1-Hydroxybenzotriazole → (RS)-1-[2-(4,5-Difluoro-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluoro-phenyl)-2-hydroxymethyl-thiazol-4-yl]-methanone

HRID 598584Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 598584
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH2:13][OH:14])=[N:10][C:9]=2[C:15]([OH:17])=O)=[CH:4][CH:3]=1.[F:18][C:19]1[C:27]2[N:26]=[C:25]([CH2:28][CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][NH:30]3)[NH:24][C:23]=2[CH:22]=[CH:21][C:20]=1[F:35].CCN=C=NCCCN(C)C.Cl.ON1C2C=CC=CC=2N=N1>CN(C=O)C.C(OCC)C.CO.ClCCl>[F:18][C:19]1[C:27]2[N:26]=[C:25]([CH2:28][CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][N:30]3[C:15]([C:9]3[N:10]=[C:11]([CH2:13][OH:14])[S:12][C:8]=3[C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[O:17])[NH:24][C:23]=2[CH:22]=[CH:21][C:20]=1[F:35]

Komponenten

8

Edukt 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 17973676(RS)-4,5-Difluoro-2-piperidin-2-ylmethyl-1H-benzoimidazoleHCID 234501385-(4-Fluoro-phenyl)-2-hydroxymethyl-thiazole-4-carboxylic acid

Produkt 1

HCID 66968516(RS)-1-[2-(4,5-Difluoro-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluoro-phenyl)-2-hydroxymethyl-thiazol-4-yl]-methanoneAusbeute 33 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 21226129Dichloromethane methanolLösungsmittel

Versuchsvorschrift

A stirring solution of 5-(4-fluoro-phenyl)-2-hydroxymethyl-thiazole-4-carboxylic acid (320 mg, 1.0 mmol, 80% pure) and (RS)-4,5-difluoro-2-piperidin-2-ylmethyl-1H-benzoimidazole, D21 (250 mg, 1.0 mmol) in DMF (10 ml) was treated with EDC.HCl (194 mg, 1.0 mmol) and 1-hydroxybenzotriazole (50 mg, 0.4 mmol). The reaction mixture was stirred at room temperature, under argon for 16 h. The resulting solution was diluted with diethyl ether then washed with saturated aqueous NaHCO3, water (3×) and brine. Drying (MgSO4) and removal of the solvent in vacuo afforded an orange gum. Chromatography (silica gel, 0-2% methanol-dichloromethane) afforded the title compound as an orange powder (160 mg, 33%). Mass spectrum (Electrospray LC/MS) Found 487 (MH+). C24H21F3N4O2S requires 486.

Aufarbeitung

  1. washthen washed with saturated aqueous NaHCO3, water (3×) and brine
  2. customDrying
  3. custom(MgSO4) and removal of the solvent in vacuo
  4. customafforded an orange gum

Quellen und Nachweise

ORD-Eintrag
ord-cbe11634ff8e458e85fde3ad0032b459
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07897618B2

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