proline dl-form → (1aR,5aR)-2-(5-Methoxy-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic Acid Ethyl Ester

HRID 1623921Notizen

Reaktionsgleichung

[CH2:1]([O:3][C:4]([C:6]1[C:7]2[CH2:8][C@H:9]3[CH2:14][C@H:10]3[C:11]=2[NH:12][N:13]=1)=[O:5])[CH3:2].I[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][N:17]=1.N1CCCC1C(O)=O.C(=O)([O-])[O-].[K+].[K+]>[Cu]I>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[CH2:8][C@H:9]3[CH2:14][C@H:10]3[C:11]=2[N:12]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][N:17]=2)[N:13]=1)=[O:5])[CH3:2]

Komponenten

Reaktionsbedingungen

Temperatur: 75 °C

Versuchsvorschrift

A 20 mL scintillation vial was charged with (1aR,5aR)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester (492 mg, 2.56 mmol), 2-iodo-5-methoxypyridine (662 mg, 2.82 mmol), DL-proline (58.9 mg, 0.512 mmol), copper(I) iodide (48.7 mg, 0.256 mmol), and potassium carbonate (708 mg, 5.12 mmol). The vial was flushed with nitrogen, and added DMSO (15 mL). The reaction was stirred under nitrogen at 75° C. for 15 h. The reaction was filtered then purified by HPLC to provide the title compound (279 mg) as a white solid. LCMS m/z=300.3 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 0.45 (td, J=4.7, 3.3 Hz, 1H), 1.23 (td, J=8.0, 4.8 Hz, 1H), 1.39 (t, J=7.2 Hz, 3H), 2.21-2.27 (m, 1H), 2.77-2.82 (m, 1H), 2.85 (d, J=16.6 Hz, 1H), 2.97 (dd, J=16.6, 6.4 Hz, 1H), 3.90 (s, 3H), 4.38 (q, J=7.2 Hz, 2H), 7.34 (dd, J=8.8, 2.9 Hz, 1H), 7.98 (dd, J=9.0, 0.6 Hz, 1H), 8.13 (dd, J=3.0, 0.5 Hz, 1H).

Aufarbeitung

customThe vial was flushed with nitrogen
additionadded DMSO (15 mL)
filtrationThe reaction was filtered
customthen purified by HPLC

Quellen und Nachweise

ORD-Eintrag: ord-8b1267976008428abed1f23340c02494
Quelldatensatz: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08778950B2

Notizen zur Reaktion

Wird geladen…