Pyrazole → 3-[2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazole-1-carboxylic acid methylamide

HRID 546050

Reaktionsgleichung

Reaktionsgleichung von HRID 546050
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:21][CH:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][NH:18][N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[CH3:27][N:28]=[C:29]=[O:30].N1C=CC=N1>CN(C)C=O.C(OCC)(=O)C>[CH3:27][NH:28][C:29]([N:18]1[CH:19]=[CH:20][C:16]([NH:15][C:13](=[O:14])[C@@H:12]([C:4]2[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[C:2]([Cl:1])[CH:3]=2)[CH2:21][CH:22]2[CH2:23][CH2:24][CH2:25][CH2:26]2)=[N:17]1)=[O:30]

Komponenten

6

Edukt 3

HCID 1048PyrazoleHCID 12228Methyl IsocyanateHCID 178504752HCID 178504752, Verbindung

Produkt 1

HCID 671906283-[2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazole-1-carboxylic acid methylamideAusbeute 14 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

The 2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1H-pyrazol-3-yl)-propionamide (prepared in example 2, 115 mg, 0.29 mmol) was dissolved in anhydrous N,N-dimethylformamide (2 mL) and warmed to 60° C. in a sealed vial. Methyl-isocyanate (165 mg, 2.90 mmol) was transferred via syringe to the pyrazole solution. The mixture was heated at 60° C. for 2 h while stirring in the sealed vial. The mixture was diluted with ethyl acetate (25 mL), washed with water (2×15 mL), saturated aqueous brine solution (15 mL), dried over magnesium sulfate and concentrated in vacuo. Purification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 15% ethyl acetate/hexanes to 100% ethyl acetate/hexanes) afforded 3-[2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazole-1-carboxylic acid methylamide (18 mg, 14%) as a white powder: ESI-LRMS m/e calcd for C20H25ClN4O4S [M+] 452.1, found 453.2 [M+H+], 395.9 [M−CONCH3+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.04-1.23 (m, 2H, CH2), 1.43-1.97 (m, 8H, 4×CH2), 2.11-2.34 (m, 1H, CH), 2.95 (d, J=4.6 Hz, 3H, NCH3), 3.27 (s, 3H, SO2CH3), 3.65 (t, J=7.5 Hz, 1H, CH), 6.81 (q, J=4.6 Hz, 1H, NH), 6.84 (d, J=2.7 Hz, 1H, Ar), 7.46 (dd, Jo=8.2, Jm=1.7 Hz, 1H, Ar), 7.60 (d, Jm=1.7 Hz, 1H, Ar), 8.04 (d, Jo=8.2 Hz, 1 H, Ar), 8.07 (d, J=2.7 Hz, 1H, Ar), 8.32 (s, 1H, NH).

Aufarbeitung

  1. temperatureThe mixture was heated at 60° C. for 2 h
  2. washwashed with water (2×15 mL), saturated aqueous brine solution (15 mL)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 15% ethyl acetate/hexanes to 100% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-14b019cb89a6455aa1a477ca36027f5a
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07935699B2

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