Trifluoroacetic acid → HCID 178454946, Verbindung

HRID 1809985Notizen

Reaktionsgleichung

[C:1](O)(C(F)(F)F)=[O:2].[Cl:8][C:9]1[CH:26]=[CH:25][CH:24]=[CH:23][C:10]=1[CH2:11][O:12][CH2:13][CH2:14][NH:15][C@H:16]1[CH2:21][CH2:20][C@H:19]([CH3:22])[CH2:18][CH2:17]1.C([O:29][C:30](=[O:42])[C:31]([CH3:41])([CH3:40])[CH2:32][S:33][C:34]1[S:38][C:37]([NH2:39])=[N:36][CH:35]=1)C.C1N=CN(C(N2C=NC=C2)=O)C=1.[OH-].[Na+]>C1COCC1.CN(C1C=CN=CC=1)C.C(O)C>[Cl:8][C:9]1[CH:26]=[CH:25][CH:24]=[CH:23][C:10]=1[CH2:11][O:12][CH2:13][CH2:14][N:15]([C@H:16]1[CH2:17][CH2:18][C@H:19]([CH3:22])[CH2:20][CH2:21]1)[C:1](=[O:2])[NH:39][C:37]1[S:38][C:34]([S:33][CH2:32][C:31]([CH3:41])([CH3:40])[C:30]([OH:29])=[O:42])=[CH:35][N:36]=1

Komponenten

Reaktionsbedingungen

Temperatur: 75 °C

Versuchsvorschrift

The TFA salt of [2-(2-chloro-benzyloxy)-ethyl]-(trans-4-methyl-cyclohexyl)-amine (169 mg, 0.60 mmol) in THF (5 mL) was added 3-(2-amino-thiazol-5-ylsulfanyl)-2,2-dimethyl-propionic acid ethyl ester (195 mg, 0.75 mmol), CDI (243 mg, 1.50 mmol) and DMAP (3.7 mg, 0.03 mmol). The reaction mixture was stirred for 18 h. Ethanol (1 mL) and NaOH (2.5 N, 3 mL, 7.5 mmol) was added and the reaction mixture was heated to 75° C. for 5 h. The mixture was allowed to cool to rt before pH was adjusted (pH<1). The precipitate was filtered off and purified by preparative HPLC to give 170 mg (53%) of 3-{2-[3-[2-(2-Chloro-benzyloxy)-ethyl]-3-(trans-4-methyl-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-2,2-dimethyl-propionic acid.

Aufarbeitung

temperatureto cool to rt before pH
filtrationThe precipitate was filtered off
custompurified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag: ord-f215cdf8b853440ea464de3488b02eee
Quelldatensatz: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08362049B2

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