Potassium Chloride → HCID 86647120, compound

HRID 2391684Notes

Reaction equation

HRID 2391684 reaction equation
ClC1N=CC2N=CN(C3SC(C(OC)=O)=C(O)C=3)C=2C=1.[Cl:21][C:22]1[N:27]=[CH:26][C:25]2[N:28]([C:31]3[S:35][C:34]([C:36]([O:38][CH3:39])=[O:37])=[C:33]([OH:40])[CH:32]=3)[CH:29]=[N:30][C:24]=2[CH:23]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=1[C:55]([F:58])([F:57])[F:56].[Cl-].[K+]>CN(C)C=O>[Cl:21][C:22]1[N:27]=[CH:26][C:25]2[N:28]([C:31]3[S:35][C:34]([C:36]([O:38][CH3:39])=[O:37])=[C:33]([O:40][CH2:48][C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=4[C:55]([F:56])([F:57])[F:58])[CH:32]=3)[CH:29]=[N:30][C:24]=2[CH:23]=1

Participants

7

Reactant 5

HCID 4873Potassium ChlorideHCID 11430Potassium CarbonateHCID 1230571-(Bromomethyl)-2-(trifluoromethyl)benzeneHCID 86647121HCID 86647121, compoundHCID 86647122HCID 86647122, compound

Product 1

HCID 86647120HCID 86647120, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 557 mg of an isomeric mixture of methyl 5-(6-chloro-1H-imidazo[4,5-c]pyridin-1-yl)-3-hydroxythiophene-2-carboxylate and methyl 5-(6-chloro-3H-imidazo[4,5-c]pyridin-3-yl)-3-hydroxythiophene-2-carboxylate (example C2) in 25 ml anhydrous N,N-dimethylformamide were added 248 mg K2CO3 and 428 mg 1-(bromomethyl)-2-(trifluoromethyl)benzene under a nitrogen atmosphere. The reaction mixture was stirred for 12 h at room temperature, poured into 500 ml of ice water, then 40 ml of a saturated solution of KCl were added and the mixture was allowed to stand for 12 h at 0° C. The resulting solid was filtered and washed with water. The filter cake was dissolved in dichloromethane, the organic layer was washed with water, dried with MgSO4 and concentrated under vacuum. The isomeric mixture was separated and purified by flash chromatography [(Silicagel, hexane/ethylacetate (7/3 v/v)]. The separated isomers were crystallized from dichloromethane/hexane to yield compound B3a and compound B3b. The structural assignment of the regioisomers was unequivocally established by two-dimensional 1H NMR experiments (NOESY, COSY).

Workup

  1. waitto stand for 12 h at 0° C
  2. filtrationThe resulting solid was filtered
  3. washwashed with water
  4. dissolutionThe filter cake was dissolved in dichloromethane
  5. washthe organic layer was washed with water
  6. dry with materialdried with MgSO4
  7. concentrationconcentrated under vacuum
  8. customThe isomeric mixture was separated
  9. custompurified by flash chromatography [(Silicagel, hexane/ethylacetate (7/3 v/v)]
  10. customThe separated isomers were crystallized from dichloromethane/hexane
  11. customto yield compound B3a

Sources & evidence

ORD record
ord-af7d8047aaa447ca91cfe2bb3e49648d
Source dataset
uspto-grants-2012_09
Patent number
US08273890B2

Reaction notes

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