1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 7-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-6-carboxylic acid (2-vinyloxy-ethoxy)-amide

HRID 79081Notes

Reaction equation

HRID 79081 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]2[S:17][N:16]=[CH:15][C:14]=2[CH:13]=[CH:12][C:11]=1[C:19]([OH:21])=O.C(N(C(C)C)CC)(C)C.[CH:31]([O:33][CH2:34][CH2:35][O:36][NH2:37])=[CH2:32].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.C(OCC)(=O)C>[CH:31]([O:33][CH2:34][CH2:35][O:36][NH:37][C:19]([C:11]1[CH:12]=[CH:13][C:14]2[CH:15]=[N:16][S:17][C: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])=[CH2:32]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 575215047-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-6-carboxylic acid

Product 1

HCID 575215067-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-6-carboxylic acid (2-vinyloxy-ethoxy)-amideYield 49.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 7-(2-fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-6-carboxylic acid (328 mg, 0.79 mmol) and diisopropylethylamine (0.41 mL, 2.37 mmol) in DMF (2 mL) were added O-(2-vinyloxy-ethyl)-hydroxylamine (163 mg, 1.58 mmol), EDCI (303 mg, 1.58 mmol) and HOBt (213 mg, 1.58 mmol). The reaction mixture was stirred for 18 hours at room temperature, diluted with ethyl acetate, and washed with water then a saturated aqueous solution of sodium hydrogen carbonate, then brine, before being dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0% to 100%, TBME in cyclohexane) to afford the title compound as a yellow foam (194 mg, 49%). LCMS (method B): RT=3.99 min, [M+H]+=500.

Workup

  1. washwashed with water
  2. dry with materiala saturated aqueous solution of sodium hydrogen carbonate, then brine, before being dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5b079de4d51c49f482d757b2d6dfc764
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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