1-Hydroxybenzotriazole → (2E)-3-(4-Chlorophenyl)-N-[(1S)-2-oxo-2-[[2-oxo-2-[4-(3,3,3-trifluoropropyl)-1-piperazinyl]ethyl]amino]-1-(2-pyridylmethyl)ethyl]-2-propenamide

HRID 2416653

Reaktionsgleichung

Reaktionsgleichung von HRID 2416653
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]([NH:12][C@@H:13]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[C:14]([NH:16][CH2:17][C:18]([OH:20])=O)=[O:15])=[O:11])=[CH:4][CH:3]=1.Cl.Cl.[F:30][C:31]([F:41])([F:40])[CH2:32][CH2:33][N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5](/[CH:8]=[CH:9]/[C:10]([NH:12][C@@H:13]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[C:14](=[O:15])[NH:16][CH2:17][C:18](=[O:20])[N:37]2[CH2:36][CH2:35][N:34]([CH2:33][CH2:32][C:31]([F:40])([F:41])[F:30])[CH2:39][CH2:38]2)=[O:11])=[CH:6][CH:7]=1

Komponenten

7

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 226330741-(3,3,3-Trifluoropropyl)piperazine dihydrochlorideHCID 69379045[[(2S)-2-[[(2E)-3-(4-Chlorophenyl)-2-propenoyl]amino]-3-(2-pyridyl)propanoyl]amino]acetic acid

Produkt 1

HCID 69933681(2E)-3-(4-Chlorophenyl)-N-[(1S)-2-oxo-2-[[2-oxo-2-[4-(3,3,3-trifluoropropyl)-1-piperazinyl]ethyl]amino]-1-(2-pyridylmethyl)ethyl]-2-propenamideAusbeute 67,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a mixture of [[(2S)-2-[[(2E)-3-(4-chlorophenyl)-2propenoyl]amino]-3-(2-pyridyl)propanoyl]amino]acetic acid (38.8 g), 1-(3,3,3-trifluoropropyl)piperazine dihydrochloride (25.5 g), 1-hydroxybenzotriazole (14.9 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (21.1 g) in N,N-dimethylformamide (250 ml) was added dropwise N,N-diisopropylethylamine (38.3 ml) at 10° C. over 50 minutes. The mixture was warmed to room temperature and stirred for 2 hours. The reaction mixture was poured into ice-cold saturated aqueous sodium hydrogencarbonate solution (750 ml). The mixture was extracted three times with ethyl acetate (total 2500 ml) and washed successively with water (500 ml×3) and brine (200 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluent; 12% methanol in ethyl acetate) to give the title compound (37.0 g) as a white amorphous solid, which was recrystallized from ethyl acetate.

Aufarbeitung

  1. extractionThe mixture was extracted three times with ethyl acetate (total 2500 ml)
  2. washwashed successively with water (500 ml×3) and brine (200 ml)
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography (eluent; 12% methanol in ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-4bf1da8568d74c4eaca8241ffdb7a859
Quelldatensatz
uspto-grants-2004_11
Patentnummer
US06825200B1

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