Ammonia → 3-Cyclobutyl-1-quinolin-7-ylimidazo[1,5-a]pyrazin-8-ylamine

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Reaktionsgleichung

[NH3:1].C(=O)=O.CC(C)=O.Cl[C:10]1[C:11]2[N:12]([C:16]([CH:29]3[CH2:32][CH2:31][CH2:30]3)=[N:17][C:18]=2[C:19]2[CH:28]=[C:27]3[C:22]([CH:23]=[CH:24][CH:25]=[N:26]3)=[CH:21][CH:20]=2)[CH:13]=[CH:14][N:15]=1>N.CC(O)C>[CH:29]1([C:16]2[N:12]3[CH:13]=[CH:14][N:15]=[C:10]([NH2:1])[C:11]3=[C:18]([C:19]3[CH:28]=[C:27]4[C:22]([CH:23]=[CH:24][CH:25]=[N:26]4)=[CH:21][CH:20]=3)[N:17]=2)[CH2:32][CH2:31][CH2:30]1

Komponenten

Reaktionsbedingungen

Temperatur: 110 °C

Versuchsvorschrift

Gaseous NH3 was condensed into a cooled (dry ice/acetone) solution of 7-(8-chloro-3-cyclobutylimidazo[1,5-a]pyrazin-1-yl)-quinoline (203.2 mg, 0.607 mmol) in 2M NH3/iPrOH (6 mL) in a pressure tube until the volume was doubled, then the tube was sealed and heated to 110° C. (bath temp.) for 19 h. The ammonia was evaporated, the crude material was adsorbed onto Hydromatrix and chromatographed on silica gel [Jones Flashmaster, 10 g/70 mL cartridge, eluting with CH2Cl2 1:1 (1-6)→2% MeOH in CH2Cl2 (7-27)→4% MeOH in CH2Cl2 (28-37)→5% MeOH in CH2Cl2 (38-53)→7% MeOH in CH2Cl2 (54-67)], yielding the title compound as a yellow solid, >98% pure by HPLC, mp. 94-96° C.; 1H NMR (CDCl3, 400 MHz) δ 2.00-2.10 (m, 1H), 2.12-2.25 (m, 1H), 2.47-2.57 (m, 2H), 2.61-2.73 (m, 2H), 3.85 (quint, J=8.4 Hz, 1H), 5.23 (brs, 2H), 7.10 (d, J=4.4 Hz, 1H), 7.16 (d, J=4.4 Hz, 1H), 7.44 (dd, J=4.2, 8.2 Hz, 1H), 7.95 (d, J=8.4 Hz, 1H), 8.00 (d, J=8.4 Hz, 1H), 8.22 (d, J=8.2 Hz, 1H), 8.36 (s, 1H), 8.95-9.00 (m, 1H); MS (ES+): m/z 316.2 (30) [MH+].

Aufarbeitung

customcondensed into
customthe tube was sealed
customThe ammonia was evaporated
customchromatographed on silica gel [Jones Flashmaster, 10 g/70 mL cartridge
washeluting with CH2Cl2 1:1 (1-6)

Quellen und Nachweise

ORD-Eintrag: ord-3db5713f9d3e46d1a7254d30c05ee967
Quelldatensatz: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08653268B2

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