Triethylamine → HCID 86706102, Verbindung

HRID 2176261Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2176261
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([NH:14][C:15]([C@@H:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:35])[C@@H:24]([NH:26][C:27](=[O:34])[C@H:28]([CH:30]4[CH2:33][CH2:32][CH2:31]4)[OH:29])[CH3:25])[NH:18]3)=[O:16])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1.[CH3:36][C:37]([CH3:43])([CH:41]=[CH2:42])[C:38]([OH:40])=[O:39].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[CH:30]1([C@H:28]([OH:29])[C:27]([NH:26][C@@H:24]([CH3:25])[C:23]([N:19]2[CH2:20][CH2:21][CH2:22][C@@H:17]([C:15]([NH:14][C@@H:12]([C:8]3[CH:7]=[CH:6][C:5]4[C:10](=[CH:11][C:2](/[CH:42]=[CH:41]/[C:37]([CH3:43])([CH3:36])[C:38]([OH:40])=[O:39])=[CH:3][CH:4]=4)[N:9]=3)[CH3:13])=[O:16])[NH:18]2)=[O:35])=[O:34])[CH2:33][CH2:32][CH2:31]1

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphine2×HCID 1391222,2-Dimethyl-3-butenoic acidHCID 86706103HCID 86706103, Verbindung

Produkt 1

HCID 86706102HCID 86706102, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 9832798Tris(dibenzylideneacetone) dipalladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A solution of (S)-1-[(S)-2-((S)-2-cyclobutyl-2-hydroxy-acetylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-amide (427.5 mg, 0.782 mmol), 2,2-dimethyl-but-3-enoic acid (89.3 mg, 0.782 mmol), tri(o-tolyl)phosphine (47.6 mg, 0.156 mmol) and triethylamine (0.33 mL, 2.346 mmol) in 1,4-dioxane (10 mL) was degassed by bubbling nitrogen through for 5 minutes then warmed to 50° C. and treated with tris(dibenzylideneacetone)dipalladium(0) (71.6 mg, 0.078 mmol). After stirring at 100° C. for 1.5 h, tris(dibenzylideneacetone) dipalladium(0) (71.6 mg, 0.078 mmol) and tri(o-tolyl)phosphine (47.6 mg, 0.156 mmol) were added. After stirring for 40 minutes at 100° C., the reaction was cooled to room temperature, filtered through a pad of Celite, which was rinsed with ethyl acetate. The volatiles were removed in vacuo to provide crude title compound as an orange foam that was used without further purification. LCMS (m/z) 580.2 [M+H], Tr=2.01 min.

Aufarbeitung

  1. customby bubbling nitrogen through for 5 minutes
  2. stirringAfter stirring for 40 minutes at 100° C.
  3. temperaturethe reaction was cooled to room temperature
  4. filtrationfiltered through a pad of Celite, which
  5. washwas rinsed with ethyl acetate
  6. customThe volatiles were removed in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-3a3ca54c7ed64da89f3297267a20ede0
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09062092B2

Notizen zur Reaktion

Wird geladen…