Triethylamine → Ammonia

HRID 1907148

Reaktionsgleichung

Reaktionsgleichung von HRID 1907148
[NH2:1][C@@H:2]([CH2:20][C:21]1[C:26]([CH3:27])=[CH:25][C:24]([OH:28])=[CH:23][C:22]=1[CH3:29])[C:3]([NH:5][C@@H:6]([C:8](=[O:19])[NH:9][CH2:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH3:7])=[O:4].CC1C=C(C)[N:33]([C:37](N)=[NH:38])N=1.C(N(CC)CC)C>C(O)C>[NH3:1].[NH:1]([C@@H:2]([CH2:20][C:21]1[C:22]([CH3:29])=[CH:23][C:24]([OH:28])=[CH:25][C:26]=1[CH3:27])[C:3]([NH:5][C@@H:6]([C:8](=[O:19])[NH:9][CH2:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH3:7])=[O:4])[C:37]([NH2:38])=[NH:33]

Komponenten

6

Edukt 3

HCID 8471TriethylamineHCID 975253,5-Dimethylpyrazole-1-carboxamidineHCID 98242202,6-Dimethyltyrosyl-N-(3-phenylpropyl)alaninamide

Produkt 2

HCID 222AmmoniaHCID 178429006HCID 178429006, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Versuchsvorschrift

(S)-2-Amino-3-(4-hydroxy-2,6-dimethyl-phenyl)-N-[(R)-1-(3-phenyl-propylcarbamoyl)-ethyl]-propionamide (J. Med. Chem. 1994, 37, 888) (449 mg, 1.0 mmol) and 3,5-dimethylpyrazole-1-carboxamidine (240 mg, 1.2 mmol) were heated in ethanol at 60° C. After 24 hours, triethylamine (167 μl, 1.2 mmol) was added. The reaction was heated for a further 24 hours. The solvent was evaporated and the crude material was redissolved in dichloromethane containing 2% methanol. The resulting solution was washed with a solution of citric acid followed by sodium bicarbonate solution. The organic phase was washed with brine then dried over MgSO4. The organics were filtered and evaporated leaving a small amount of a crude gum. The gum was purified using an ISCO chromatography system on a 12 g silica column using gradient elution from 95:5:0.5 to 80:20:5 DCM:MeOH:NH3 to afford the title compound as a solid in 5% yield, 20 mg. 1H NMR (400 MHz, MeOH-d4) δ : 1.18 (d, 3H), 1.75-1.82 (m, 2H), 2.21 (s, 1H), 2.49 (s, 1H), 2.58-2.63 (m, 2H), 2.95-3.02 (m, 1H), 3.10-3.24 (m, 3H), 3.28-3.32 (m, 1H), 4.18-4.22 (m, 1H), 4.35-4.40 (m, 1H), 6.51 (s, 2H), 7.08-7.28 (m, 5H). LRMS m/z 440 [M+H]+.

Aufarbeitung

  1. temperatureThe reaction was heated for a further 24 hours
  2. customThe solvent was evaporated
  3. dissolutionthe crude material was redissolved in dichloromethane containing 2% methanol
  4. washThe resulting solution was washed with a solution of citric acid
  5. washThe organic phase was washed with brine
  6. dry with materialthen dried over MgSO4
  7. filtrationThe organics were filtered
  8. customevaporated
  9. customleaving a small amount of a crude gum
  10. customThe gum was purified
  11. washelution from 95:5:0.5 to 80:20:5 DCM

Quellen und Nachweise

ORD-Eintrag
ord-903aaf3de9c84d15a539f4a521fd51da
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08598123B2

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