Hydrochloric Acid → HCID 44252607, Verbindung

HRID 19120Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 19120
CC1(C)[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:38])[C@@H:15]([N:20]3[CH2:24][C:23]([O:25][C:26]4[C:31]([F:32])=[CH:30][CH:29]=[C:28]([O:33][CH2:34][CH3:35])[C:27]=4[F:36])=[CH:22][C:21]3=[O:37])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]2)[CH2:4][O:3]1.Cl>O1CCCC1.C(OCC)(=O)C>[OH:6][C@@H:5]([CH2:4][OH:3])[CH2:7][N:8]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:38])[C@@H:15]([N:20]2[CH2:24][C:23]([O:25][C:26]3[C:31]([F:32])=[CH:30][CH:29]=[C:28]([O:33][CH2:34][CH3:35])[C:27]=3[F:36])=[CH:22][C:21]2=[O:37])[CH2:16][CH:17]([CH3:18])[CH3:19])=[N:9]1

Komponenten

5

Edukt 2

HCID 313Hydrochloric AcidHCID 44252606HCID 44252606, Verbindung

Produkt 1

HCID 44252607HCID 44252607, VerbindungAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of (S)-2-[4-(3-ethoxy-2,6-difluoro-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 (prepared in Example 116, 1.140 g, 2.08 mmol) in tetrahydrofuran (100 mL) was treated with 2N aqueous hydrochloric acid (150 mL). The reaction mixture was stirred for 2.5 h at room temperature. The reaction mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate, a saturated sodium chloride solution and dried over magnesium sulfate. The mixture was filtered and evaporated and the residue purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g, 30% to 100% (9:1 dichloromethane:methanol)/hexanes) which afforded (S)-2-[4-(3-ethoxy-2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide (0.780 g, 74%) as a white solid: HR-ES-MS m/z calculated for C24H30F2N4O6, [M+H]+ 509.2206 observed 509.2206; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.6 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H), 1.35 (t, J=6.8 Hz, 3H), 1.38-1.50 (m, 1H), 1.50-1.67 (m, 1H), 1.68-1.85 (m, 1H), 3.20-3.33 (m, 2H), 3.71-3.94 (m, 2H), 4.04-4.20 (m, 3H), 4.26 (d, J=18.7 Hz, 1H), 4.63 (d, J=18.7 Hz, 1H), 4.71 (t, J=5.3 Hz, 1H), 4.87 (dd, J=10.3, 4.5 Hz, 1H), 4.94 (d, J=4.8 Hz, 1H), 5.05 (s, 1H), 6.41 (s, 1H), 7.09-7.35 (m, 2H), 7.53 (s, 1H), 10.79 (s, 1H).

Aufarbeitung

  1. washwashed with saturated sodium bicarbonate
  2. dry with materiala saturated sodium chloride solution and dried over magnesium sulfate
  3. filtrationThe mixture was filtered
  4. customevaporated
  5. customthe residue purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g, 30% to 100% (9:1 dichloromethane:methanol)/hexanes) which

Quellen und Nachweise

ORD-Eintrag
ord-627d18dde77b4f1a8fbbda03073c5112
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07741327B2

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