[C:10]([NH:14][C:15]([NH:17][CH2:18][CH:19]3[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]3)=[O:16])[CH:11]=[CH:12][CH:13]=2)=[N:6][N:5]=[N:4]1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][CH:34]=O)=[CH:28][CH:27]=1.C(N(CC)CC)C.C([BH3-])#N>CO.C1(C)C=CC=CC=1>[F:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][CH2:34][N:21]2[CH2:22][CH2:23][CH2:24][CH:19]([CH2:18][NH:17][C:15]([NH:14][C:10]3[CH:11]=[CH:12][CH:13]=[C:8]([C:7]4[N:3]([CH3:2])[N:4]=[N:5][N:6]=4)[CH:9]=3)=[O:16])[CH2:20]2)=[CH:28][CH:27]=1

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 498716Cyano-borohydrideHCID 101977823-(4-Fluorophenyl)propanalHCID 223502531-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-piperidin-3-ylmethylurea hydrochloride

Produkt 1

HCID 99812621-{1-[3-(4-Fluorophenyl)-propyl]-piperidin-3-ylmethyl}-3-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-ureaAusbeute 64,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 1140TolueneLösungsmittel

Versuchsvorschrift

A mixture of 1-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-piperidin-3-ylmethylurea hydrochloride (35 mg, 100 μmol), 3-(4-fluorophenyl)-propionaldehyde (15 mg, 100 μmol), triethylamine (15 μL, 110 μmol), resin-bound cyanoborohydride (prepared according to Ley, S. V., et al., J. Chem. Soc. Perkin Trans. 1, 1998, 2239; 100 mg), toluene (1 mL) and methanol (1 mL) was agitated gently at room temperature for 65 hours. The mixture was filtered, the resin was washed with dichloromethane, and the filtrates were concentrated. The residue was purified by flash chromatography, eluting with 4% methanol in dichloromethane containing 0.4% aqueous ammonium hydroxide, to provide an amorphous white solid (29 mg, 64%). 1H NMR (300 MHz, CDCl3) δ7.88 (s, 1H), 7.79 (d, J=8 Hz, 1H), 7.44 (t, J=8 Hz, 1H), 7.27 (m, 1H), 7.11 (m, 2H), 6.93 (t, J=9 Hz, 2H), 4.18 (s, 3H), 3.2-3.0 (m, 4H), 2.59 (m, 4H), 2.3-1.8 (m, 8H), 1.10 (m, 1H). Mass Spec (ES+) m/z 452.4 (M+H+, 100%).

Aufarbeitung

  1. filtrationThe mixture was filtered
  2. washthe resin was washed with dichloromethane
  3. concentrationthe filtrates were concentrated
  4. customThe residue was purified by flash chromatography
  5. washeluting with 4% methanol in dichloromethane containing 0.4% aqueous ammonium hydroxide

Quellen und Nachweise

ORD-Eintrag
ord-ed91a997d50242098006ef44ff593182
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06919356B2

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