تفاعل #60286

معادلة التفاعل

HOBT

triethylamine

methylamine

EDCI

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid

→

pure desired product

المردود 43.0%

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methylamide

المردود 43.0%

المذيبات

N,N-dimethylformamide

ethyl acetate

water

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONThe reaction mixture is poured into a separatory funnel
2. 2
   أخرىthe layers separated
3. 3
   غسيلThe ethyl acetate layer is washed successively with aqueous saturated NH4Cl (2×), brine (1×), aqueous saturated sodium bicarbonate (2×), water (1×), and brine (1×)
4. 4
   تجفيفdried (MgSO4)
5. 5
   تركيزconcentrated under reduced pressure
6. 6
   أخرىThe resulting solid is purified by FCC (eluting with 19:1 methylene chloride:methanol)

الإجراء التجريبي

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid 10c (0.029 g, 0.076 mmol) is dissolved in N,N-dimethylformamide (1.1 mL). HOBT (0.016 g, 0.10 mmol), triethylamine (0.028 mL, 0.20 mmol), methylamine (0.059 mL, 0.12 mmol, 2 M solution in tetrahydrofuran), and EDCI (0.019 g, 0.10 mmol) are added consecutively to the reaction mixture at room temperature. The solution is stirred at room temperature for 16 hours under N2. The reaction mixture is poured into a separatory funnel and diluted with ethyl acetate and water and the layers separated. The ethyl acetate layer is washed successively with aqueous saturated NH4Cl (2×), brine (1×), aqueous saturated sodium bicarbonate (2×), water (1×), and brine (1×), dried (MgSO4) and concentrated under reduced pressure. The resulting solid is purified by FCC (eluting with 19:1 methylene chloride:methanol) to yield 0.013 g (42%) of the pure desired product. MS APCI (+) m/z 397, 399 (M+, Br pattern) detected; 1H NMR (400 MHz, DMSO-d6) δ 8.76 (broad s, 1H), 8.69 (m, 1H), 8.41 (s, 1H), 7.76 (s, 1H), 7.63 (d, 1H), 7.30 (dd, 1H), 6.50 (dd, 1H), 2.76 and 2.75 (s and s, 3H total, amide rotamers). 19F NMR (376 MHz, DMSO-d6) −132.69 (s).

المصدر