Diisopropylethylamine → N-[(2S)-3-(2-Ethyl-4-{5-[2-(1-ethyl-propyl)-6-methoxy-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenoxy)-2-hydroxy-propyl]-2-hydroxy-acetamide

HRID 245105Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 245105
[CH2:1]([CH:3]([C:6]1[CH:7]=[C:8]([CH:12]=[C:13]([O:15][CH3:16])[N:14]=1)[C:9]([OH:11])=O)[CH2:4][CH3:5])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:48]([C:50]1[CH:65]=[C:64]([C:66](=[NH:69])[NH:67]O)[CH:63]=[C:62]([CH3:70])[C:51]=1[O:52][CH2:53][C@@H:54]([OH:61])[CH2:55][NH:56][C:57](=[O:60])[CH2:58][OH:59])[CH3:49]>CN(C=O)C.C1COCC1.CC(=O)OCC>[CH2:48]([C:50]1[CH:65]=[C:64]([C:66]2[N:69]=[C:9]([C:8]3[CH:12]=[C:13]([O:15][CH3:16])[N:14]=[C:6]([CH:3]([CH2:1][CH3:2])[CH2:4][CH3:5])[CH:7]=3)[O:11][N:67]=2)[CH:63]=[C:62]([CH3:70])[C:51]=1[O:52][CH2:53][C@@H:54]([OH:61])[CH2:55][NH:56][C:57](=[O:60])[CH2:58][OH:59])[CH3:49]

Komponenten

8

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 584181082-(1-Ethylpropyl)-6-methoxyisonicotinic acidHCID 178436630HCID 178436630, Verbindung

Produkt 1

HCID 49871977N-[(2S)-3-(2-Ethyl-4-{5-[2-(1-ethyl-propyl)-6-methoxy-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenoxy)-2-hydroxy-propyl]-2-hydroxy-acetamideAusbeute 45,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 2-(1-ethyl-propyl)-6-methoxy-isonicotinic acid (200 mg, 770 μmol) in DMF (3 mL) and THF (10 mL), DIPEA (200 mg, 1.54 mmol) and TBTU (272 mg, 847 μmol) are added. The mixture is stirred at rt for 10 min before N—((S)-3-[2-ethyl-4-(N-hydroxycarbamimidoyl)-6-methyl-phenoxy]-2-hydroxy-propyl)-2-hydroxy-acetamide (251 mg, 770 μmol) is added. The mixture is stirred at rt for 30 min, diluted with EA (100 mL) and washed with brine. The org. extract is concentrated and the residue is dissolved in dioxane (50 mL). The mixture is stirred at 100° C. for 2 h before it is concentrated. The crude product is purified on prep. TLC plates using DCM containing 10% of methanol to give the title compound (180 mg) as a resin; LC-MS: tR=1.08 min, [M+H]+=513.13; 1H NMR (CDCl3): δ0.84 (t, J=7.3 Hz, 6H), 1.31 (t, J=7.5 Hz, 3H), 1.68-1.88 (m, 4H), 2.38 (s, 3H), 2.55-2.64 (m, 1H), 2.74 (q, J=7.5 Hz, 2H), 3.50-3.58 (m, 1H), 3.74-3.94 (m, 4H), 4.01 (s, 3H), 4.17-4.25 (m, 3H), 7.09 (t br, J=5.5 Hz, 1H), 7.31 (d, J=1.3 Hz, 1H), 7.43 (d, J=1.3 Hz, 1H), 7.86 (d, J=1.8 Hz), 7.88 (d, J=2.0 Hz).

Aufarbeitung

  1. additionis added
  2. washwashed with brine
  3. extractionextract
  4. concentrationis concentrated
  5. dissolutionthe residue is dissolved in dioxane (50 mL)
  6. stirringThe mixture is stirred at 100° C. for 2 h before it
  7. concentrationis concentrated
  8. customThe crude product is purified on prep

Quellen und Nachweise

ORD-Eintrag
ord-a8edd5b4253c41df88f5009f09215324
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658675B2

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