Diisopropylethylamine → (R)-tert-butyl 4-(tert-butoxycarbonylamino)-7-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-ylamino)-5-oxoheptanoate

HRID 1782185Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1782185
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:19](=[O:22])[CH:20]=[CH2:21])[CH2:10][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[Cl:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[C:26]=1[C:32]1[CH:36]=[C:35]([C:37]2[CH:42]=[C:41]([NH2:43])[CH:40]=[CH:39][N:38]=2)[O:34][N:33]=1.C(N(C(C)C)CC)(C)C>C(#N)C.ClCCl>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:19](=[O:22])[CH2:20][CH2:21][NH:43][C:41]1[CH:40]=[CH:39][N:38]=[C:37]([C:35]2[O:34][N:33]=[C:32]([C:26]3[C:25]([Cl:24])=[CH:30][CH:29]=[CH:28][C:27]=3[Cl:31])[CH:36]=2)[CH:42]=1)[CH2:10][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 69053436HCID 69053436, VerbindungHCID 86608878(S)-tert-butyl 4-(tert-butoxycarbonylamino)-5-oxohept-6-enoate

Produkt 1

HCID 57588345(R)-tert-butyl 4-(tert-butoxycarbonylamino)-7-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-ylamino)-5-oxoheptanoateAusbeute 43,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
89 °C

Versuchsvorschrift

(S)-tert-butyl 4-(tert-butoxycarbonylamino)-5-oxohept-6-enoate (0.94 g) and 2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-amine hydrochloride salt (0.40 g) were dissolved in acetonitrile (4 mL). Diisopropylethylamine (0.52 mL) was added and the mixture wad heated at 89° C. for 25 h. The mixture was cooled to room temperature, diluted with dichloromethane and washed with brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography, on silica gel, eluting with 0.5:99.5 methanol:dichloromethane then 5:95 methanol:dichloromethane to yield (R)-tert-butyl 4-(tert-butoxycarbonylamino)-7-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-ylamino)-5-oxoheptanoate (316 mg) as a beige foam. 1H NMR (CDCl3): 8.25 (m, 1H), 7.40 (m, 2H), 7.30 (m, 1H), 7.17 (m, 1H), 6.98 (m, 1H), 6.47 (m, 1H), 5.20 (m, 1H), 5.00 (m, 1H), 4.22 (m, 1H), 3.59 (m, 2H), 2.90 (m, 2H), 2.32 (m, 2H), 2.10 (m, 1H), 1.83 (m, 1H), 1.45 ppm (s, 18H). MW=619 confirmed by LC-MS, tr=13.23 min (Method Y) MH+=617-621.

Aufarbeitung

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed with brine
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by flash column chromatography, on silica gel
  7. washeluting with 0.5:99.5 methanol

Quellen und Nachweise

ORD-Eintrag
ord-ec3e3b0c7a8244189344af93d1df6ba5
Quelldatensatz
uspto-grants-2009_03
Patentnummer
US07498353B2

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