HCID 59140152, compound → 8-Fluoro-5-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-hydroxy-ethoxy)-amide

HRID 2076208Notes

Reaction equation

HRID 2076208 reaction equation
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:11]=[C:12]([F:28])[C:13]2[N:14]([CH:25]=[N:26][CH:27]=2)[C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=1[F:24])=[O:9])=C>CO>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:11]=[C:12]([F:28])[C:13]2[N:14]([CH:25]=[N:26][CH:27]=2)[C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=1[F:24])=[O:9]

Participants

3

Reactant 1

HCID 59140152HCID 59140152, compound

Product 1

HCID 441379388-Fluoro-5-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-hydroxy-ethoxy)-amideYield 47.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 8-fluoro-5-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-vinyloxy-ethoxy)-amide (200 mg, 0.39 mmol) in methanol (1 mL) was loaded onto an SCX-2 column. The column was washed with methanol (10 mL) then the product was then eluted with ammonia in methanol (20 mL, 2M), the appropriate fractions were 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 were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo to yield the title compound as a white solid (88 mg, 39%). LCMS (Method A): RT=7.71 min, [M+H]+=475. 1H NMR (DMSO-d6): 8.20 (1H, s), 7.60 (1H, s), 7.57 (1H, dd, J=10.73, 1.96 Hz), 7.26 (1H, dd, J=8.43, 1.82 Hz), 6.82 (1H, d, J=11.14 Hz), 6.30 (1H, t, J=8.71 Hz), 3.65 (2H, t, J=4.77 Hz), 3.45 (2H, t, J=4.68 Hz).

Workup

  1. washThe column was washed with methanol (10 mL)
  2. washthe product was then eluted with ammonia in methanol (20 mL, 2M)
  3. concentrationthe appropriate fractions were concentrated in vacuo
  4. dissolutionThe resultant product was dissolved in ethyl acetate (5 mL)
  5. washwashed with aqueous saturated sodium bicarbonate solution (10 mL)
  6. extractionThe aqueous fraction was extracted twice with ethyl acetate (2×10 mL)
  7. washthe combined organics were washed with brine (20 mL)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-edaf372f912d4b2cac67847ae5b11fd1
Source dataset
uspto-grants-2011_04
Patent number
US07923456B2

Reaction notes

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