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

HRID 2067015Notes

Reaction equation

HRID 2067015 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]([S:21][CH3:22])=[CH:17][C:16]=1[F:23])=[O:4].[OH-].[Na+].[CH:26]([O:28][CH2:29][CH2:30][O:31][NH2:32])=[CH2:27].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>C(OCC)(=O)C>[CH:26]([O:28][CH2:29][CH2:30][O:31][NH:32][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]([S:21][CH3:22])=[CH:17][C:16]=1[F:23])=[O:4])=[CH2:27]

Participants

7

Reactant 5

HCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 595652258-(2-Fluoro-4-methylsulfanyl-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester

Product 1

HCID 595652208-(2-Fluoro-4-methylsulfanyl-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amideYield 97%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 8-(2-fluoro-4-methylsulfanyl-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (136 mg, 0.41 mmol) in IMS (10 mL) was added a 1.0 M aqueous solution of sodium hydroxide (0.82 mL, 0.82 mmol). The reaction mixture was heated at 65° C. for 1 hour and then cooled to room temperature and concentrated in vacuo. The resultant residue was azeotroped with toluene, and then suspended in THF (10 mL). O-(2-Vinyloxy-ethyl)-hydroxylamine (84 mg, 0.82 mmol), N-N-diisopropylethylamine (0.28 mL, 1.64 mmol), EDCI (157 mg, 0.82 mmol) and HOBt (111 mg, 0.82 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, dried (Na2SO4), filtered and concentrated. 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 (160 mg, 97%). LCMS (method B): RT=2.91 min, [M+H]+=403.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customThe resultant residue was azeotroped with toluene
  4. washwashed with water
  5. dry with materiala saturated aqueous solution of sodium bicarbonate and brine, dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-9084d4bf7d9146ccb348fd19eb635ecf
Source dataset
uspto-grants-2012_10
Patent number
US08293763B2

Reaction notes

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