반응 #60245

반응 방정식

cyclopropyl methyl hydroxylamine hydrochloride

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

Hunig's base

PyBOP

→

pure desired product

수율 45.0%

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

수율 45.0%

용매

THF

methylene chloride

반응 조건

후처리

1. 1
   workup.WAITAfter a few minutes
2. 2
   기타the mixture is partitioned between methylene chloride and saturated NaHCO3 solution
3. 3
   기타The layers are separated
4. 4
   세척the organic layer is washed with saturated NaHCO3 and brine
5. 5
   건조The organic layer is dried (Na2SO4)
6. 6
   농축concentrated under reduced pressure
7. 7
   기타After purification
8. 8
   세척by FCC (elute with 20:1 methlene chloride/MeOH)

실험 절차

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).

출처