Methanol → (1S)-Furan-2-carboxylic acid (2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-amide

HRID 1727432Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1727432
[NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([C@@H:12]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH2:27][CH3:28])[CH:19]=1)[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH2:7]2.[O:29]1[CH:33]=[CH:32][CH:31]=[C:30]1[C:34](Cl)=[O:35].C[OH:38]>C1COCC1>[CH2:27]([O:26][C:20]1[CH:19]=[C:18]([C@H:12]([N:8]2[C:9](=[O:11])[C:10]3[C:6](=[CH:5][CH:4]=[CH:3][C:2]=3[NH:1][C:34]([C:30]3[O:29][CH:33]=[CH:32][CH:31]=3)=[O:35])[C:7]2=[O:38])[CH2:13][S:14]([CH3:17])(=[O:15])=[O:16])[CH:23]=[CH:22][C:21]=1[O:24][CH3:25])[CH3:28]

Komponenten

5

Edukt 3

HCID 887MethanolHCID 682422-Furancarbonyl chlorideHCID 66718531(S)-7-amino-2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)isoindolin-1-one

Produkt 1

HCID 67417354(1S)-Furan-2-carboxylic acid (2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-amideAusbeute 37 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of (1S)-7-amino-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethyl]-2,3-dihydro-isoindol-1-one (0.85 g, 2.0 mmol) and 2-furoyl chloride (0.40 mL, 4.1 mmol) in THF (5 mL) was heated to reflux for 17 hours. To the mixture was added methanol (4 mL). The solvent was removed in vacuo to give a solid, which was purified with chromatography (Silica Gel, EtOAc/hexane) to give (1S)-Furan-2-carboxylic acid {2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-amide as a solid (380 mg, 37% yield): mp 184-186° C.; 1H NMR (CDCl3) δ 1.45 (t, J=7 Hz, 3H, CH3), 2.86 (s, 3H, CH3), 3.76-3.80 (m, 1H, CHH), 3.83 (s, 3H, CH3), 4.10 (q, J=7 Hz, 2H, CH2), 4.56 (dd, J=10, 14 Hz, 1H, CHH), 5.90 (dd, J=5, 10 Hz, 1H, NCH), 6.57-6.58 (m, 1H, Ar), 6.81-6.84 (m, 1H, Ar), 7.10-7.13 (m, 2H, Ar), 7.27-7.28 (m, 1H, Ar), 7.47-7.50 (m, 1H, Ar), 7.63-7.69 (m, 2H,Ar), 8.84 (d, J=9 Hz, 1H, Ar), 10.39 (s, 1H, NH); 13C NMR (CDCl3) δ 14.70, 41.65, 48.74, 54.68, 55.95, 60.37, 64.55, 111.51, 112.51, 112.75, 115.76, 116.47, 118.42, 120.42, 125.03, 129.34, 131.26, 136.15, 137.25, 145.40, 147.05, 148.63, 149.75, 156.49, 167.51, 169.39. Analy, calculated for C25H24N2O8S: C 58.59; H 4.72; N 5.47. Found: C 58.34; H 4.86; N 5.38.

Aufarbeitung

  1. temperatureto reflux for 17 hours
  2. customThe solvent was removed in vacuo
  3. customto give a solid, which
  4. customwas purified with chromatography (Silica Gel, EtOAc/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-a7466c14ba69416db8d9096b289a3174
Quelldatensatz
uspto-grants-2009_02
Patentnummer
US07495112B2

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