Diisopropylethylamine → HCID 57920021, Verbindung

HRID 19417

Reaktionsgleichung

Reaktionsgleichung von HRID 19417
Cl.[OH:2][C:3]([CH3:22])([CH3:21])[CH2:4][N:5]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:20])[C@@H:12]([NH2:19])[CH2:13][C@@H:14]([O:16][CH2:17][CH3:18])[CH3:15])=[N:6]1.C(N(CC)C(C)C)(C)C.OC(C)(C)CN1C=CC(NC(=O)[C@@H](N2[CH2:51][C:50]([O:52][C:53]3[CH:58]=[CH:57][CH:56]=[C:55]([O:59][CH2:60][CH3:61])[C:54]=3[F:62])=[CH:49][C:48]2=[O:63])CC(C)C)=N1>C(#N)C>[OH:2][C:3]([CH3:22])([CH3:21])[CH2:4][N:5]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:20])[C@@H:12]([N:19]2[CH2:51][C:50]([O:52][C:53]3[CH:58]=[CH:57][CH:56]=[C:55]([O:59][CH2:60][CH3:61])[C:54]=3[F:62])=[CH:49][C:48]2=[O:63])[CH2:13][C@@H:14]([O:16][CH2:17][CH3:18])[CH3:15])=[N:6]1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 44252463HCID 44252463, VerbindungHCID 66899130(2S,4S)-2-amino-4-ethoxy-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide hydrochloride

Produkt 1

HCID 57920021HCID 57920021, VerbindungAusbeute 50,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel2×

Versuchsvorschrift

A suspension of (2S,4S)-2-amino-4-ethoxy-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide hydrochloride salt (prepared as in Example 95, 124.5 mg, 0.335 mmol) in acetonitrile (7 mL) was treated with N,N-diisopropylethylamine (0.25 mL). At this time a solution of (E)-4-bromo-3-(3-ethoxy-2-fluoro-phenoxy)-but-2-enoic acid ethyl ester (prepared as in Example 114, 117 mg, 0.337 mmol) in acetonitrile (2 mL) was added and the resulting solution refluxed for 64 h. The mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and water. The layers were separated and the organic layer was dried over anhydrous sodium sulfate. The mixture was filtered and concentrated in vacuo and the residue dissolved in tetrahydrofuran (2 mL) and transferred to an Emrys Optimizer microwave tube and microwaved at 160° C. for 1.5 h. The mixture was concentrated in vacuo and the residue was purified by ISCO flash chromatography (RediSep silica 12 g, 10% to 70% (10% methanol/dichloromethane)/hexanes,) which afforded (2S,4S)-4-ethoxy-2-[4-(3-ethoxy-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (87 mg, 50%): HR-ES-MS (m/z) calculated for C26H35FN4O6 [M+H]+ 519.2614, observed 519.2615. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.95-1.19 (m, 12H), 1.36 (t, J=6.0 Hz, 3H), 1.75-2.02 (m, 2H), 3.15-3.30 (m, 1H), 3.33 (br. s., 1H), 3.40-3.55 (m, 1H), 3.89 (br. s., 2H), 4.06-4.21 (m, 2H), 4.29 (d, J=18.4 Hz, 1H), 4.49 (d, J=18.4 Hz, 1H), 4.67 (br. s., 1H), 4.85-4.99 (m, 2H), 6.44 (br. s., 1H), 6.91-7.06 (m, 1H), 7.05-7.29 (m, 2H), 7.53 (br. s., 1H), 10.69 (br. s., 1H).

Aufarbeitung

  1. temperaturethe resulting solution refluxed for 64 h
  2. concentrationThe mixture was concentrated in vacuo
  3. customthe residue partitioned between ethyl acetate and water
  4. customThe layers were separated
  5. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  6. filtrationThe mixture was filtered
  7. concentrationconcentrated in vacuo
  8. dissolutionthe residue dissolved in tetrahydrofuran (2 mL)
  9. custommicrowaved at 160° C. for 1.5 h
  10. concentrationThe mixture was concentrated in vacuo
  11. customthe residue was purified by ISCO flash chromatography (RediSep silica 12 g, 10% to 70% (10% methanol/dichloromethane)/hexanes,) which

Quellen und Nachweise

ORD-Eintrag
ord-37f4843ab06b4492bc3cbb1a6bf59622
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07741327B2

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