1-Hydroxybenzotriazole → 5-(2-Fluoro-4-iodophenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-vinyloxyethoxy)-amide

HRID 2064014Notes

Reaction equation

HRID 2064014 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:15]2[CH:16]=[N:17][CH:18]=[C:14]2[CH:13]=[CH:12][C:11]=1[C:19]([OH:21])=O.[CH:22]([O:24][CH2:25][CH2:26][O:27][NH2:28])=[CH2:23].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:22]([O:24][CH2:25][CH2:26][O:27][NH:28][C:19]([C:11]1[CH:12]=[CH:13][C:14]2[N:15]([CH:16]=[N:17][CH:18]=2)[C:10]=1[NH:9][C:3]1[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=1[F:1])=[O:21])=[CH2:23]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 591401865-(2-Fluoro-4-iodophenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid

Product 1

HCID 591401665-(2-Fluoro-4-iodophenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-vinyloxyethoxy)-amideYield 60.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(2-fluoro-4-iodophenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2.10 g, 5.29 mmol) and O-(2-vinyloxyethyl)-hydroxylamine (0.87 g, 8.46 mmol) in DMF (30 mL) was added EDCI hydrochloride (1.31 g, 6.90 mmol), HOBt (0.93 g, 6.90 mmol) and DIPEA (1.17 mL, 6.90 mmol). The reaction mixture was stirred at room temperature for 5 hours before being concentrated in vacuo. The resultant residue was dissolved in 1:1 tert-butylmethylether:ethyl acetate (20 mL) and aqueous saturated sodium hydrogen carbonate solution (20 mL) was added. The resultant mixture was sonicated until a precipitate formed, the precipitate was collected by filtration and dried in vacuo at 45° C. to yield the title compound as a tan solid (1.55 g, 60%). LCMS (Method B): RT=2.80 min, M+H+=483.

Workup

  1. concentrationbefore being concentrated in vacuo
  2. dissolutionThe resultant residue was dissolved in 1:1 tert-butylmethylether
  3. additionethyl acetate (20 mL) and aqueous saturated sodium hydrogen carbonate solution (20 mL) was added
  4. customThe resultant mixture was sonicated until a precipitate
  5. customformed
  6. filtrationthe precipitate was collected by filtration
  7. customdried in vacuo at 45° C.

Sources & evidence

ORD record
ord-df4c67ba124a4ea6879dcf5bab5e472c
Source dataset
uspto-grants-2012_10
Patent number
US08288408B2

Reaction notes

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