تفاعل #60245

معادلة التفاعل

cyclopropyl methyl hydroxylamine hydrochloride

7-Fluoro-6-(4-bromo-2-methyl-phenylamino)-1H-benzoimidazole-5-carboxylic acid

Hunig's base

PyBOP

→

pure desired product

المردود 45.0%

7-Fluoro-6-(4-bromo-2-methyl-phenylamino)-1H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

المردود 45.0%

المذيبات

THF

methylene chloride

ظروف التفاعل

المعالجة

1. 1
   workup.WAITAfter a few minutes
2. 2
   أخرىthe mixture is partitioned between methylene chloride and saturated NaHCO3 solution
3. 3
   أخرىThe layers are separated
4. 4
   غسيلthe organic layer is washed with saturated NaHCO3 and brine
5. 5
   تجفيفThe organic layer is dried (Na2SO4)
6. 6
   تركيزconcentrated under reduced pressure
7. 7
   أخرىAfter purification
8. 8
   غسيلby FCC (elute with 20:1 methlene chloride/MeOH)

الإجراء التجريبي

7-Fluoro-6-(4-bromo-2-methyl-phenylamino)-1H-benzoimidazole-5-carboxylic acid 10a (48 mg, 0.132 mmol) is dissolved in 1:1 THF: methylene chloride (1 mL) and Hunig's base (0.23 μL, 1.32 mmol) is added followed by PyBOP (82 mg, 0.158 mmol). After a few minutes, cyclopropyl methyl hydroxylamine hydrochloride (20 mg, 0.158 mmol) (WO 00/42022) is added. After the reaction is complete, the mixture is partitioned between methylene chloride and saturated NaHCO3 solution. The layers are separated and the organic layer is washed with saturated NaHCO3 and brine. The organic layer is dried (Na2SO4) and concentrated under reduced pressure. After purification by FCC (elute with 20:1 methlene chloride/MeOH), 25 mg (45%) of pure desired product is isolated: MS ESI (+) m/z 435, 433 (M+1 Br pattern) detected; MS ESI (−) m/z 433, 431 (M−1 Br pattern) detected; 1H NMR (400 MHz, CDCl3) δ 8.15 (s, 1H), 8.02 (s, 1H), 7.28 (s, 1H), 7.43 (d, 1H), 7.07 (dd, 1H), 6.36 (m, 1H), 3.70 (d, 2H), 2.38 (s, 3H), 0.86 (m, 1H), 0.41 (m, 2H), 0.13 (m, 2H); 19F NMR (376 MHz, CDCl3)-134.05 (s).

المصدر