3-Pyridinemethanamine → (s)-2-(3-(4-Fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-n-(pyridin-3-ylmethyl)thiazole-5-carboxamide

HRID 554950

Reaktionsgleichung

Reaktionsgleichung von HRID 554950
[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][N:7]2[C@@H:11]([CH3:12])[CH2:10][N:9]([C:13]3[S:14][C:15]([C:19](O)=[O:20])=[C:16]([CH3:18])[N:17]=3)[C:8]2=[O:22])=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[N:66]1[CH:71]=[CH:70][CH:69]=[C:68]([CH2:72][NH2:73])[CH:67]=1>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C@@H:11]([CH3:12])[CH2:10][N:9]([C:13]3[S:14][C:15]([C:19]([NH:73][CH2:72][C:68]4[CH:67]=[N:66][CH:71]=[CH:70][CH:69]=4)=[O:20])=[C:16]([CH3:18])[N:17]=3)[C:8]2=[O:22])=[CH:23][CH:24]=1

Komponenten

7

Edukt 5

HCID 310183-PyridinemethanamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57919976(S)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid

Produkt 1

HCID 44193690(s)-2-(3-(4-Fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-n-(pyridin-3-ylmethyl)thiazole-5-carboxamideAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of (S)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid (0.11 g, 0.30 mmol) in anhydrous tetrahydrofuran (3.0 mL) was added 1-hydroxybenzotriazole (HOBt) (0.08 g, 0.60 mmol), 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) (0.19 g, 0.60 mmol), N,N-diisopropylethylamine (0.23 g, 1.80 mmol) and pyridin-3-ylmethanamine (0.05 g, 0.45 mmol). The resulting mixture was stirred at ambient temperature for 16 h and concentrated in vacuo. The residue was diluted in ethyl acetate (100 mL), washed with saturated aqueous sodium bicarbonate solution (20 mL), dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography eluted with 2-8% methanol in dichloromethane to afford the title compound as a colorless solid (0.09 g, 70%): mp 67-70° C. (hexanes/diethyl ether); 1H NMR (300 MHz, DMSO-d6) δ 8.57 (t, J=5.9 Hz, 1H), 8.53 (d, J=1.9 Hz, 1H), 8.45 (dd, J=4.8, 1.5 Hz, 1H), 7.72-7.69 (m, 1H), 7.40-7.34 (m, 3H), 7.18 (dd, J=8.8, 8.8 Hz, 2H), 4.59 (d, J=15.6 Hz, 1H), 4.40 (d, J=5.9 Hz, 2H), 4.30 (d, J=15.6 Hz, 1H), 4.19 (dd, J=10.1, 9.1 Hz, 1H), 3.80-3.69 (m, 1H), 3.55 (dd, J=10.1, 6.2 Hz, 1H), 2.47 (s, 3H), 1.22 (d, J=6.2 Hz, 3H); 13C NMR (75 MHz, DMSO-d6) δ161.5 (d, 1JC-F=244 Hz), 161.8, 157.2, 154.9, 151.2, 148.8, 148.0, 135.1, 135.1, 133.1 (d, 4JC-F=3 Hz), 130.0 (d, 3JC-F=8 Hz), 123.5, 117.6, 115.4 (d, 2JC-F=21 Hz), 49.4, 48.6, 43.7, 40.4, 18.4, 17.1; MS (ES+) m/z 439.9 (M+1).

Aufarbeitung

  1. concentrationconcentrated in vacuo
  2. additionThe residue was diluted in ethyl acetate (100 mL)
  3. washwashed with saturated aqueous sodium bicarbonate solution (20 mL)
  4. dry with materialdried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by column chromatography
  8. washeluted with 2-8% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-1319e758a2df4baaa72d7461adef5afb
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08049016B2

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