Diisopropylethylamine → HCID 44252463, Verbindung

HRID 19113

Reaktionsgleichung

Reaktionsgleichung von HRID 19113
[CH2:1]([O:3][C:4]1[C:5]([F:25])=[C:6]([CH:22]=[CH:23][CH:24]=1)[O:7][C:8]1[CH2:12][N:11]([C@@H:13]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:14]([OH:16])=O)[C:10](=[O:21])[CH:9]=1)[CH3:2].Cl.[OH:27][C@@H:28]([CH2:58]O)[CH2:29][N:30]1[CH:34]=[CH:33][C:32]([NH:35]C(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=[N:31]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=C[C:70]=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[OH:27][C:28]([CH3:58])([CH3:70])[CH2:29][N:30]1[CH:34]=[CH:33][C:32]([NH:35][C:14](=[O:16])[C@@H:13]([N:11]2[CH2:12][C:8]([O:7][C:6]3[CH:22]=[CH:23][CH:24]=[C:4]([O:3][CH2:1][CH3:2])[C:5]=3[F:25])=[CH:9][C:10]2=[O:21])[CH2:17][CH:18]([CH3:20])[CH3:19])=[N:31]1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 66893599HCID 66893599, VerbindungHCID 66899094HMS5552 HCl

Produkt 1

HCID 44252463HCID 44252463, VerbindungAusbeute 55 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of (S)-2-[4-(3-ethoxy-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (0.460 g, 1.31 mmol) in N,N-dimethylformamide (10 mL) was added 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032, Example 80, 0.264 g, 1.70 mmol), and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (1.22 g, 2.76 mmol). The mixture was stirred at 0° C. and N,N-diisopropylethylamine (0.340 g, 2.63 mmol) was added. The mixture was stirred at room temperature for 7 h and the solvents were evaporated. The residue was treated with ethyl acetate and ammonium chloride solution, and the organic layer separated. The organic layer was washed with brine and dried over sodium sulfate. The solvents were evaporated and the residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 25 g, 30% to 100% ethyl acetate/hexanes) which afforded (S)-2-[4-(3-ethoxy-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (0.350 g, 55%) as a yellow solid: HR-ES-MS m/z calculated for C25H33FN4O5 [M+H]+ 489.2508, observed 489.2508, 1H NMR (300 MHz, DMSO-d6) δ ppm 1.00 0.90 (d, J=6.3 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H), 1.05 (br. s., 3H), 1.06 (br. s., 3H), 1.36 (t, J=6.8 Hz, 3H), 1.47 (br. s., 1H), 1.50-1.64 (m, 1H), 1.63-1.86 (m, 1H), 3.89 (s, 2H), 4.15 (q, J=6.8 Hz, 2H), 4.21 (d, J=18.7 Hz, 1H), 4.60 (d, J=18.7 Hz, 1H), 4.68 (s, 1H), 4.83-4.93 (m, 1H), 4.89 (s, 1H), 6.44 (d, J=2.1 Hz, 1H), 6.96-7.07 (m, 1H), 7.07-7.26 (m, 2H), 7.53 (d, J=2.1 Hz, 1H), 10.80 (s, 1H).

Aufarbeitung

  1. stirringThe mixture was stirred at room temperature for 7 h
  2. customthe solvents were evaporated
  3. additionThe residue was treated with ethyl acetate and ammonium chloride solution
  4. customthe organic layer separated
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvents were evaporated
  8. customthe residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 25 g, 30% to 100% ethyl acetate/hexanes) which

Quellen und Nachweise

ORD-Eintrag
ord-6f754f91f2ac44e09def8b86ec710538
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07741327B2

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