Cyclopropylamine → 4-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-2-cyclopropylamino-3,5-difluorobenzoic acid ethyl ester

HRID 10288

Reaktionsgleichung

Reaktionsgleichung von HRID 10288
[CH2:1]([O:3][C:4](=[O:27])[C:5]1[CH:10]=[C:9]([F:11])[C:8]([N:12]2[CH2:16][CH2:15][C@H:14]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]2)=[C:7]([F:25])[C:6]=1F)[CH3:2].[CH:28]1([NH2:31])[CH2:30][CH2:29]1>CS(C)=O>[CH2:1]([O:3][C:4](=[O:27])[C:5]1[CH:10]=[C:9]([F:11])[C:8]([N:12]2[CH2:16][CH2:15][C@H:14]([NH:17][C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])[CH2:13]2)=[C:7]([F:25])[C:6]=1[NH:31][CH:28]1[CH2:30][CH2:29]1)[CH3:2]

Komponenten

4

Edukt 2

HCID 69828CyclopropylamineHCID 58681883(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl-2,3,5-trifluorobenzoic acid ethyl ester

Produkt 1

HCID 586819004-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-2-cyclopropylamino-3,5-difluorobenzoic acid ethyl esterAusbeute 83 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Versuchsvorschrift

A solution of 4-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-2,3,5-trifluorobenzoic acid ethyl ester (Example 2a, 1.95 g, 5.01 mmol) and cyclopropylamine (14.0 mL, 201 mmol) in dimethyl sulfoxide (5 mL) is heated in a sealed glass tube for 44.5 hours at 100° C. Compressed air is blown into the black solution to remove excess cyclopropylamine. The solution is concentrated under high vacuum and purified by flash column chromatography (1:9 ethyl acetate/hexanes) to afford the title compound (1.77 g). 1H NMR (CDCl3): δ 7.32 (dd, 1H), 4.81–4.67 (bs, 1H), 4.35–4.16 (m, 3H), 3.95–3.40 (m, 4H), 2.92–2.80 (m, 1H), 2.25–2.08 (m, 1H), 1.97–1.77 (m, 1H), 1.46 (s, 9H), 1.34 (t, 3H), 0.72–0.63 (m, 2H), 0.57–0.49 (m, 2H).

Aufarbeitung

  1. customto remove excess cyclopropylamine
  2. concentrationThe solution is concentrated under high vacuum
  3. custompurified by flash column chromatography (1:9 ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-0390ee46401f4971ae2800d3e2994491
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07094780B1

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