Diisopropylethylamine → 3-{2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoylamino}-propionic acid ethyl ester

HRID 1967013Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1967013
COC(=O)[CH2:4][NH:5][C:6](=[O:37])[C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([O:14][C:15]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[C:21]([N:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[N:26]([CH:33]3[CH2:35][CH2:34]3)[CH2:25][CH2:24]2)=[O:22])=[CH:9][C:8]=1[Cl:36].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl.[CH2:73]([O:75][C:76](=[O:80])[CH2:77]CN)[CH3:74]>CN(C)C=O>[CH2:73]([O:75][C:76](=[O:80])[CH2:77][CH2:4][NH:5][C:6](=[O:37])[C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([O:14][C:15]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[C:21]([N:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[N:26]([CH:33]3[CH2:34][CH2:35]3)[CH2:25][CH2:24]2)=[O:22])=[CH:9][C:8]=1[Cl:36])[CH3:74]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 53312194{2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoylamino}-acetic acid methyl ester

Produkt 1

HCID 533122803-{2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoylamino}-propionic acid ethyl esterAusbeute 85 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 0.18 g (0.37 mmol) 2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoic acid (Example 29, intermediate) in 2 mL N,N-dimethylformamide were added 0.148 g (0.39 mmol) 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, commercially available, CAS RN 148893-10-1) and 0.25 mL (1.49 mmol) N,N-diisopropylethylamine. To the light brown solution 0.060 g (0.39 mmol) beta-alanine ethylester hydrochloride (commercially available, CAS RN 4244-84-2) was added and the solution was stirred at room temperature for 3.5 hours. The solution was poured on water and extracted three times with ethyl acetate. The combined organic layers were washed twice with water and brine, dried over magnesium sulfate, filtered, treated with silica gel and evaporated. The resulting powder was purified by silica gel chromatography using a MPLC system (10 g silica gel column, CombiFlash Companion, Isco Inc.) with a gradient of n-heptane:ethyl acetate (100:0 to 0:100) to afford 0.185 g (85%) of the title compound as a light brown foam. MS (ESI): m/z=583.15 [M+H]+.

Aufarbeitung

  1. additionThe solution was poured on water
  2. extractionextracted three times with ethyl acetate
  3. washThe combined organic layers were washed twice with water and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. additiontreated with silica gel
  7. customevaporated
  8. customThe resulting powder was purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-e75fee453c284702801f2238e1423858
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08420647B2

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