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

HRID 32024Notes

Reaction equation

HRID 32024 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.[Br:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]2[C:22]([CH:32]=[O:33])=[CH:23][C:24]3[N:28]([CH3:29])[CH:27]=[N:26][C:25]=3[C:30]=2[F:31])=[C:16]([Cl:34])[CH:15]=1>C1COCC1>[Br:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]2[C:22]([CH:32]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=3)[OH:33])=[CH:23][C:24]3[N:28]([CH3:29])[CH:27]=[N:26][C:25]=3[C:30]=2[F:31])=[C:16]([Cl:34])[CH:15]=1

Participants

5

Reactant 3

HCID 79732-BromopyridineHCID 211142076-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 11442581[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazol-5-yl]-pyridin-2-yl-methanolYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

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).

Workup

  1. customThe resulting reaction mixture
  2. stirringis stirred for 1.5 hours at −78° C.
  3. customquenched with saturated aqueous NH4Cl
  4. extractionextracted with EtOAc
  5. dry with materialThe organic layer is dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. custompurified by flash chromatography (2.5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-1d2c113c3951490bb45f55b9734ac0b5
Source dataset
uspto-grants-2008_09
Patent number
US07425637B2

Reaction notes

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