2-Aminothiazole → HCID 21094162, Verbindung

HRID 1350318Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1350318
[C:1](/[C:4](/[C:19]1[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=1)=[CH:5]/[CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)([OH:3])=O.[S:29]1[CH:33]=[CH:32][N:31]=[C:30]1[NH2:34]>>[CH3:28][S:25]([C:22]1[CH:23]=[CH:24][C:19](/[C:4](/[C:1](=[O:3])[NH:34][C:30]2[S:29][CH:33]=[CH:32][N:31]=2)=[CH:5]\[CH:6]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[O:13])[CH2:8][CH2:7]2)=[CH:20][CH:21]=1)(=[O:27])=[O:26]

Komponenten

3

Edukt 2

HCID 21552-AminothiazoleHCID 21094163HCID 21094163, Verbindung

Produkt 1

HCID 21094162HCID 21094162, Verbindung

Versuchsvorschrift

(E)-tert-Butyl 4-[2-carboxy-2-(4-methanesulfonylphenyl)vinyl]piperidine-1-carboxylate (Preparation 35, 3.17 g, 7.7 mmol) was condensed with thiazol-2-ylamine (2.32 g, 23.2 mmol), employing the procedure described in EXAMPLE 65, to give (E)-tert-butyl 4-[2-(4-methanesulfonylphenyl)-2-(thiazol-2-ylcarbamoyl)vinyl]piperidine-1-carboxylate: m/z (ES+)=492.2 [M+H]+. TFA (20 mL) was added to a stirred solution of the abovementioned carbamate (1.40 g, 2.8 mmol) in CH2Cl2 (20 mL). After 2 h, the solution was concentrated in vacuo. The residue was dissolved in H2O, then the solution was washed with EtOAc. The aqueous layer was concentrated to furnish the trifluoroacetate salt of (E)-2-(4-methanesulfonylphenyl)-3-piperidin-4-yl-N-thiazol-2-ylacrylamide: m/z (ES+)=392.1 [M+H]+. A stirred solution of imidazole (102 mg, 1.5 mmol) in anhydrous DMF (1 mL) was treated with Me3SiCl (114 μL, 0.9 mmol). After 20 min, the above trifluoroacetate salt (150 mg, 0.3 mmol) was added. The mixture was stirred for 16 h, before being partitioned between CH2Cl2 and 1M HCl. The organic layer was dried (MgSO4), filtered, concentrated, and flash chromatographed (EtOAc-MeOH, 97:3 to 19:1). Recrystallisation (EtOAc) of the residue gave the title compound: RTA=3.05 min; m/z (ES+)=420.2 [M+H]+.

Quellen und Nachweise

ORD-Eintrag
ord-3d6951450cca483ab51dbbed02a82534
Quelldatensatz
uspto-grants-2007_05
Patentnummer
US07214681B2

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