Sodium Hydroxide → 8-(4-Bromo-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amide

HRID 2067023Notes

Reaction equation

HRID 2067023 reaction equation
CO[C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[F:22])=[O:4].[OH-].[Na+].[CH:25]([O:27][CH2:28][CH2:29][O:30][NH2:31])=[CH2:26].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>C(OCC)(=O)C>[CH:25]([O:27][CH2:28][CH2:29][O:30][NH:31][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[F:22])=[O:4])=[CH2:26]

Participants

7

Reactant 5

HCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 595651888-(4-Bromo-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester

Product 1

HCID 595652228-(4-Bromo-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amideYield 65.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 8-(4-bromo-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (50 mg, 0.14 mmol) in IMS (3 mL) was added a 1.0 M aqueous solution of sodium hydroxide (0.3 mL, 0.3 mmol). The reaction mixture was heated at 65° C. for 2 hours and then cooled to room temperature and concentrated in vacuo. The resulting residue was azeotroped with toluene, and then suspended in THF (3 mL). O-(2-Vinyloxy-ethyl)-hydroxylamine (29 mg, 0.28 mmol), N-N-diisopropylethylamine (0.10 mL, 0.56 mmol), EDCI (54 mg, 0.28 mmol) and HOBt (38 mg, 0.28 mmol) were then added sequentially before the reaction mixture was stirred 18 hours at room temperature. The reaction mixture was then diluted with ethyl acetate and washed with water followed by a saturated aqueous solution of sodium bicarbonate and brine. The organic layer was isolated, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 100%, ethyl acetate in dichloromethane) to afford the title compound as a pale yellow oil (40 mg, 65%). LCMS (method B): RT=2.98 min, [M+H]+=435/437.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was azeotroped with toluene
  4. washwashed with water
  5. customThe organic layer was isolated
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-eb11ffde09374577bf25bb2d4054a89d
Source dataset
uspto-grants-2012_10
Patent number
US08293763B2

Reaction notes

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