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

HRID 2067027Notes

Reaction equation

HRID 2067027 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[Cl: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[Cl: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 59565213HCID 59565213, compound

Product 1

HCID 595652238-(4-Bromo-2-chloro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amideYield 65.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 8-(4-bromo-2-chloro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (271 mg, 0.71 mmol) in IMS (10 mL) was added a 1.0 M aqueous solution of sodium hydroxide (0.8 mL, 0.8 mmol). The reaction mixture was heated at 65° C. for 1 hour and then cooled to room temperature and concentrated in vacuo. The resulting residue was azeotroped with toluene, and then suspended in THF (10 mL). O-(2-Vinyloxy-ethyl)-hydroxylamine (89 mg, 0.87 mmol), N-N-diisopropylethylamine (0.30 mL, 1.73 mmol), EDCI (166 mg, 0.87 mmol) and HOBt (117 mg, 0.87 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 then brine. The isolated organic layer was dried (Na2SO4), filtered and concentrated in vacuo to afford the title compound as a pale yellow solid (210 mg, 65%). LCMS (method B): RT=3.17 min, [M+H]+=451/453.

Workup

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

Sources & evidence

ORD record
ord-41232b0145e54f08bf2f1d3bcf0c8390
Source dataset
uspto-grants-2012_10
Patent number
US08293763B2

Reaction notes

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