Chloromethyl Methyl Ether → 7-(2-Fluoro-4-nitrophenoxy)-2-(1-(methoxymethyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridine

HRID 418623Notes

Reaction equation

HRID 418623 reaction equation
[F:1][C:2]1[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[N:15]=[CH:16][NH:17][CH:18]=3)[S:13][C:6]=12.[H-].[Na+].[CH2:28](Cl)[O:29][CH3:30]>CN(C=O)C>[F:1][C:2]1[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[N:15]=[CH:16][N:17]([CH2:28][O:29][CH3:30])[CH:18]=3)[S:13][C:6]=12

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 178526697HCID 178526697, compound

Product 1

HCID 587902607-(2-Fluoro-4-nitrophenoxy)-2-(1-(methoxymethyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridineYield 37.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 7-(2-fluoro-4-nitrophenoxy)-2-(1H-imidazol-4-yl)thieno[3,2-b]pyridine (93) (WO 2006010264) (300 mg, 0.84 mmol) in dry DMF (3 ml) at 0° C. was added NaH (40 mg, 60% dispersion in oil, 1.0 mmol). The mixture was allowed to warm to room temperature over 0.5 h then re-cooled to 0° C. MOMCl (74 mg, 1.1 eq, 0.92 mmol) was added and mixture was allowed to warm to room temperature over 20 hours, concentrated and partitioned between EtOAc and water. The EtOAc phase was dried over anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography (100% hexane to 100% acetone) to afford the title compound 94 (126 mg, 36% yield). MS (m/z): 401.0 (M+H).

Workup

  1. temperaturethen re-cooled to 0° C
  2. temperatureto warm to room temperature over 20 hours
  3. concentrationconcentrated
  4. custompartitioned between EtOAc and water
  5. dry with materialThe EtOAc phase was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by column chromatography (100% hexane to 100% acetone)

Sources & evidence

ORD record
ord-64337613be914cbc8e9686093be004a2
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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