1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(2-Fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid (2-vinyloxyethoxy)-amide

HRID 79050Notes

Reaction equation

HRID 79050 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[C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=[C:15]2[C:11]=1[CH:12]=[N:13][NH:14]2.[CH:22]([O:24][CH2:25][CH2:26][O:27][NH2:28])=[CH2:23].CCN=C=NCCCN(C)C.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:18]1[C:10]([NH:9][C:3]2[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=2[F:1])=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)=[O:21])=[CH2:23]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 575215054-(2-Fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid

Product 1

HCID 575231204-(2-Fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid (2-vinyloxyethoxy)-amideYield 71.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(2-fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid (2.14 g, 5.39 mmol) and O-(2-vinyloxy-ethyl)-hydroxylamine (668 mg, 6.50 mmol) in DMF (50 mL) was added EDCI (1.14 g, 5.93 mmol), HOBt (0.80 g, 5.93 mmol) and DIPEA (1 mL, 5.93 mmol). The reaction mixture was stirred at room temperature for 2 hours before being concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (30 mL), washed with aqueous saturated sodium hydrogen carbonate solution (300 mL) and the aqueous fraction extracted with ethyl acetate (2×20 mL). The combined organic extracts were washed with brine (30 mL), dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-100% ethyl acetate in cyclohexane) to yield the title compound as a pale yellow solid (1.85 g, 71%). LCMS (Method B): RT=3.52 min, [M−H]−=481.

Workup

  1. concentrationbefore being concentrated in vacuo
  2. dissolutionThe resultant residue was dissolved in ethyl acetate (30 mL)
  3. washwashed with aqueous saturated sodium hydrogen carbonate solution (300 mL)
  4. extractionthe aqueous fraction extracted with ethyl acetate (2×20 mL)
  5. washThe combined organic extracts were washed with brine (30 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f579e57acc57473bb772bff151c7d055
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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