Triethylamine → (s)-2-[4-(2-Fluoro-3-vinyl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((r)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1h-pyrazol-3-yl]-amide

HRID 19166Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 19166
[F:1][C:2]1[C:22]([CH:23]=[CH2:24])=[CH:21][CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:11](O)=[O:12])[C:7](=[O:18])[CH:6]=1.[CH3:25][C:26]1([CH3:38])[O:30][C@H:29]([CH2:31][N:32]2[CH:36]=[CH:35][C:34]([NH2:37])=[N:33]2)[CH2:28][O:27]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O>[CH3:25][C:26]1([CH3:38])[O:30][C@H:29]([CH2:31][N:32]2[CH:36]=[CH:35][C:34]([NH:37][C:11](=[O:12])[C@@H:10]([N:8]3[CH2:9][C:5]([O:4][C:3]4[CH:19]=[CH:20][CH:21]=[C:22]([CH:23]=[CH2:24])[C:2]=4[F:1])=[CH:6][C:7]3=[O:18])[CH2:14][CH:15]([CH3:17])[CH3:16])=[N:33]2)[CH2:28][O:27]1

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 59344941(R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amineHCID 66894816(S)-2-[4-(2-fluoro-3-vinyl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid

Produkt 1

HCID 44253063(s)-2-[4-(2-Fluoro-3-vinyl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((r)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1h-pyrazol-3-yl]-amideAusbeute 65,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of (S)-2-[4-(2-fluoro-3-vinyl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (0.215 g, 0.64 mmol) in N,N-dimethylformamide (5 mL) was added 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 0.153 g, 0.78 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.530 g, 1.20 mmol). The mixture was stirred at 0° C. and triethylamine (0.122 g, 1.21 mmol) was added. The mixture was stirred at room temperature for 4 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, 10% to 80% ethyl acetate/hexanes) which afforded (S)-2-[4-(2-fluoro-3-vinyl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (0.214 g, 65%) as a white solid: HR-ES-MS m/z calculated for C27H33FN4O5 [M+H]+ 513.2508, observed 513.2505, 1H NMR (300 MHz, DMSO-d6) δ ppm 1.00 0.90 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H), 1.25 (s, 3H), 1.30 (s, 3H), 1.45 (br. s., 1H), 1.49-1.67 (m, 1H), 1.67-1.84 (m, 1H), 3.73 (dd, J=8.4, 5.7 Hz, 1H), 4.00 (dd, J=8.4, 6.5 Hz, 1H), 4.04-4.18 (m, 2H), 4.23 (d, J=18.4 Hz, 1H), 4.35 (dq, J=6.0, 5.7 Hz, 1H), 4.60 (d, J=18.4 Hz, 1H), 4.81-4.93 (m, 1H), 4.91 (s, 1H), 5.52 (d, J=11.4 Hz, 1H), 6.00 (d, J=17.8 Hz, 1H), 6.44 (d, J=2.1 Hz, 1H), 6.86 (dd, J=17.8, 11.4 Hz, 1H), 7.27 (t, J=7.8 Hz, 1H), 7.42 (td, J=7.8, 1.2 Hz, 1H), 7.57-7.64 (m, 2H), 10.81 (s, 1H).

Aufarbeitung

  1. stirringThe mixture was stirred at room temperature for 4 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, 10% to 80% ethyl acetate/hexanes) which

Quellen und Nachweise

ORD-Eintrag
ord-c52cf3f0fba14590bc1dc90359f4021a
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07741327B2

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