Hydrochloric Acid → HCID 59140173, compound

HRID 2076210Notes

Reaction equation

HRID 2076210 reaction equation
CC1(C)[O:6][C@@H:5]([CH2:7][O:8][NH:9][C:10]([C:12]2[CH:13]=[C:14]([F:30])[C:15]3[N:16]([CH:27]=[N:28][CH:29]=3)[C:17]=2[NH:18][C:19]2[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=2[F:26])=[O:11])[CH2:4][O:3]1.Cl.O1CCOCC1>CO>[OH:6][C@H:5]([CH2:4][OH:3])[CH2:7][O:8][NH:9][C:10]([C:12]1[CH:13]=[C:14]([F:30])[C:15]2[N:16]([CH:27]=[N:28][CH:29]=2)[C:17]=1[NH:18][C:19]1[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=1[F:26])=[O:11]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 59140134HCID 59140134, compound

Product 1

HCID 59140173HCID 59140173, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 8-fluoro-5-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide (298 mg, 0.55 mmol) in methanol (5 mL) was added hydrochloric acid in dioxane (2 mL, 4N, 8.0 mmol). The reaction mixture was stirred at room temperature for 1 hour then concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (5 mL), washed with aqueous saturated sodium bicarbonate solution (10 mL) and the aqueous fraction extracted twice with ethyl acetate (2×5 mL). The combined organic fractions were washed with brine (10 mL), dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to reverse phase preperative HPLC (10-90% acetonitrile/water 0.1% formic acid, Phenominex gemini PhC6, 5 micron, 250×20 mm). The resultant product was dissolved in ethyl acetate (5 mL) and washed with aqueous saturated sodium bicarbonate solution (10 mL). The aqueous fraction was extracted twice with ethyl acetate (2×10 mL) and the combined organics washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo to yield the title compound as a white solid (83 mg, 30%). LCMS (Method A): RT=7.11 min, [M+H]+=505.

Workup

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe resultant residue was dissolved in ethyl acetate (5 mL)
  3. washwashed with aqueous saturated sodium bicarbonate solution (10 mL)
  4. extractionthe aqueous fraction extracted twice with ethyl acetate (2×5 mL)
  5. washThe combined organic fractions were washed with brine (10 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. dissolutionThe resultant product was dissolved in ethyl acetate (5 mL)
  9. washwashed with aqueous saturated sodium bicarbonate solution (10 mL)
  10. extractionThe aqueous fraction was extracted twice with ethyl acetate (2×10 mL)
  11. washthe combined organics washed with brine (20 mL)
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-aa545a05b0284dc2b5a984fea74dcb43
Source dataset
uspto-grants-2011_04
Patent number
US07923456B2

Reaction notes

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