Reaktion #60245

Reaktionsgleichung

cyclopropyl methyl hydroxylamine hydrochloride

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

Hunig's base

PyBOP

→

pure desired product

Ausbeute 45.0%

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

Ausbeute 45.0%

Lösungsmittel

THF

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITAfter a few minutes
2. 2
   Sonstigethe mixture is partitioned between methylene chloride and saturated NaHCO3 solution
3. 3
   SonstigeThe layers are separated
4. 4
   Waschenthe organic layer is washed with saturated NaHCO3 and brine
5. 5
   TrocknenThe organic layer is dried (Na2SO4)
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   SonstigeAfter purification
8. 8
   Waschenby FCC (elute with 20:1 methlene chloride/MeOH)

Vorschrift

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).

Quelle