Reaktion #60271

Reaktionsgleichung

6-(4-Chloro-2-methyl-phenylamino)-7-fluoro-3-(2-oxo-ethyl)-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

Potassium carbonate

1-isocyanomethanesulfonyl-4-methyl-benzene

→

desired product

Ausbeute 50.9%

6-(4-Chloro-2-methyl-phenylamino)-7-fluoro-3-oxazol-5-ylmethyl-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

Ausbeute 50.9%

Lösungsmittel

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturat reflux for 16 hours under N2
2. 2
   Einengenconcentrated under reduced pressure
3. 3
   workup.DISSOLUTIONThe residue is dissolved in ethyl acetate
4. 4
   workup.ADDITIONpoured into a separatory funnel
5. 5
   Waschenwashed with water and brine
6. 6
   TrocknenThe combined ethyl acetate layers are dried (Na2SO4,)
7. 7
   Einengenconcentrated under reduced pressure
8. 8
   SonstigeThe resulting solid was purified by flash column chromatography (eluting with 15:1 methylene chloride:methanol)

Vorschrift

6-(4-Chloro-2-methyl-phenylamino)-7-fluoro-3-(2-oxo-ethyl)-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide (0.020 g, 0.046 mmol) is dissolved in methanol (2 mL). Potassium carbonate (0.013 g, 0.093 mmol) and 1-isocyanomethanesulfonyl-4-methyl-benzene (0.010 g, 0.051 mmol) are added. The reaction mixture is stirred at reflux for 16 hours under N2, then concentrated under reduced pressure. The residue is dissolved in ethyl acetate and poured into a separatory funnel and washed with water and brine. The combined aqueous layers are reextracted with ethyl acetate (2×). The combined ethyl acetate layers are dried (Na2SO4,) and concentrated under reduced pressure. The resulting solid was purified by flash column chromatography (eluting with 15:1 methylene chloride:methanol) to yield 0.011 g (50%) of the desired product. MS APCI (+) m/z 470, 472 (M+, Cl pattern) detected; 1H NMR (400 MHz, CDCl3) δ 10.51 (br s, 1H), 8.07 (s, 1H), 8.02 (s, 1H), 7.89 (s, 1H), 7.23 (s, 1H), 7.15 (d, 1H), 6.92 (dd, 1H), 6.31 (d, 1H), 6.11 (br s, 1H), 5.45 (s, 2H), 3.62 (d, 2H), 2.40 (s, 3H), 0.87 (m, 1H), 0.49 (m, 2H), 0.20 (m, 2H). 19F NMR (376 MHz, CDCl3) −134.54 (s).

Quelle