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

HRID 79079Notes

Reaction equation

HRID 79079 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:17]3[S:16][N:15]=[CH:14][C:13]=3[CH:12]=[CH:11][C:10]=2[C:18]([OH:20])=O)=[C:4]([F:21])[CH:3]=1.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:18]([C:10]1[CH:11]=[CH:12][C:13]2[CH:14]=[N:15][S:16][C:17]=2[C:9]=1[NH:8][C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=1[F:21])=[O:20])=[CH2:32]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 670837117-(4-Bromo-2-fluoro-phenylamino)-benzo[d]isothiazole-6-carboxylic acid

Product 1

HCID 866562527-(4-Bromo-2-fluoro-phenylamino)-benzo[d]isothiazole-6-carboxylic acid (2-vinyloxy-ethoxy)-amideYield 37%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 7-(4-bromo-2-fluoro-phenylamino)-benzo[d]isothiazole-6-carboxylic acid (210 mg, 0.57 mmol) and diisopropylethylamine (0.29 mL, 1.71 mmol) in DMF (2 mL) were added O-(2-vinyloxy-ethyl)-hydroxylamine (117 mg, 1.14 mmol), EDCI (220 mg, 1.14 mmol) and HOBt (154 mg, 1.14 mmol). The reaction mixture was stirred for 18 hours at room temperature, diluted with ethyl acetate and washed with water, 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 oil (95 mg, 37%). LCMS (method B): RT=3.90 min, [M+H]+=452/454.

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-07c2a96c46824c2896fc29d4a5de91a5
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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