Diisopropylethylamine → HCID 52950836, Verbindung

HRID 634037Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 634037
Cl.[O:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[CH:4]=[C:3]1[CH:11]1[CH2:14][NH:13][CH2:12]1.Cl.[CH3:16][N:17]1[CH2:22][CH2:21][C:20]2([CH2:31][C:30]3[C:25](=[N:26][CH:27]=[C:28](/[CH:32]=[CH:33]/[C:34](O)=[O:35])[CH:29]=3)[NH:24][C:23]2=[O:37])[CH2:19][CH2:18]1.CCN=C=NCCCN(C)C.Cl.C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[O:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[CH:4]=[C:3]1[CH:11]1[CH2:12][N:13]([C:34](=[O:35])/[CH:33]=[CH:32]/[C:28]2[CH:29]=[C:30]3[C:25](=[N:26][CH:27]=2)[NH:24][C:23](=[O:37])[C:20]2([CH2:21][CH2:22][N:17]([CH3:16])[CH2:18][CH2:19]2)[CH2:31]3)[CH2:14]1

Komponenten

7

Edukt 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67154551HCID 67154551, VerbindungHCID 67154626HCID 67154626, Verbindung

Produkt 1

HCID 52950836HCID 52950836, VerbindungAusbeute 9,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 3-(benzofuran-2-yl)azetidine hydrochloride (30 mg, 0.086 mmol) and (E)-3-(1′-methyl-2-oxo-2,4-dihydro-1H-spiro[[1,8]naphthyridine-3,4′-piperidine]-6-yl)acrylic acid hydrochloride (20 mg, 0.059 mmol) in dry DMF (4 mL) were added EDCI.HCl (17.02 mg, 0.089 mmol), HOAt (12.09 mg, 0.089 mmol) and DIPEA (51 μL, 0.296 mmol). The reaction was stirred at room temperature overnight. The mixture was partitioned between dichloromethane and H2O, the layers were separated and the aqueous layer was extracted with dichloromethane (2×5 mL). The combined organic layers were washed with brine (3×3 mL), dried over Na2SO4 and concentrated. The residue was chromatographic purified (silica gel, eluent dichloromethane/7M NH3 in MeOH 98:2 to 95:5). The residue was further purified by preparative LCMS (Waters X-Bridge 50×19 mm 5 μm ODB in combination with Waters X-Bridge guard 10×19 mm 5 μm, at 25 ml/min flow rate; detection of product by mass and UV signal; eluent 10 mM ammonia in milliQ water to 10 mM ammonia in MeCN 5% to 95% gradient), to yield the title compound (2.6 mg, 9.6%).

Aufarbeitung

  1. customThe mixture was partitioned between dichloromethane and H2O
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with dichloromethane (2×5 mL)
  4. washThe combined organic layers were washed with brine (3×3 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was chromatographic purified (silica gel, eluent dichloromethane/7M NH3 in MeOH 98:2 to 95:5)
  8. customThe residue was further purified by preparative LCMS (Waters X-Bridge 50×19 mm 5 μm ODB in combination with Waters X-Bridge guard 10×19 mm 5 μm, at 25 ml/min flow rate; detection of product by mass and UV signal; eluent 10 mM ammonia in milliQ water to 10 mM ammonia in MeCN 5% to 95% gradient)

Quellen und Nachweise

ORD-Eintrag
ord-32909be7ea10475793babf49b193ad8e
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321769B2

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