Reaktion #60302

Reaktionsgleichung

6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carbaldehyde

2-bromopyridine

n-BuLi

→

desired product

Ausbeute 62.0%

[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazol-5-yl]-pyridin-2-yl-methanol

Ausbeute 62.0%

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe resulting reaction mixture
2. 2
   workup.STIRRINGis stirred for 1.5 hours at −78° C.
3. 3
   Sonstigequenched with saturated aqueous NH4Cl
4. 4
   Extraktionextracted with EtOAc
5. 5
   TrocknenThe organic layer is dried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated in vacuo
8. 8
   Sonstigepurified by flash chromatography (2.5% MeOH in CH2Cl2)

Vorschrift

To a solution of 2-bromopyridine (0.10 mL, 1.04 mmol) in THF (3 mL) at −78° C. is added n-BuLi (0.39 mL, 0.98 mmol, 2.5 M solution in hexane). After stirring for 10 minutes at −78° C., a solution of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carbaldehyde 10h (25 mg, 0.064 mmol) in THF (1 mL) is added. The resulting reaction mixture is stirred for 1.5 hours at −78° C., quenched with saturated aqueous NH4Cl, and extracted with EtOAc. The organic layer is dried over MgSO4, filtered, concentrated in vacuo, and purified by flash chromatography (2.5% MeOH in CH2Cl2) to afford the desired product (18 mg, 62%): MS APCI (+) m/z 461, 463 (M+, Br pattern) detected; 1H NMR (400 MHz, CD3OD) δ 8.31 (d, 1H), 8.16 (s, 1H), 7.65 (m, 3H), 7.38 (d, 1H), 7.10 (m, 1H), 7.00 (dd, 1H), 6.11 (dd, 1H), 6.05 (s, 1H), 3.94 (s, 3H); 19F NMR (376 MHz, CD3OD) −135.79 (s).

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