Step 1. To a solution of tert-butyl(3-aminophenyl)carbamate 4 (1 g, 4.80 mmol) in N,N-dimethylformamide (11.08 mL) were added
1-hydroxycyclopropanecarboxylic acid (0.588 g, 5.76 mmol), propylphosphonic
anhydride solution (T3P, 50% solution in ethyl acetate), (5.5 g, 5.046
mmol), and N,N-diisopropylethylamine
(2.17 g, 2.92 mL, 168 mmol). The reaction mixture was stirred at room
temperature for 66 h. After filtration, the filtrate was purified
by HPLC (water, HCOOH/acetonitrile (0.1%)) yielding the desired product tert-butyl (3-{[(1-hydroxycyclopropyl)carbonyl]amino}phenyl)carbamate5 (0.17 g, 9.9%, 81% pure). Step 2. To a solution of tert-butyl (3-{[(1-hydroxycyclopropyl)carbonyl]amino}phenyl)carbamate 5 (0.17 g, 0.471 mmol, 81% pure) in dioxane (1 mL) was added
a solution of HCl in dioxane (4 M, 0.94 mL). The reaction mixture
was stirred at room temperature overnight. Due to an incomplete reaction,
additional HCl in dioxane (4 M) was added (0.5 mL). Stirring was continued
at room temperature for 2 h. The precipitate was filtered, washed
with dioxane, and dried at room temperature yielding N-(3-aminophenyl)-1-hydroxycyclopropanecarboxamide hydrochloride6 (0.125 g, >100%). Step 3. To a solution of 7-nitrodibenzo[b,d]furan-2-sulfonyl chloride (0.06 g,
0.192 mmol) in N,N-dimethylformamide
(1 mL) were added triethylamine (0.058 mg, 0.08 mL, 0.577 mmol), dimethylaminopyridine
(2 mg, 0.019 mmol), and N-(3-aminophenyl)-1-hydroxycyclopropanecarboxamide
hydrochloride (0.073 g, 0.289 mmol, 90%). The reaction mixture was
stirred at room temperature overnight. The reaction mixture was treated
with N,N-dimethylformamide and water
(1 mL each), filtered, and finally purified by HPLC (water, HCOOH/acetonitrile
(0.1%)) yielding the desired compound 1-hydroxy-N-(3-{[(7-nitrodibenzo[b,d]furan-2-yl)sulfonyl]amino}phenyl)cyclopropanecarboxamide
(7 ) (45 mg, 47.5%). 1H NMR (400 MHz, DMSO-d6) δ [ppm] 0.86–0.96 (m, 2H), 1.07–1.17
(m, 2H), 6.43–6.56 (br, 1H), 6.79 (br d, J = 7.35 Hz, 1H), 7.10 (t, J = 8.11 Hz, 1H), 7.26
(d, J = 8.11 Hz, 1H), 7.80 (br, 1H), 7.97–8.10
(m, 2H), 8.35 (dd, J = 8.52, 1.52 Hz, 1H), 8.56 (d, J = 8.60 Hz, 1H), 8.71 (d, J = 1.57 Hz,
1H), 8.91 (br, 1H), 9.78 (br, 1H), 10.40 (br, 1H).
1-hydroxycyclopropanecarboxylic acid (0.588 g, 5.76 mmol), propylphosphonic
anhydride solution (T3P, 50% solution in ethyl acetate), (5.5 g, 5.046
mmol), and N,N-diisopropylethylamine
(2.17 g, 2.92 mL, 168 mmol). The reaction mixture was stirred at room
temperature for 66 h. After filtration, the filtrate was purified
by HPLC (water, HCOOH/acetonitrile (0.1%)) yielding the desired product tert-butyl (3-{[(1-hydroxycyclopropyl)carbonyl]amino}phenyl)carbamate
a solution of HCl in dioxane (4 M, 0.94 mL). The reaction mixture
was stirred at room temperature overnight. Due to an incomplete reaction,
additional HCl in dioxane (4 M) was added (0.5 mL). Stirring was continued
at room temperature for 2 h. The precipitate was filtered, washed
with dioxane, and dried at room temperature yielding N-(3-aminophenyl)-1-hydroxycyclopropanecarboxamide hydrochloride
0.192 mmol) in N,N-dimethylformamide
(1 mL) were added triethylamine (0.058 mg, 0.08 mL, 0.577 mmol), dimethylaminopyridine
(2 mg, 0.019 mmol), and N-(3-aminophenyl)-1-hydroxycyclopropanecarboxamide
hydrochloride (0.073 g, 0.289 mmol, 90%). The reaction mixture was
stirred at room temperature overnight. The reaction mixture was treated
with N,N-dimethylformamide and water
(1 mL each), filtered, and finally purified by HPLC (water, HCOOH/acetonitrile
(0.1%)) yielding the desired compound 1-hydroxy-N-(3-{[(7-nitrodibenzo[b,d]furan-2-yl)sulfonyl]amino}phenyl)cyclopropanecarboxamide
(
(m, 2H), 6.43–6.56 (br, 1H), 6.79 (br d, J = 7.35 Hz, 1H), 7.10 (t, J = 8.11 Hz, 1H), 7.26
(d, J = 8.11 Hz, 1H), 7.80 (br, 1H), 7.97–8.10
(m, 2H), 8.35 (dd, J = 8.52, 1.52 Hz, 1H), 8.56 (d, J = 8.60 Hz, 1H), 8.71 (d, J = 1.57 Hz,
1H), 8.91 (br, 1H), 9.78 (br, 1H), 10.40 (br, 1H).
