Methanesulfonic Acid → HCID 178446131, compound

HRID 730007Notes

Reaction equation

HRID 730007 reaction equation
[C:1]([C:5]1[NH:6][C:7]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[F:32])=[C:8]([C:10]2[N:15]=[C:14]3[N:16]([CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:17]([NH2:19])=[N:18][C:13]3=[CH:12][CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:33][S:34]([OH:37])(=[O:36])=[O:35]>CO>[CH3:33][S:34]([OH:37])(=[O:36])=[O:35].[C:1]([C:5]1[NH:6][C:7]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[F:32])=[C:8]([C:10]2[N:15]=[C:14]3[N:16]([CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:17]([NH2:19])=[N:18][C:13]3=[CH:12][CH:11]=2)[N:9]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 178446130HCID 178446130, compound

Product 1

HCID 178446131HCID 178446131, compoundYield 93.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Mix 5-[2-tert-butyl-5-(2,4-difluoro-phenyl)-1H-imidazol-4-yl]-3-(2,2-dimethyl-propyl)-3H-imidazo[4,5-b]pyridin-2-ylamine (11.55 g, 26.33 mmol) in MeOH (150 mL), and then add a solution of methanesulfonic acid (2.53 g, 26.33 mmol) in MeOH (10 mL) dropwise. Stir the resulting reaction mixture at room temperature for 20 minutes, then concentrate under reduced pressure. Slurry the residue in Et2O, then filter and wash with fresh Et2O. Dry the resulting solid in a drying oven at room temperature under house vacuum overnight, then at 80° C. for 1.5 h. Dissolve the salt in MeOH and then treat with NaHCO3 until basic. Extract the resulting solution with EtOAc, dry the combined organics over Na2SO4, filter, then concentrate under reduced pressure. Purify by column chromatography, eluting with neat EtOAc, then 1% of 2N ammonia/MeOH in EtOAc, then 2% of 2N ammonia/MeOH in EtOAc to give 9.38 g of 5-[2-tert-butyl-5-(2,4-difluoro-phenyl)-1H-imidazol-4-yl]-3-(2,2-dimethyl-propyl)-3H-imidazo[4,5-b]pyridin-2-ylamine. Mix 5-[2-tert-butyl-5-(2,4-difluoro-phenyl)-1H-imidazol-4-yl]-3-(2,2-dimethyl-propyl)-3H-imidazo[4,5-b]pyridin-2-ylamine (9.38 g, 21.39 mmol) in anhydrous MeOH (150 mL), and then add a solution of methanesulfonic acid (2.06 g, 21.43 mmol) in MeOH (10 mL) dropwise. Allow the resulting reaction mixture to stir at room temperature for 30 minutes, then concentrate under reduced pressure. Slurry the residue in Et2O, then filter and wash with fresh Et2O. Dry the resulting solid in a drying oven at room temperature under house vacuum for 48 h to give 10.695 g (76% yield) of the title compound as a tan solid.

Workup

  1. customthe resulting reaction mixture
  2. concentrationconcentrate under reduced pressure
  3. filtrationfilter
  4. washwash with fresh Et2O
  5. customDry the resulting solid in a drying oven at room temperature under house vacuum for 48 h

Sources & evidence

ORD record
ord-347af804c8fc473bb33246374324ad37
Source dataset
uspto-grants-2009_09
Patent number
US07582652B2

Reaction notes

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