Reaktion #9717

Reaktionsgleichung

NaOH

3-(4′-amino-biphenyl-4-carbonyl)-cyclohexanecarboxylic acid methyl ester

2,6-dichloro-benzothiazole

2,6-dichlorobenzothiazole

HCl

→

cis-3-[4′-(6-chloro-benzothiazol-2-ylamino)-biphenyl-4-carbonyl]-cyclohexanecarboxylic acid

Ausbeute 23.4%

Lösungsmittel

butanol

dioxane

dioxane

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe reaction mixture was heated overnight at 90° C
2. 2
   SonstigeThe solvent was removed by rotary evaporation
3. 3
   workup.DISSOLUTIONthe residue was dissolved in DMF (2 mL)
4. 4
   Temperaturthe mixture was heated at 75° C. overnight
5. 5
   Sonstigethe crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA)

Vorschrift

To a solution of 3-(4′-amino-biphenyl-4-carbonyl)-cyclohexanecarboxylic acid methyl ester (100 mg, 0.3 mmol) in butanol (5 mL), 2,6-dichloro-benzothiazole (60 mg, 0.3 mmol) and 5 drops of 4 M HCl in dioxane were added, and the reaction mixture was heated at 90° C. for 5 h. An additional sample of 2,6-dichlorobenzothiazole (60 mg, 0.3 mmol) and 5 drops of 4 M HCl in dioxane were then added, and the reaction mixture was heated overnight at 90° C. The solvent was removed by rotary evaporation, the residue was dissolved in DMF (2 mL), 1 N aqueous NaOH (0.3 mL, 0.3 mmol) was added, and the mixture was heated at 75° C. overnight. A solution of 1 N aqueous HCl (0.3 mL, 0.3 mmol) and methanol (5 mL) were added to the reaction mixture, and the crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA) to afford cis-3-[4′-(6-chloro-benzothiazol-2-ylamino)-biphenyl-4-carbonyl]-cyclohexanecarboxylic acid as a white solid (12.6 mg, yield 23.4%). 1H NMR (300 MHz, DMSO) δ 8.05 (d, 2 H), 7.75–8.00 (m, 7 H), 7.50 (d, 1 H), 7.35 (d, 1 H), 3.25 (m, 1 H), 2.50 (m, 1 H), 2.20–1.90 (m, 4 H), 1.70–1.50 (m, 4 H); LC-MS ret. time 3.99 min (method 2), m/z 491.11 (MH+).

Quelle