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

HRID 2067012Notes

Reaction equation

HRID 2067012 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]([CH:21]2[CH2:23][CH2:22]2)=[CH:17][C:16]=1[F:24])=[O:4].[OH-:25].[Na+].[NH2:27][OH:28].[CH3:29][CH2:30]N=C=NCCCN(C)C.[CH:40]1C=CC2N(O)N=NC=2[CH:45]=1>C(OCC)(=O)C>[CH:29]([O:25][CH2:40][CH2:45][O:28][NH:27][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]([CH:21]2[CH2:23][CH2:22]2)=[CH:17][C:16]=1[F:24])=[O:4])=[CH2:30]

Participants

7

Reactant 5

HCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 595651918-(4-Cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester

Product 1

HCID 595652268-(4-Cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amideYield 67.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 8-(4-cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (68 mg, 0.21 mmol) in IMS (2.5 mL) was added a 1.0 M aqueous solution of sodium hydroxide (0.25 mL, 0.25 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 (4 mL). 042-Vinyloxy-ethyl)-hydroxylamine (43 mg, 0.42 mmol), N-N-diisopropylethylamine (0.14 mL, 0.84 mmol), EDCI (81 mg, 0.42 mmol) and HOBt (57 mg, 0.42 mmol) were then added sequentially, before the reaction mixture was stirred for 18 hours at room temperature. The reaction mixture was then diluted with ethyl acetate and washed with water, a saturated aqueous solution of sodium bicarbonate and brine before being dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 5%, methanol in dichloromethane) to afford the title compound as a pale yellow oil (56 mg, 67%). LCMS (method B): RT=3.02 min, [M+H]+=397.

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 materiala saturated aqueous solution of sodium bicarbonate and brine before being dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c134055e6b6648d0af0bd8be6d526e9f
Source dataset
uspto-grants-2012_10
Patent number
US08293763B2

Reaction notes

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