1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-(4-fluorophenyl)-1-{2-oxo-2-[5-(trifluoromethyl)-1,3-dihydro-2H-isoindol-2-yl]ethyl}pyrrolidin-2-one

HRID 1667253Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1667253
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]([OH:16])=O)[C:9]2=[O:17])=[CH:4][CH:3]=1.Br.[F:19][C:20]([F:31])([F:30])[C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[CH2:26][NH:25][CH2:24]2.C(N=C=NCCCN(C)C)C>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:12][CH2:11][N:10]([CH2:13][C:14](=[O:16])[N:25]3[CH2:24][C:23]4[C:27](=[CH:28][CH:29]=[C:21]([C:20]([F:19])([F:31])[F:30])[CH:22]=4)[CH2:26]3)[C:9]2=[O:17])=[CH:6][CH:7]=1

Komponenten

5

Edukt 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 673576422-(3-(4-Fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acidHCID 67359038HCID 67359038, Verbindung

Produkt 1

HCID 674425073-(4-fluorophenyl)-1-{2-oxo-2-[5-(trifluoromethyl)-1,3-dihydro-2H-isoindol-2-yl]ethyl}pyrrolidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a suspension of 2-(3-(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (0.102 g, 0.430 mmol; Example 216A) and 5-(trifluoromethyl)isoindoline hydrobromide (0.127 g, 0.473 mmol) in dichloromethane (0.75 mL) was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.114 mL, 0.645 mmol) and the reaction was stirred at room temperature. After stirring for 18 hours, the reaction was loaded onto a GraceResolv™ 4 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 5% ethyl acetate/hexanes to 100% ethyl acetate/hexanes (Flow=20 mL/minute) over 30 minutes to give the title compound. 1H NMR (300 MHz, CDCl3) δ 7.58 (dd, J=8.5, 12.6, 2H), 7.42 (dd, J=8.1, 15.3, 1H), 7.36-7.21 (m, 2H), 7.12-6.93 (m, 2H), 4.91 (d, J=17.7, 4H), 4.29 (d, J=16.1, 1H), 4.17 (d, J=16.2, 1H), 3.85-3.54 (m, 3H), 2.72-2.50 (m, 1H), 2.19 (ddd, J=8.5, 12.9, 16.3, 1H); MS (ESI+) m/z 407.0 (M+H)+.

Aufarbeitung

  1. stirringAfter stirring for 18 hours
  2. washthe product eluted with a gradient of 5% ethyl acetate/hexanes to 100% ethyl acetate/hexanes (Flow=20 mL/minute) over 30 minutes

Quellen und Nachweise

ORD-Eintrag
ord-a13140e7e2324ed684e5e3b455b5642a
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08044069B2

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