Dimethyl Sulfoxide → HCID 178498839, Verbindung

HRID 707364Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 707364
Cl.[NH2:2][C@H:3]1[CH2:6][C@H:5]([N:7]2[C:11]3=[N:12][CH:13]=[CH:14][N:15]=[C:10]3[N:9]([CH:16]3[CH2:18][CH2:17]3)[C:8]2=[O:19])[CH2:4]1.ClC1SC=C([C:26]([O:28][CH3:29])=[O:27])N=1.C([N:33]([CH:36]([CH3:38])C)[CH2:34]C)(C)C.C[S:40](C)=O>O>[CH:16]1([N:9]2[C:10]3[C:11](=[N:12][CH:13]=[CH:14][N:15]=3)[N:7]([C@H:5]3[CH2:6][C@H:3]([NH:2][C:34]4[S:40][C:38]([C:26]([O:28][CH3:29])=[O:27])=[CH:36][N:33]=4)[CH2:4]3)[C:8]2=[O:19])[CH2:17][CH2:18]1

Komponenten

6

Edukt 4

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 7213135Methyl 2-chloro-4-thiazolecarboxylateHCID 178479284HCID 178479284, Verbindung2×

Produkt 1

HCID 178498839HCID 178498839, VerbindungAusbeute 27,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

A solution of 1-(trans-3-aminocyclobutyl)-3-cyclopropyl-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride (Intermediate 79, 1.00 g, 3.55 mmol), methyl 2-chloro-4-thiazolecarboxylate (0.820 g, 4.61 mmol), and diisopropylethylamine (3.09 mL, 17.75 mmol) in DMSO (10 mL) was stirred at 120° C. for 18 h. The reaction was allowed to cool to room temperature, diluted with water and extracted with EtOAc. EtOAc was concentrated and residue purified with ISCO using silica gel column eluting with 0-70% EtOAc/hexane to give the title compound methyl 2-((trans-3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-1-yl)cyclobutyl)amino)thiazole-5-carboxylate (0.380 g, 0.983 mmol, 27.7% yield). m/z: 387.0 (M+1); 1H NMR (400 MHz, DMSO-d6) δ: ppm 8.38 (d, J=6.46 Hz, 1 H), 7.99 (q, J=3.26 Hz, 2 H), 7.60 (s, 1 H), 5.15 (t, J=8.31 Hz, 1 H), 4.28-4.47 (m, 1 H), 3.77 (s, 3 H), 3.18-3.30 (m, 2 H), 2.88-3.07 (m, 1 H), 2.34-2.47 (m, 2 H), 0.91-1.13 (m, 4 H).

Aufarbeitung

  1. extractionextracted with EtOAc
  2. concentrationEtOAc was concentrated
  3. customresidue purified with ISCO
  4. washeluting with 0-70% EtOAc/hexane

Quellen und Nachweise

ORD-Eintrag
ord-a5aea8449a054be9b1bca879b00ab681
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09174992B2

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